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Once again, an old-time concept once dismissed has now been shown as valid with modern research. Natural health clinicians have long recognized that digestive disturbances greatly contribute to chronic disease. To the roles in maldigestion of hypochlorhydria and dysbiosis we can now add pancreatic exocrine insufficiency (EPI). At least 20% of the population aged >50 to 75 years with no diagnosed disease has EPI, with higher percentages found in those with disease, especially diabetes. This editorial explores the prevalence of EPI and its diagnosis, causes, and interventions.
DNA study reveals hidden biodiversity off Brazil-and raises alarm over oil exploration.
Lichens in general and members of the genus Cladonia in particular are known for their repertoire of chemical substances. These substances have been attributed various roles, including a role in the defence against herbivores. Unsurprisingly, Cladonia species share habitats with many small invertebrates, like mites. Mites have been suggested to regularly feed on lichens, with potential detrimental effects for the lichen. Here we tested the feeding preferences of two oribatid mite species (Carabodes areolatus and C. marginatus) for three members of the lichen genus Cladonia. Cladonia coniocraea, C. norvegica and C. rubrotincta have similar morphology, ecology, and they regularly share their habitats with the selected mites, but produce different chemical compounds (barbatic acid in Cladonia norvegica, barbatic and rhodocladonic acids in Cladonia rubrotincta, and the fumarprotocetraric acid complex in Cladonia coniocraea), some of which are considered to have antiherbivore properties. Our experiments conducted over a period of 14 days revealed that none of the three lichens was rejected as a food source. When given a choice between two different lichens, mites prefer C. rubrotincta over C. norvegica, but feed to a similar extent on C. coniocraea and C. rubrotincta. In experiments only with C. rubrotincta, which produces the red chemical compound rhodocladonic acid, a substance with suggested antiherbivore activity, mites surprisingly seem to prefer red-pigmented over unpigmented tissue.
In dairy production, Hermetia illucens oil (HIO) could represent a more sustainable energy source than oil palm products, but no in vivo information is available on the effects of this strategy on ruminal biohydrogenation and microbial-derived lipids [odd- and branched-chain fatty acids (FA) and dimethyl acetals (DMA)]. To address this knowledge gap, two balanced groups of 13 Valdostana Red Pied cows were fed a 70:30 forage-to-concentrate ratio diet, differing only for its supplemental lipid source: fractionated palm oil (FPO) or HIO (3.4% of concentrate dry matter). At the beginning and after 50 days of treatments, ruminal fluid was collected for a detailed characterization of lipids. Ruminal fluid of HIO cows showed a 25% decrease in total FA content relative to FPO, which might be explained by extensive ruminal disappearance of 12:0 (the main FA in HIO). Dietary HIO slightly reduced biohydrogenation completeness (-1.6%; P = 0.014) without favoring alterations that lead to the trans-10 pathway (e.g., without increasing trans-10 18:1/trans-11 18:1 ratio; P = 0.719). Just a few changes in ruminal FA composition appear to be explained by differences in FA intake (e.g., in 12:0 and 16:0; P < 0.001), whereas most variations would probably derive from an indirect effect of HIO promoting minor pathways of biohydrogenation and alternative metabolic processes, as supported by increases (P < 0.05) in the proportion of oxo-18:0 isomers and most BH intermediates with at least one double bond in Δ12 to Δ16 positions, compared with FPO. Changes in odd- and branched-chain FA and in DMA support that HIO affects ruminal FA profile through potential variations in ruminal microbial composition. The relative proportion of individual DMA was also modified, whereas total DMA content was not affected (P = 0.146). Overall, the minor effects of HIO on biohydrogenation, compared with FPO, supports the use of this alternative lipid source in dairy cow feeding. The oil extracted from black soldier fly (Hermetia illucens) larvae has recently emerged as a sustainable and innovative feed ingredient. Conventional fats are often included in the diets of dairy cows, but some of them are associated with negative environmental impact, such as those derived from oil palm cultivation. The aim of this study was to characterize the effects of replacing palm oil by black soldier fly oil on the lipid metabolism in the rumen of cows, which is a key aspect determining the digestion and subsequent utilization of lipids for milk fat production. Surprisingly, we observed a decrease in total fat content in the ruminal fluid of cows fed the black soldier fly oil, which was associated with an extensive disappearance of lauric acid (the most abundant fatty acid in the insect oil). The study of lipids that represent biomarkers of ruminal microbiota suggest possible changes in this microbial community, which may derive, at least in part, from the antimicrobial effect of lauric acid. Overall, our results suggest that H. illucens oil can be used in dairy cow diets without detrimental effects on ruminal lipid metabolism, as we observed only minimal changes in metabolic pathways compared to the use of palm oil, thus supporting its potential use as a sustainable feed ingredient.
Boronic acids react reversibly with diols to form boronic ester derivatives, a process that can be used as a protecting group in multistep synthesis. Boronic ester formation is also an example of dynamic covalent chemistry that can be used for diverse applications, including polyol recognition, dynamic soft materials, and controlled drug release. Somewhat surprisingly, only limited quantitative structure-function relationships for boronic stability with different diols are available, with the consequence that it has been difficult to choose or design optimal reactivity, whether for multistep synthesis or for dynamic covalent applications. Here we report the first systematic study of a family of 1,2-diols that enable a series of boronic esters with tunable hydrolytic behavior and simple one-pot formation. Across a panel of aryl, heteroaryl, and bioactive boronic acids, we found that diol structure, electronics, and pH can be used together to modulate hydrolysis rates over a broad range while maintaining silica compatibility. This work establishes a practical dataset for rationally selecting boronic ester protecting groups to achieve predictable, mild, and temporally controlled access to free boronic acids in water under biocompatible conditions, and also provides a simple synthetic solution to some longstanding challenges in the preparation of complex boronic acids.
Diffusion Transformers (DiT) have become the dominant methods in image and video generation yet still suffer substantial computational costs. As an effective approach for DiT acceleration, feature caching methods are designed to cache the features of DiT in previous timesteps and reuse them in the next timesteps, allowing us to skip the computation in the next timesteps. Among them, token-wise feature caching has been introduced to perform different caching ratios for different tokens in DiTs, aiming to skip the computation for unimportant tokens while still computing the important ones. In this paper, we propose to carefully check the effectiveness in token-wise feature caching with the following two questions: (1) Is it really necessary to compute the so-called "important" tokens in each step? (2) Are so-called important tokens really important? Surprisingly, this paper gives some counterintuition answers, demonstrating that consistently computing the selected "important tokens" in all steps is not necessary. The selection of the so-called "important tokens" is often ineffective, and even sometimes shows inferior performance than random selection. Based on these observations, this paper introduces dual feature caching referred to as DuCa, which performs aggressive caching strategy and conservative caching strategy iteratively and selects the tokens for computing randomly. Extensive experimental results demonstrate the effectiveness of our method in DiT, PixArt, FLUX, and OpenSora, demonstrating significant improvements than the previous token-wise feature caching.
Macrophage activation syndrome (MAS) is driven by a hyperinflammatory response characterized by aberrant activation of lymphocytes and phagocytes. While monocytes and macrophages are thought to be important in MAS pathogenesis, their role remains poorly understood. We used bulk and single-cell RNA sequencing (RNA-Seq) on sorted monocytes from children with MAS and healthy controls to identify transcriptional changes during MAS. We defined a MAS signature in classical monocytes that correlated with ferritin and was elevated in monocytes from systemic lupus erythematosus and COVID-19 patients. We also identified a subset of classical monocytes with high levels of interferon-stimulated genes (ISGs) that expanded during MAS. Surprisingly, the transcriptional signature of these cells was driven by type I IFNs, rather than IFNγ. Consistent with this finding, we detected increased levels of circulating IFNβ during MAS, suggesting that IFNβ plays an unrecognized role in driving MAS monocyte responses. We also identified a MAS-associated CD8 + T cell population with a distinctive transcriptional signature. We used cell-cell communication algorithms to predict increased immunoregulatory interactions between monocytes and T cells during MAS. Together, these results provide new evidence for a role for type I IFN during MAS and identify a unique CD8 + T cell population that may contribute to MAS pathophysiology.
Dopamine has diverse roles in the regulation of reproduction and social behaviors in insects. In the burying beetle, Nicrophorus orbicollis, a species with extended care, our previous work has shown that brain dopamine levels increase significantly after 24 h of care. It is not known, however, whether this increase arises from changes in the expression of genes responsible for dopamine biosynthesis and/or degradation. To that end, we quantified transcript levels of tyrosine hydroxylase (Noth); aromatic amino acid decarboxylase (Noaadc), and dopamine N-acetyltransferase (Nodnat) in head tissue of female burying beetles across four developmental and parental stages: newly-emerged, sexually mature, 1-day parental, and 6-day parental. Surprisingly, transcript levels of Noth, encoding the rate-limiting enzyme, did not increase after 24 h of care relative to non-breeding controls. Moreover, expression of Noaadc, encoding the enzyme involved in the final step of dopamine synthesis, showed a striking, albeit not statistically significant, reduction in actively parenting females at 24 h of care, with transcript levels returning to pre-breeding levels by 6 days of care. In contrast, expression of both Noth and Nodnat was significantly elevated in newly emerged females compared with reproductively mature and parental stages, revealing a pattern of transcriptional upregulation associated with early development, rather than active parenting. The previously observed increase in dopamine during early parenting is thus unlikely to be driven by transcriptional upregulation of biosynthetic genes; post-transcriptional mechanisms, including altered release, turnover, or synaptic signaling, may instead contribute to neuromodulatory changes associated with parental care in burying beetles.
Multimorbidity, the presence of two or more conditions, is associated with a higher risk of death as individuals age. However, modeling multimorbidity in laboratory animals is difficult, if not impossible, because specific conditions are seldom individually diagnosed and treated in these settings. Because of their shared environment, physiology, and genetic diversity, and because they are medically managed as individuals, companion dogs have potential to serve as a translational multimorbidity model. Yet it is unknown how diagnoses accumulate over time, how these diagnoses are associated with mortality, and which multimorbid condition combinations are the most prevalent and hazardous. Utilizing owner-reported data from over 50,000 dogs in the Dog Aging Project (DAP), we assessed how multimorbidities develop, learned which are the most prevalent, and evaluated their impact on survival. Like in humans, we show that the accumulation of conditions is associated with an increased risk of death in dogs. We also present data suggesting that future reported condition rates vary depending on the conditions a dog's owner already has reported. Not surprisingly, our analysis reveals that the overall canine aging process appears to be the driving factor behind disease development, more so than other covariates. Through classifying multimorbidities, we found that almost all either exhibit a synergistic effect or are driven by a single, predominant condition. In both cases, osteoarthritis, overweight, and cancer were highly prevalent throughout. This analysis expands on previously conducted DAP work and further highlights the usefulness of the companion dog as a translational model for human aging.
Honey bee health is adversely affected by numerous biotic and abiotic stressors, such as the extensive use of pesticides, which reduce survival and, even at sublethal doses, impair fitness and behaviour, including learning ability. The proboscis extension reflex (PER) is a widely used method to investigate associative learning in different insect species, such as Apis mellifera ligustica, when exposed to biotic and abiotic stresses. PER protocols require careful insect handling and accurate timing of stimulus application for effective conditioning and precise learning behaviour assessment. Despite the considerable amount of literature on this topic, information on automatising PER protocols for evaluating a large number of insects is limited. In this study, under laboratory conditions we evaluated whether exposure to different lethal concentrations (LC0.2 and LC20) of the natural bioinsecticide spinosad affects olfactory learning in groups of twenty worker bees within the same experimental cycle. For this purpose, we developed and validated an automated, microcontroller-based open-source device designed to standardise key steps of the PER conditioning protocol. Spinosad is a neurotoxic molecule that is known to induce mortality in honey bees, as well as behavioural impairment on locomotion and orientation at low doses. Surprisingly, possible effects on associative learning evaluated through PER are unknown. The sequential steps of the PER protocol were mechanised using a rotating carousel, where the conditioned stimulus was automatically released. The operator manually applied the unconditioned stimulus to the antennae, provided the rewarding solution, and recorded whether each insect exhibited PER behaviour. Bee responses were instantly transmitted to a laptop using a basic serial data transfer protocol and revealed decreased PER response (about 25%) for both spinosad concentrations at 20 min after the last conditioning trial. After small adaptations and validation, we expect that the device can be adopted both in laboratory and field conditions to investigate PER response in other bees, e.g., wild pollinators and bumblebees. This work aligns with current attempts to develop novel tools for monitoring biopesticide effects on pollinator health in changing environments.
Current knowledge of the ovine vaginal microbiota is limited to adult ewes, leaving the bacterial community of nulliparous ewes and its dynamics during their first reproductive handling undefined. This study aimed to characterize the vaginal microbiota of ewe lambs prior to their first breeding and to evaluate the changes caused by routine handling and oestrus synchronization. A total of 66 vaginal samples were collected from 22 nulliparous Latxa ewe lambs at three time points: baseline, post-handling, and post-oestrus synchronization using intravaginal devices containing oxytetracycline. Bacterial composition was characterized by sequencing the V3-V4 hypervariable regions of the 16S rRNA gene. Data were processed using DADA2 to infer Amplicon Sequence Variants, and ecological shifts were evaluated through beta and alpha diversity metrics, alongside differential abundance analysis with ANCOM-BC2. A baseline community was revealed, with high diversity and inter-individual variability. This initial state was dominated by the phylum Firmicutes and showed a strong connection to the gut microbiota, including enteric genera such as Fibrobacter, Rikenellaceae RC9 gut group, and Lachnospiraceae NK3A20 group. The first physical examination caused a significant shift in community structure (beta diversity p = 0.001), marked by a rapid drop in these gut-associated bacteria and an increase in opportunistic genera such as Trueperella (log2FC = 2.18; padj < 0.05). The subsequent synchronization treatment further reduced both alpha and beta diversity, creating a uniform environment where genera such as Aerococcus, Corynebacterium, Finegoldia, and Trueperella increased, while Alistipes, Acinetobacter, and Jeotgalicoccus decreased (Padj < 0.05). Despite these changes, the cohort achieved an 89% pregnancy rate via natural mating. Routine handling and synchronization protocols induce temporary shifts in the vaginal microbiota, decreasing diversity and promoting some opportunistic genera. Crucially, the high fertility rate achieved suggests that these ecological alterations are compatible with successful conception under natural mating conditions. Reproductive management in sheep often involves oestrus synchronization using intravaginal sponges. While the effects on adult ewes are known, the impact on nulliparous ewe lambs remains unclear. This study characterized the vaginal bacteria of 22 Latxa ewe lambs at three stages using 16S rRNA gene amplicon sequencing: baseline, after initial physical handling (hymen rupture), and after sponge removal. At baseline, the ewes hosted diverse bacterial communities, showing similarities to those found in the gut. However, the first physical exam and subsequent hormone treatment significantly altered this environment, reducing bacterial diversity and promoting opportunistic genera often associated with infertility, such as Trueperella. Surprisingly, despite this temporary microbial imbalance, the flock achieved an 89% pregnancy rate. These findings show that while standard reproductive protocols significantly disrupt the vaginal ecosystem of young ewes, the reproductive tract is sufficiently resilient to restore functionality and allow for successful conception via natural mating.
Influenza A virus (IAV) depends on host proteins to complete several important functions, including trafficking viral proteins throughout the cell. Previous work has established a critical role for the cellular vesicular trafficking protein, Rab11A, in transporting the viral genome segments to the site of budding at the plasma membrane. While the role of Rab11A in IAV assembly is relatively well understood, very little is known about the function of a closely related isoform (Rab11B) during influenza virus infection. We have shown that both Rab11A and Rab11B are required for successful IAV infection by current H1N1 or H3N2 isolates. Cells in which either Rab11A or Rab11B were depleted failed to efficiently produce virus, with significant reductions in infectious titer. Surprisingly, our data revealed that recent (2022) H3N2, but not H1N1, isolates failed to efficiently produce viral proteins in single-cycle infections when Rab11B (but not Rab11A) was depleted. Flow cytometry analysis suggests that the defect in protein production is driven by a reduction in the total number of infected cells, rather than a decrease in viral protein production at the single-cell level. Using reverse genetics and "7+1" reassortant viruses, we mapped this Rab11B-dependent early defect in recent H3N2 isolates to the HA gene. RT-qPCR analysis of H3N2 virions bound to the cell surface showed a ~50% decrease in virus binding to the surface of cells depleted of Rab11B, but not Rab11A. Analysis of cell surface α2,6 and α2,3 sialic acids revealed no significant global change in sialic acid profile upon the depletion of Rab11B. As H3N2 virions could be removed by exogenous neuraminidase, the totality of these data suggests that the H3N2 failure to bind is the result of a loss of one (or more) specific sialylated cell surface protein(s) upon Rab11B depletion, rather than a decrease in bulk α2,6 sialic acid levels. These data suggest a novel role for Rab11B during viral entry that is specific to H3N2 isolates.IMPORTANCEInfluenza A is a major human pathogen, which poses risks through both the continuous circulation of "seasonal" influenza viruses (H1N1 and H3N2 subtypes) as well as the emergence of novel pandemic strains from animal hosts. Here, we demonstrate that contemporaneous H3N2 (but not H1N1) subtypes enter human lung cells through a Rab11B-dependent mechanism. This is distinct from the well-known role of Rab11A later in the life cycle, where it mediates the transport of viral ribonucleoprotein complexes to the site of virion assembly. These findings are relevant for assessing the risk that recently emerged zoonotic influenza viruses can enter human lung cells. Our work suggests that H1N1 and H3N2 viruses enter via different routes, which are not dependent on sialic acid levels. Our data provide important foundational information for the growing number of Rab11-dependent viruses, as it suggests that the Rab11 isoforms can affect both viral entry and viral exit.
Animal tissues have diverse architectures and cell behaviors across the epithelial-mesenchymal spectrum. Cell adhesion mediated by classical cadherins is foundational. Cadherins nucleate complexes of dozens of proteins connecting junctions to the cytoskeleton and signaling downstream. Many junctional proteins are well-studied in epithelia, but less is known about roles during mesenchymal migration. The nascent myotubes of the pupal Drosophila testis provide an excellent model for N-cadherin mediated mesenchymal migration. We combined a proximity proteomics dataset of adherens junction proteins in mammalian epithelial cells with genome-wide shRNA libraries knocking down Drosophila genes to begin to define the subset of junctional proteins important in mesenchymal migration. While N-cadherin is predominant, E-cadherin plays a supporting role. Surprisingly, several proteins with key roles in epithelial morphogenesis, including Afadin's homolog Canoe, ZO-1's homolog Polychaetoid, and Par3's homolog Bazooka play at most modest roles. Twenty-two genes with diverse cell biological roles had strong to moderate defects in testis morphogenesis. These will provide a community resource. We followed up two. The kinase Par-1 is important for migration and gap closure, with knockdown phenotypes paralleling those of myosin. The Rab GAP RN-tre does not have roles until after migration and works in parallel with N-cadherin during testis spiralization.
In 2020, a new swine influenza H1avN2#E genotype emerged in pig farms in France. Shortly after its emergence in swine, this virus was detected in breeding turkey farms, and was responsible of a zoonotic infection. Phylogenetic analyses previously conducted on viral sequences led to the selection of three viruses: the first strain detected in turkeys, resulting from a recent spillover from swine to turkeys (A); a second virus also detected in turkeys and likely adapted to this species (B); and a swine reference strain (C). In the context of species-barrier crossing, the aim of this study was to characterize in vivo these three viruses in an avian model, the breeding turkey, and in a mammalian model, the mouse. Clinical signs, lesions, viral loads, and immune responses were evaluated. In turkeys inoculated experimentally, all three viruses caused similar very mild clinical signs and no viral shedding. In contrast, in mice, virus A caused marked clinical signs associated with mortality, along with a weak inflammatory response. Conversely, virus C caused few clinical signs but showed a more pronounced inflammatory response. Surprisingly, only two nonsynonymous mutations were present between viruses C and A: K189R in PB1 and E233K in HA. Virus B displayed an intermediate profile. There was no difference in genomic load in the lungs among the three viruses, suggesting that the observed differences in pathogenicity were due to the immune response rather than viral replication.
The use of two grating monochromators in fluorescence detectors coupled to chromatographic systems has been associated with some unexplained optical effects and anomalous results in the literature. The recently introduced zero-order excitation/emission mode, in which the corresponding grating directs the entire lamp spectrum to the flow cell or the emission spectrum to the photomultiplier tube, introduces additional complexities. The consequences of these optical properties in HPLC-FLDs are investigated. For the tested UV emitters, sensitivity surprisingly dropped up to 10-fold under zero-order diffraction, whereas for the visible fluorophores, sensitivity increased up to 3.6-fold in a nonlinear fashion, depending on the analyte's emission spectrum. This effect is not from a "sag" in photomultiplier gain from scattered light; the rapid increase or decrease in HPLC-FLD signal is caused by (often undisclosed) blazing of holographic diffraction gratings. An optical test based on Rayleigh scattering is developed that predicts the wavelengths at which zero-order diffraction is advantageous versus where it degrades the signal. A one-plus log transform of emission scans revealed a continuous, buried background of higher-order diffraction contributions from monochromators. A robust z-transform tool has been developed in MATLAB®, enabling analysts to view impurities in emission heat maps that would otherwise be invisible. The proposed optical test for assessing the zero-order advantage applies to all HPLC-FLDs under isocratic or gradient conditions. Zero-order diffraction detection can lower the detection limit for visible-light emitters if the grating is blazed for the UV region. Understanding these optical effects enables more reliable ultra-trace fluorescence detection.
GFAP is a type III intermediate filament primarily found within astrocytes and is known to maintain proper cell structure and mechanical strength. Mutations in GFAP are implicated in the pathology of Alexander disease, a neurodegenerative disease characterized by cytoplasmic inclusions of protein, known as Rosenthal fibers. GFAP has a typical type III intermediate filament domain structure, consisting of a highly conserved alpha-helical rod domain bracketed by an intrinsically disordered N-terminal head and C-terminal tail domains. While the general domain organization of monomeric GFAP and the assembly process for higher order quaternary structures are known, we lack an atomic resolution mechanistic understanding of GFAP assembly into mature filaments. Understanding the structure of GFAP filaments and how mutations disrupt this structure will provide vital information into how mutations produce Alexander disease pathology. As a first step towards a mechanistic description, we characterized GFAP wild type tetrameric and filamentous assemblies using solid state NMR and compared the results to those obtained from an assembly-deficient GFAP mutant. For wild-type GFAP, we observe surprisingly uniform rigid alpha helical structure and can spectroscopically resolve highly mobile intrinsically disordered regions in the filament assemblies. Wild type tetramers show increased mobility, likely arising from the head and tail domains. Mutation of the highly conserved cysteine at position 294 to serine results in an inability to form full-length filament assemblies. We show that the rigid regions of the C294S mutant assemblies largely remain structurally consistent with wild type tetrameric assemblies but differ from wild-type filament assemblies. There is an increase in highly mobile regions for the C294S mutant relative to the wild-type. Our results provide a foundation for developing solid state NMR approaches to characterize intermediate filament assembly mechanisms and the interfering effect of disease mutations.
We installed molecular CO2 reduction (CO2R) catalysts directly onto Si (photo)electrodes. The highly reactive M(5-azido-1,10-phenanthroline)(CO)3X (where M = Mn or Re, X = Br or Cl) complexes readily bubbled when dissolved in polar organic solvents, in both the presence and absence of an ultraviolet light source. When placed on hydrogen-terminated Si (H-Si) and native silicon oxide (SiOx), similar amounts of the complex were attached to the surface under illumination (367 nm, 50-200 mW/cm2) or in the dark. Surprisingly, these films revealed submonolayer coverages instead of the multilayered structures we expected. DFT analyses support monolayer formation, showing that the triplet-state nitrene of the complex is more energetically favorable than the singlet state. Using controlled-potential electrolysis experiments, we showed that Re- and Mn-containing films on pSi photoelectrodes generated small amounts of CO when exposed to 1 atm of CO2 and 1 sun illumination. These amounts of CO were an order of magnitude greater than control surfaces, producing 5.59 × 10-7 mol CO/h for Re(az-phen) and 7.83 × 10-7 mol CO/h for Mn(az-phen) films. Much of the charge passed at the pSi electrodes was consumed by the competing hydrogen evolution reaction, which we attribute to the low molecular coverage and the presence of native oxide on the electrode surface after attachment. This work demonstrates the feasibility of reacting azide-containing ligands with Si surfaces. Still, it highlights the need for alternative ligand structures and reaction conditions to form multilayer films.
Growth-regulated oncogene‑α (GRO‑α) has been widely reported in tumorigenesis. However, the specific contribution of GRO‑α to the malignant behaviors of triple-negative breast cancer (TNBC) remains unclear. Bioinformatics analyses were conducted using the UALCAN and TIMER databases. The underlying mechanism of action of GRO‑α on the progression of TNBC MDA-MB-231 cells was investigated using CCK‑8, EdU, transwell and Western blotting assays. TNBC tissues exhibited elevated expression of GRO‑α, and its high expression was positively correlated with tumor immune cytokines and immune cell recruitment. The growth and migration of TNBC MDA-MB-231 cells were significantly enhanced following treatment with recombinant GRO‑α. Consistently, the protein levels of AKT, p‑mTOR, and mTOR in MDA-MB-231 cells were extremely elevated by recombinant GRO‑α. In addition, the malignant behaviors induced by GRO‑α were surprisingly attenuated following treatment with mTOR inhibitor Torin1. GRO‑α may play a role in the malignant progression of TNBC in an AKT-mTOR-dependent manner.
Despite extensive study, how conscious and unconscious priming influence visual perception remains only partially understood. In this work, we examine their distinct effects across multiple experimental conditions within a binocular rivalry paradigm to provide a more comprehensive perspective on identity and category recognition. Participants were presented with word or image primes, followed by a name-picture verification task in which faces or animal bodies served as targets. Although conscious priming has been shown to facilitate identity recognition while interfering with category perception, the precise distinction between conscious and unconscious states, as well as the mechanisms underlying unconscious priming, requires further detailed analysis. Left-hemispheric processing was one of the influential factors in distinguishing conscious from unconscious priming effects. Interestingly, we observed a negative correlation between conscious and unconscious perception during identity recognition, highlighting the condition-dependent modulation of visual perception in the priming paradigm. From the regression analyses, awareness showed the strongest predictor of priming magnitude, with recognition level playing a secondary role. More broadly, our findings demonstrate that visual perception circuits are modulated condition-dependently, underscoring how awareness and trial context jointly shape recognition processes. Conscious priming facilitated identity but impaired category recognition.Unconscious priming lacked identity-category dissociation.Identity priming showed negative conscious-unconscious correlation.Right visual field effects distinguished awareness states.Awareness was the strongest predictor of priming magnitude. Our brains are constantly influenced by things we have just seen-even when we are not aware of seeing them. This phenomenon is called priming. In this study, we explored how visible (conscious) and invisible (unconscious) hints affect the way people recognize images. Participants viewed brief words or pictures before being asked to identify either a specific individual (for example, a particular dog breed or person) or a broader category (such as "dog" or "animal"). Sometimes these hints were clearly visible. Other times they were hidden from awareness using a special visual technique. We found that when people were consciously aware of the hint, it helped them recognize specific identities faster-but surprisingly, it made them slower at recognizing broader categories. In contrast, when the hint was invisible, this clear pattern disappeared. Even more interesting, for identity recognition, the effects of visible and invisible hints often moved in opposite directions. What helped in the conscious condition could hinder in the unconscious one. We also discovered that awareness itself was the most important factor shaping these effects- more important than whether the hint was a word or picture, or whether it appeared on the left or right side of the screen. Why does this matter? These findings show that conscious and unconscious influences on perception are not simply weaker or stronger versions of the same process-they work differently. Understanding how awareness shapes recognition may help us better understand attention, decision-making, advertising effects, and even clinical conditions where perception or awareness is altered.
The gene expression changes associated with memory acquisition, consolidation and reconsolidation-all active epochs in memory formation-have been well characterized in the rodent hippocampus. Less is known, however, of the changes in gene expression during the offline maintenance of memory. In this study, we measured the gene expression changes in the dorsal hippocampus of four mice 3 days after consolidation of an active place avoidance memory. We examined gene expression changes in a putative subset of memory-associated neurons by leveraging the immediate early gene in vivo tagging system of the Arc-Cre/flox-eYFP transgenic mouse line. Through spatial transcriptomics we found that memory trained animals exhibited spatially regionalized expression of genes involved in post-synaptic function in CA1, synaptic vesicle transport in CA3, and neuronal differentiation in DG. Surprisingly, these gene expression enrichments were not observed in eYFP mRNA positive spatial spots. To gain granularity into this finding, we carried out single nuclear RNA sequencing, which confirmed enrichment of differentially expressed genes associated with synaptic plasticity and post-synaptic signaling unique to each subregion in trained animals, but not from their eYFP mRNA positive nuclei. Notably, nuclei of hippocampal neurons were largely characterized by their down regulation of genes involved in ATP synthesis and cytoplasmic translation. Our results suggest that two overarching transcriptomic patterns contribute to the functional changes in hippocampal cells during offline memory maintenance: regionally distributed expression of genes linked to synaptic functions (with concomitant sparseness of memory-associated neuronal ensembles) and a reduction of metabolic activity related genes across hippocampal sub-regions.