Distinct Responses Research Articles

Sex-specific nociceptor modulation of the apical periodontitis transcriptome.

Introduction: Apical periodontitis (AP) is a painful disease that develops quickly following dental infections and is primarily characterized by robust inflammation surrounding the tissues of the affected tooth, resulting in disruption of bone homeostasis and periradicular bone loss. Moreover, there are distinct clinical presentations, symptoms, and responses to AP treatment between male and female subjects, creating a desperate need to further understand the sex-specific mechanisms of AP. Methods: With the growing evidence that nociceptors modulate AP development, we utilized RNA sequencing in nociceptor-ablated (Nav1.8 cre+/-, diphtheria toxin Alox+/-) transgenic mice to study the nociceptor regulation of the periapical lesion transcriptome using a rodent model of AP in female mice over 14days. Results: Overall, we found that female mice exhibit unique patterns of differentially expressed genes throughout AP infection compared to male mice and that the expression of these genes is regulated by nociceptors. Additionally, nociceptor ablation results in a more significant enrichment of biological processes related to immune responses earlier compared to cre-control (Nav1.8 cre+/-) females and greater expression of genes involved in inflammatory processes and osteolytic activity. Discussion: Therefore, while nociceptor ablation augments inflammatory and bone resorption responses in both males and females in a mouse model of AP, transcriptomic analyses demonstrate that the mechanisms through which nociceptors modulate AP are distinct between sexes. These studies will provide the foundation needed to study further mechanisms of sex differences in AP, an area with a desperate need for investigation to treat current AP patients. Understanding these mechanisms can ultimately inform treatment options to alleviate suffering for millions of patients suffering from AP.

Phosphorylation of Arabidopsis UVR8 photoreceptor modulates protein interactions and responses to UV-B radiation

Exposure of plants to ultraviolet-B (UV-B) radiation initiates transcriptional responses that modify metabolism, physiology and development to enhance viability in sunlight. Many of these regulatory responses to UV-B radiation are mediated by the photoreceptor UV RESISTANCE LOCUS 8 (UVR8). Following photoreception, UVR8 interacts directly with multiple proteins to regulate gene expression, but the mechanisms that control differential protein binding to initiate distinct responses are unknown. Here we show that UVR8 is phosphorylated at several sites and that UV-B stimulates phosphorylation at Serine 402. Site-directed mutagenesis to mimic Serine 402 phosphorylation promotes binding of UVR8 to REPRESSOR OF UV-B PHOTOMORPHOGENESIS (RUP) proteins, which negatively regulate UVR8 action. Complementation of the uvr8 mutant with phosphonull or phosphomimetic variants suggests that phosphorylation of Serine 402 modifies UVR8 activity and promotes flavonoid biosynthesis, a key UV-B-stimulated response that enhances plant protection and crop nutritional quality. This research provides a basis to understand how UVR8 interacts differentially with effector proteins to regulate plant responses to UV-B radiation.

Emotional responses to climate change in Norway and Ireland: a validation of the Inventory of Climate Emotions (ICE) in two European countries and an inspection of its nomological span.

There is an increasing research interest in emotional responses to climate change and their role in climate action and psycho-social impacts of climate change. At the same time, emotional experience of climate change is multidimensional and influenced by a variety of factors, including the local cultural context. Here, we contribute to the scientific debate about this topic with original quality-controlled data from the general populations in Norway (N = 491) and Ireland (N = 485). We investigate the cross-cultural validity and the nomological span of eight distinct emotional responses to climate change - climate anger, climate contempt, climate enthusiasm, climate powerlessness, climate guilt, climate isolation, climate anxiety, and climate sorrow - measured using the recently introduced Inventory of Climate Emotions. We first validate the 8-factor structure of the Norwegian and English language versions of the ICE. Subsequently, we demonstrate a high degree of cross-cultural measurement invariance for these eight climate emotions. Finally, we explore the relationships between these emotional responses and a range of theoretically relevant variables. In this final step, we show that climate emotions are differentially linked to climate change perceptions, support for mitigation policies, socio-demographic factors, feelings of loneliness and alienation, environmental activism, and the willingness to prioritize the natural environment over one's immediate self-interests. Some of these links are also differentiated by the cultural context. This research presents further evidence for the structural, cross-cultural, and concurrent validity of climate emotions as postulated in the ICE framework. Moreover, it provides tools in the form of validated Norwegian and English language versions of the ICE, the complete R code for the validation analysis, as well as an informed basis for cross-cultural research on emotional responses to climate change.

FRET-Based Host-Guest Supramolecular Probe for On-Site and Broad-Spectrum Detection of Pyrethroids in the Environment.

The massive use of pyrethroid pesticides in agriculture has brought growing concerns about food safety due to their several harmful effects on human health, especially through the accumulation of the food chain. To date, most of the available analytical methods for pyrethroids still suffer from insufficient detection universality, complicated sample pretreatment, and detection processes, which severely limit their practical applications. Herein, a novel Förster resonance energy transfer (FRET)-assisted host-guest supramolecular nanoassembly is reported, for the first time, successfully realizing ratiometric fluorescent detection of pyrethroids in real samples through the indicator displacement assay (IDA) mechanism. This method is capable of detecting a broad spectrum of pyrethroids, including bifenthrin, cyfluthrin, cypermethrin, deltamethrin, etofenprox, fenvalerate, and permethrin, with ultrahigh detection sensitivity, great selectivity, high anti-interference ability, and, in particular, distinct emission color response from red to green. Such a large chromatic response makes this method available for fast and on-site detection of pyrethroids in real samples with the aid of several simple portable analytical apparatuses.

Electric field modulation of ERK dynamics shows dependency on waveform and timing

Different exogenous electric fields (EF) can guide cell migration, disrupt proliferation, and program cell development. Studies have shown that many of these processes were initiated at the cell membrane, but the mechanism has been unclear, especially for conventionally non-excitable cells. In this study, we focus on the electrostatic aspects of EF coupling with the cell membrane by eliminating Faradaic processes using dielectric-coated microelectrodes. Our data unveil a distinctive biphasic response of the ERK signaling pathway of epithelial cells (MCF10A) to alternate current (AC) EF. The ERK signal exhibits both inhibition and activation phases, with the former triggered by a lower threshold of AC EF, featuring a swifter peaking time and briefer refractory periods than the later-occurring activation phase, induced at a higher threshold. Interestingly, the biphasic ERK responses are sensitive to the waveform and timing of EF stimulation pulses, depicting the characteristics of electrostatic and dissipative interactions. Blocker tests and correlated changes of active Ras on the cell membrane with ERK signals indicated that both EGFR and Ras were involved in the rich ERK dynamics induced by EF. We propose that the frequency-dependent dielectric relaxation process could be an important mechanism to couple EF energy to the cell membrane region and modulate membrane protein-initiated signaling pathways, which can be further explored to precisely control cell behavior and fate with high temporal and spatial resolution.

Rearrangement of GUV-confined actin networks in response to micropipette aspiration.

Although diverse actin network architectures found inside the cell have been individually reconstituted outside of the cell, how different types of actin architectures reorganize under applied forces is not entirely understood. Recently, bottom-up reconstitution has enabled studies where dynamic and phenotypic characteristics of various actin networks can be recreated in an isolated cell-like environment. Here, by creating a giant unilamellar vesicle (GUV)-based cell model encapsulating actin networks, we investigate how actin networks rearrange in response to localized stresses applied by micropipette aspiration. We reconstitute actin bundles and branched bundles in GUVs separately and mechanically perturb them. Interestingly, we find that, when aspirated, protrusive actin bundles that are otherwise randomly oriented in the GUV lumen collapse and align along the axis of the micropipette. However, when branched bundles are aspirated, the network remains intact and outside of the pipette while the GUV membrane is aspirated into the micropipette. These results reveal distinct responses in the rearrangement of actin networks in a network architecture-dependent manner when subjected to physical forces.

Investigating odonates' response to climate change in Great Britain: A tale of two strategies

AbstractAimSpecies are largely thought to maintain broadly static niches over time, an assumption underpinning much theoretical ecology including the implementation of ecological models to project species' current and future distributions. Here, we assess niche conservatism in odonates in Great Britain over the past six decades by simultaneously quantifying changes in species geographic distribution and evaluating temporal trends in species realised climatic niche.LocationGreat Britain.MethodsDistributional changes were assessed by calculating changes in species distribution centres and deriving occupancy trends. Changes in climatic niches were assessed using a principal component analysis to quantify niche overlap, using information on both climate averages and extremes.ResultsWe show that dragonflies and damselflies displayed distinct responses to changing climatic conditions. Dragonflies shifting to higher latitudes maintained, on average, greater consistency in their climatic niches, providing evidence for climate tracking. Greater climate niche flexibility and increased occupancy over time, on the other hand, were more common in damselflies.Main ConclusionsWe unveil evidence for climatic niche divergence in damselflies on a national scale, casting doubt on the relevance of species distribution models for predicting the impacts of climate change on this, and potentially other, groups of species. More broadly, our results call for more multi‐species temporal comparisons of spatial distributions and climate niches during recent periods of changes in climatic conditions to improve our ability to contrast species' vulnerability risk to the ongoing climate crisis.

How national models of solidarity shaped public support for policy responses to the COVID-19 crisis in 2020–2021

How do national models of solidarity shape public support for distinctive policy responses to social and economic crises, such as the COVID-19 pandemic? We analyze American and German policy responses from March 2020 to June 2021 across a number of economic and social policy domains and identify path-dependent institutional contingencies in both countries despite the same crisis experience. Drawing from 10 different sources of public opinion data, we then triangulate the pandemic's effects on public support for individualized and collectively oriented policy responses. Aside from emotional rally-to-the-flag effects, the policy-specific public reactions are consistent with institutional and normative predicates of the two political economies: the German public seems to be supportive of aggressive policies to combat inequality, though in ways that privilege established social collectivities and groups, whereas in the U.S., we only see moderate evidence of support for time-limited and individually-focused measures designed to remain in place only for the duration of the crisis.

Autumnal Potassium Induced Modulations in Plant Osmoprotectant Substances, Nutrient Stoichiometry and Precision Sustainable Seedling Cultivation in Parashorea chinensis

Parashorea chinensis, an endemic tree species in China’s tropical rainforests, holds ecological and economic importance. Challenges like low resistance, poor quality, and low survival rates hinder its successful cultivation. This study explores the potential of autumn potassium fertilization on Parashorea seedlings from two provenances (Napo and Tianyang). The treatments included no fertilizer (CK-1), a single application of 160 mg K·plant−1 (CK-2), and various potassium levels K1, K2, K3, K4, K5, and K6 (corresponding to 0, 40, 80, 160, 320, and 640 mg·K·plant−1, respectively) combined with nitrogen (200 mg·plant−1) and phosphorus (80 mg·plant−1) fertilization. The findings indicate that autumn potassium application, in conjunction with nitrogen (N) and phosphorus (P) fertilization, significantly enhances seedling height and biomass in both provenances, resulting in an average increase of 101% and 89% under the K4 treatment compared to CK-1 and CK-2, comparatively. Both Napo and Tianyang provenances exhibited distinct responses in photosynthetic rate (2.70 μmol·m−2·s−1 and 1.97 μmol·m−2·s−1, respectively) and stomatal conductance (0.042 mol·m−2·s−1 and 0.029 mol·m−2·s−1, respectively) to the K4 treatment, which proved most effective. The chlorophyll content was significantly higher for Napo provenance with the K3 treatment (74.31%, 58.99%), while for Tianyang, it was higher with the K4 treatment (41.48%, 17.36%), compared to CK-1 and CK-2, respectively. Antioxidant enzymes activity, osmoregulatory capacity, and malondialdehyde content all exhibited variations with potassium application levels, with the K4 treatment offering significant benefits. In Napo provenance, lignin (199.82 mg·g−1) and cellulose (252.38 mg·g−1) peaked at K4, while Tianyang exhibited variation, higher lignin (184.25 mg·g−1) at K3, and cellulose (257.73 mg·g−1) at K4. Nutrient content analysis demonstrates that the K4 treatment enhances nutrient absorption and storage, increasing total N (21.56 mg·kg−1), P (4.69 mg·kg−1), and K (13.49 mg·kg−1) content. A comprehensive analysis reveals that the K4 treatment yields the highest quality scores (1.87, 1.85) and membership values (0.82, 0.68) for both Napo and Tianyang seedlings, with Napo seedlings outperforming their Tianyang provenance. Thus, treatment K4 underscores the effectiveness of autumn potassium applications for robust seedling cultivation and adaptation, offering valuable insights for sustainable cultivation practices.

Microscopic Origins of the Distinct Mechanical Response of ABA and ABC Block Copolymer Nanostructures.

It has been commonly believed that the ordered thermoplastic elastomers formed by the ABC triblock copolymer should have better mechanical performance than that by the ABA counterpart due to the higher bridging fraction. However, the thermoplastic elastomer of ABA was often observed to perform better than that of ABC. To compare the performance of two kinds of thermoplastic elastomers and unveil the underlying microscopic mechanism, we have calculated their stress-strain curves using coarse-grained molecular dynamics simulations in conjunction with self-consistent field theory. It is revealed that the stretching degree of the bridging blocks and the network connectivity play important roles in determining the mechanical properties in addition to the bridging fraction. The higher degree in the stretching of bridging blocks and network connectivity of the structure formed by the ABA triblock copolymer enables its superior mechanical performance over the ABC block copolymer.

In vitro propagation of Indonesian stevia (Stevia rebaudiana) genotype using axenic nodal segments.

The high industrial demand for Stevia cultivation (Stevia rebaudiana) has increased due to its high stevioside content derived from the leaves. However, the low germination rate makes the cultivation of the plant become the main obstacle. Therefore, an efficient cultivation technique is required. This present work aims to analyze the effect of five combinations of Kinetin (Kin) and benzyladenine (BA) on stevia micropropagation using nodal segment explants. The micropropagation of stevia was performed using Murashige and Skoog (MS) medium supplemented with BA and Kin. We analyzed different organogenesis and callogenesis responses. In addition, the number of shoots and root formed during in vitro culture were also observed. Our results demonstrated that all treatments with Kin, both alone and in combination with BA, resulted in the development of callus on all nodal segment explants. Explants treated in MS with 1mgL-1 BA exhibited the best average of shoot number (36.27). In contrast, the treatment without PGR resulted in the best root formation (2.6). The overall results suggested that different combination of BA and Kin resulted in distinct organogenesis responses, where 1mgL-1 of BA was potentially used for boosting the number of shoots in micropropagation of stevia accession Mini.

Evolutionary Analysis of Six Gene Families Part of the Reactive Oxygen Species (ROS) Gene Network in Three Brassicaceae Species.

Climate change is expected to intensify the occurrence of abiotic stress in plants, such as hypoxia and salt stresses, leading to the production of reactive oxygen species (ROS), which need to be effectively managed by various oxido-reductases encoded by the so-called ROS gene network. Here, we studied six oxido-reductases families in three Brassicaceae species, Arabidopsis thaliana as well as Nasturtium officinale and Eutrema salsugineum, which are adapted to hypoxia and salt stress, respectively. Using available and new genomic data, we performed a phylogenomic analysis and compared RNA-seq data to study genomic and transcriptomic adaptations. This comprehensive approach allowed for the gaining of insights into the impact of the adaptation to saline or hypoxia conditions on genome organization (gene gains and losses) and transcriptional regulation. Notably, the comparison of the N. officinale and E. salsugineum genomes to that of A. thaliana highlighted changes in the distribution of ohnologs and homologs, particularly affecting class III peroxidase genes (CIII Prxs). These changes were specific to each gene, to gene families subjected to duplication events and to each species, suggesting distinct evolutionary responses. The analysis of transcriptomic data has allowed for the identification of genes related to stress responses in A. thaliana, and, conversely, to adaptation in N. officinale and E. salsugineum.

Warm Arctic–Cold Eurasia pattern driven by atmospheric blocking in models and observations

In recent decades, Arctic-amplified warming and sea-ice loss coincided with a prolonged wintertime Eurasian cooling trend. This observed Warm Arctic–Cold Eurasia pattern has occasionally been attributed to sea-ice forced changes in the midlatitude atmospheric circulation, implying an anthropogenic cause. However, comprehensive climate change simulations do not produce Eurasian cooling, instead suggesting a role for unforced atmospheric variability. This study seeks to clarify the source of this model-observation discrepancy by developing a statistical approach that enables direct comparison of Arctic-midlatitude interactions. In both historical simulations and observations, we first identify Ural blocking as the primary causal driver of sea ice, temperature, and circulation anomalies consistent with the Warm Arctic–Cold Eurasia pattern. Next, we quantify distinct transient responses to this Ural blocking, which explain the model-observation discrepancy in historical Eurasian temperature. Observed 1988–2012 Eurasian cooling occurs in response to a pronounced positive trend in Ural sea-level pressure, temporarily masking long-term midlatitude warming. This observed sea-level pressure trend lies at the outer edge of simulated variability in a fully coupled large ensemble, where smaller sea-level pressure trends have little impact on the ensemble mean temperature trend over Eurasia. Accounting for these differences bring observed and simulated trends into remarkable agreement. Finally, we quantify the influence of sea-ice loss on the magnitude of the observed Ural sea-level pressure trend, an effect that is absent in historical simulations. These results illustrate that sea-ice loss and tropospheric variability can both play a role in producing Eurasian cooling. Furthermore, by conducting a direct model-observation comparison, we reveal a key difference in the causal structures characterizing the Warm Arctic–Cold Eurasia Pattern, which will guide ongoing efforts to explain the lack of Eurasian cooling in climate change simulations.

Ecotoxicological consequences of polystyrene naturally leached in pure, fresh, and saltwater: lethal and nonlethal toxicological responses in Daphnia magna and Artemia salina

Polystyrene is widely used in disposable products and is now a ubiquitous plastic pollutant in aquatic environments, where it degrades into smaller particles that leach potentially toxic chemicals. However, knowledge regarding the impacts of plastic leachates remains limited. This study investigates the lethal and nonlethal effects of polystyrene leachate on two ecologically significant aquatic organisms, Daphnia magna (water flea) and Artemia salina (brine shrimp). Polystyrene leachates were prepared in seawater, freshwater, and sterile, pure water by incubating the material in each of the media under natural conditions for six months. D. magna and A. salina were exposed to varying concentrations of the leachates under controlled laboratory conditions, monitoring their survival, as well as measuring reactive oxygen species and antioxidant responses as superoxide dismutase and catalase activity. The data show that A. salina was more significantly affected with higher mortality observed at lower leachate concentrations, potentially linked to seawater enhancing the leaching of toxic additives. Moreover, at non-lethal concentrations, the antioxidative responses maintained homeostasis in both organisms. Considering the current reported microplastic concentrations in the aquatics and the adequate antioxidative response, leachate from plastic potentially does not pose a severe threat to these organisms. Nevertheless, hydrological characteristics of waterbodies may cause microplastic hotspots, which could significantly concentrate plastics and thus their leachates, necessitating action to reduce the current microplastic pollution level and avoid future surges. This study highlights the ecological significance of polystyrene pollution, emphasizing the need for more comprehensive regulatory measures and the development of sustainable alternatives to polystyrene-based products. The distinct responses of D. magna and A. salina imply that the impact of plastic pollution varies among species, necessitating further research to elucidate broader ecological consequences. Understanding how polystyrene leachate affects keystone species provides crucial insights into the overall implications for aquatic ecosystems.

The impact of selective HDAC inhibitors on the transcriptome of early mouse embryos

BackgroundHistone acetylation, which is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs), plays a crucial role in the control of gene expression. HDAC inhibitors (HDACi) have shown potential in cancer therapy; however, the specific roles of HDACs in early embryos remain unclear. Moreover, although some pan-HDACi have been used to maintain cellular undifferentiated states in early embryos, the specific mechanisms underlying their effects remain unknown. Thus, there remains a significant knowledge gap regarding the application of selective HDACi in early embryos.ResultsTo address this gap, we treated early embryos with two selective HDACi (MGCD0103 and T247). Subsequently, we collected and analyzed their transcriptome data at different developmental stages. Our findings unveiled a significant effect of HDACi treatment during the crucial 2-cell stage of zygotes, leading to a delay in embryonic development after T247 and an arrest at 2-cell stage after MGCD0103 administration. Furthermore, we elucidated the regulatory targets underlying this arrested embryonic development, which pinpointed the G2/M phase as the potential period of embryonic development arrest caused by MGCD0103. Moreover, our investigation provided a comprehensive profile of the biological processes that are affected by HDACi, with their main effects being predominantly localized in four aspects of zygotic gene activation (ZGA): RNA splicing, cell cycle regulation, autophagy, and transcription factor regulation. By exploring the transcriptional regulation and epigenetic features of the genes affected by HDACi, we made inferences regarding the potential main pathways via which HDACs affect gene expression in early embryos. Notably, Hdac7 exhibited a distinct response, highlighting its potential as a key player in early embryonic development.ConclusionsOur study conducted a comprehensive analysis of the effects of HDACi on early embryonic development at the transcriptional level. The results demonstrated that HDACi significantly affected ZGA in embryos, elucidated the distinct actions of various selective HDACi, and identified specific biological pathways and mechanisms via which these inhibitors modulated early embryonic development.

Switch from fight-flight to freeze-hide: The impacts of severe stress and brain serotonin on behavioral adaptations in flatfish.

Animals often experience changes in their environment that can be perceived as stressful. Previous evidence indicates that different individuals may have distinct stress responses. The role of serotonin (5-HT) in stress adaptation is well established, but its relationship with different defense strategies and the persistence of physiological and behavioral responses in different individuals during repeated acute stress remain unclear. In this study, using olive flounder (Paralichthys olivaceus) as a model, we analyzed the relationship between boldness and neurotransmitter 5-HT activity. We found that 5-HT suppression with 5-HT synthesis inhibitor p-chlorophenylalanine (pCPA) and 5-HT receptor subtype 1A (5-HT1A) antagonist WAY-100635 increased their oxygen consumption rates and the boldness of shy individuals. We determined the metabolic and behavioral changes in bold and shy individuals to repeated acute stress. The results suggest that bold individuals switch on passive "energy-saving" personality by changing their defense behavior from "fight-flight" to "freeze-hide" during a threat encounter, which manifests high behavioral plasticity. Both behavioral types decreased their spontaneous activity levels, which were also strengthened by limiting metabolic rate. Interestingly, treatment with pCPA and WAY-100635 before stress procedure attenuated stress and increased the boldness across diverse behavioral types. This study provides the initial empirical evidence of how perception of stress impacts both individual defense behavior and personality in this species. These findings can enhance our comprehension of individual variability and behavioral plasticity in animals, thereby improving our ability to develop effective adaptive management strategies.

Simultaneous Electrochemical Detection of Multiple Bacterial Species Using Metal-Organic Nanohybrids.

Organic metallic nanohybrids (NHs), in which many small metal nanoparticles are encapsulated within a conductive polymer matrix, are useful as sensitive electrochemical labels because the constituents produce characteristic oxidation current responses. Gold NHs, consisting of gold nanoparticles and poly(m-toluidine), and copper NHs, consisting of copper nanoparticles and polyaniline, did not interfere with each other in terms of the electrochemical signals obtained on the same electrode. Antibodies were introduced into these NHs to function as electrochemical labels for targeting specific bacteria. Electrochemical measurements using screen-printed electrodes dry-fixed with NH-labeled bacterial cells enabled the estimation of bacterial species and number within minutes, based on the distinct current response of the labels. Our proposed method achieved simultaneous detection of enterohemorrhagic Escherichia coli and Staphylococcus aureus in a real sample. These NHs will be powerful tools as electrochemical labels and are expected to be useful for rapid testing in food and drug-related manufacturing sites.

Analysis of multiple biomarkers revealed the size matters of Cu particles for barley response under foliar exposure

The impact of particle size of engineered nanoparticles (ENPs) on plant response has marginally been investigated under the foliar application so far. Concerning the significance of particle diameter for their properties and interaction with plants, the effect of size should be considered in the analysis of the effect of micronutrient-based ENPs on plants. It is of particular importance for ENPs containing Cu due to plants needing a relatively low amount of this element, thus there is a risk of overdosing during application as a fertilizer or pesticide. Here, we examined the biochemical and transcriptional response of barley (Hordeum vulgare L.) to Cu nanoparticles (nano-Cu) with different diameters (25 nm, 50 nm, 70 nm), microparticles (micro-Cu), and chelated Cu (EDTA-Cu). The plants suffering from Cu deficiency were foliar sprayed with Cu compounds at 1000 mg/L during the tillering stage. 1- and 7-day plants were analyzed in terms of biomass, Cu content, the activity of enzymes involved with antioxidant response, the content of low molecular weight compounds, and the expression of genes regulated metal homeostasis, aquaporins, and defense. The results showed that the Cu leaf level was differentiated over time and after 7 days it was higher under exposure to the smallest nano-Cu than other particulate Cu. Regardless of the duration of exposure, the Cu content was highest in plants treated with Cu-EDTA. The cluster analysis of all markers revealed a clear distinct response to the smallest nano-Cu and other particulate and ionic treatments. The bigger nano-Cu, depending on the markers, caused the medium effects between the nano-Cu 25 nm and micro-Cu and Cu-EDTA. The found size thresholds at the nanoscale will be useful for the fabrication of safe-by-design agrochemicals to provide crop security and attenuate environmental impact.

Modeling of senescence-related chemoresistance in ovarian cancer using data analysis and patient-derived organoids.

Ovarian cancer (OC) is a malignant tumor associated with poor prognosis owing to its susceptibility to chemoresistance. Cellular senescence, an irreversible biological state, is intricately linked to chemoresistance in cancer treatment. We developed a senescence-related gene signature for prognostic prediction and evaluated personalized treatment in patients with OC. We acquired the clinical and RNA-seq data of OC patients from The Cancer Genome Atlas and identified a senescence-related prognostic gene set through differential and cox regression analysis in distinct chemotherapy response groups. A prognostic senescence-related signature was developed and validated by OC patient-derived-organoids (PDOs). We leveraged gene set enrichment analysis (GSEA) and ESTIMATE to unravel the potential functions and immune landscape of the model. Moreover, we explored the correlation between risk scores and potential chemotherapeutic agents. After confirming the congruence between organoids and tumor tissues through immunohistochemistry, we measured the IC50 of cisplatin in PDOs using the ATP activity assay, categorized by resistance and sensitivity to the drug. We also investigated the expression patterns of model genes across different groups. We got 2740 differentially expressed genes between two chemotherapy response groups including 43 senescence-related genes. Model prognostic genes were yielded through univariate cox analysis, and multifactorial cox analysis. Our work culminated in a senescence-related prognostic model based on the expression of SGK1 and VEGFA. Simultaneously, we successfully constructed and propagated three OC PDOs for drug screening. PCR and WB from PDOs affirmed consistent expression trends as those of our model genes derived from comprehensive data analysis. Specifically, SGK1 exhibited heightened expression in cisplatin-resistant OC organoids, while VEGFA manifested elevated expression in the sensitive group (P<0.05). Intriguingly, GSEA results unveiled the enrichment of model genes in the PPAR signaling pathway, pivotal regulator in chemoresistance and tumorigenesis. This revelation prompted the identification of potential beneficial drugs for patients with a high-risk score, including gemcitabine, dabrafenib, epirubicin, oxaliplatin, olaparib, teniposide, ribociclib, topotecan, venetoclax. Through the formulation of a senescence-related signature comprising SGK1 and VEGFA, we established a promising tool for prognosticating chemotherapy reactions, predicting outcomes, and steering therapeutic strategies. Patients with high VEGFA and low SGK1 expression levels exhibit heightened sensitivity to chemotherapy.

Evaluation of enterovirus concentration, species identification, and cerebrospinal fluid parameters in patients of different ages with aseptic meningitis in São Paulo, Brazil.

Human enteroviruses (EV) are the most common cause of aseptic meningitis worldwide. Data on EV viral load in cerebrospinal fluid (CSF) and related epidemiological studies are scarce in Brazil. This study investigated the influence of EV viral load on CSF parameters, as well as identifying the involved species. CSF samples were collected in 2018-2019 from 140 individuals at The Hospital das Clínicas, São Paulo. The EV viral load was determined usingreal-time quantitative polymerase chain reaction,while EV species were identified by5'UTR region sequencing.Median viral load was 5.72 log10 copies/mL and did not differ by subjects'age and EV species. Pleocytosis was observed in 94.3% of cases, with the highest white blood cell (WBC) counts in younger individuals. Viral load and WBC count were correlated in children (p = 0.0172). Elevated lactate levels were observed in 60% of cases and correlated with the viral load in preteen-teenagers (p = 0.0120) and adults (p = 0.0184). Most individuals had normal total protein levels (70.7%), with higher in preteen-teenagers and adults (p < 0.0001). By sequencing, 8.2% were identified as EV species A and 91.8% as species B. Age-specific variations in CSF characteristics suggest distinct inflammatory responses in each group.