Enhanced protein-metabolite correlation analysis: To investigate the association between Staphylococcus aureus mastitis and metabolic immune pathways.

Mastitis is a disease characterized by congestion, swelling, and inflammation of the mammary gland and usually caused by infection with pathogenic microorganisms. Furthermore, the development of mastitis is closely linked to the exogenous pathway of the gastrointestinal tract. However, the regulatory mechanisms governing the gut-metabolism-mammary axis remain incompletely understood. The present study revealed alterations in the gut microbiota of mastitis rats characterized by an increased abundance of the Proteobacteria phylum. Plasma analysis revealed significantly higher levels of L-isoleucine and cholic acid along with 7-ketodeoxycholic acid. Mammary tissue showed elevated levels of arachidonic acid metabolites and norlithocholic acid. Proteomic analysis showed increased levels of IFIH1, Tnfaip8l2, IRGM, and IRF5 in mastitis rats, which suggests that mastitis triggers an inflammatory response and immune stress. Follistatin (Fst) and progesterone receptor (Pgr) were significantly downregulated, raising the risk of breast cancer. Extracellular matrix (ECM) receptors and focal adhesion signaling pathways were downregulated, while blood-milk barrier integrity was disrupted. Analysis of protein-metabolic network regulation revealed that necroptosis, protein digestion and absorption, and arachidonic acid metabolism were the principal regulatory pathways involved in the development of mastitis. In short, the onset of mastitis leads to changes in the microbiota and alterations in the metabolic profiles of various biological samples, including colonic contents, plasma, and mammary tissue. Key manifestations include disturbances in bile acid metabolism, amino acid metabolism, and arachidonic acid metabolism. At the same time, the integrity of the blood-milk barrier is compromised while inflammation is promoted, thereby reducing cell adhesion in the mammary glands. These findings contribute to a more comprehensive understanding of the metabolic status of mastitis and provide new insights into its impact on the immune system.

Evaluation standards regulate the generation and selection of novel ideas in creative behaviors: insights from individual differences in event-related potentials.

Evaluation is generally considered to occur after the generation of novel ideas to select truly creative ideas; however, evaluation may occur concurrently with the generation and regulate its efficiency. To test this hypothesis, 120 participants who held strict, moderate, or loose evaluation standards were grouped, and neural responses related to novel idea generation were compared retrospectively. The results showed that lower N400 amplitudes and greater LSP amplitudes were simultaneously elicited by objectively defined novel and usable options than by novel but unusable options among participants with moderate standards but not among participants with strict or loose standards. Evaluation standards influence the efficiency of novel idea generation; neither strict nor loose evaluation standards are conducive to fully resolving cognitive conflicts and generating novel ideas. Moreover, lower N400 amplitudes and greater LSP amplitudes were simultaneously elicited by the subjectively rated novel and usable option than by the novel but unusable option among participants with strict and moderate standards but not among participants with loose standards. Evaluation standards influence the selection among the generated ideas; participants in the strict and moderate groups made a wise choice based on the degree of conflict resolution, whereas participants in the loose group did not.

Memory enhancement for emotional words is attributed to both valence and arousal.

We do not memorize items in our surroundings with equal priority. Previous literature has widely shown that emotional stimuli are better remembered than neutral stimuli. However, given emotional stimuli and neutral stimuli often differ in both valence and arousal dimensions, it remains unclear whether the enhancement effects can be attributed to valence, or just to arousal. Importantly, most prior studies relied on a relatively small number of stimuli and non-emotional factors such as word length, imageability and other confounds were hard to control. To address these challenges, we analyzed multiple large databases of recognition memory and free recall tasks from previous research by items with many lexical and semantic covariates included, examining the effects of valence or arousal when controlling for each other. Our results showed a U-shaped relationship between valence and memory performance for both recognition and free recall, and a linear relationship between arousal and memory performance for both tasks. These findings showed that the memory enhancement effects can be attributed to both valence and arousal. We demonstrated these effects with generalizability across many stimuli and controlled for non-emotional factors. Together, these findings disentangle the contribution of valence and arousal in emotional memory enhancement effects and provide insights for current major theories of emotional memory.

Promoting the healing of diabetic wounds with an antimicrobial gel containing AgNPs with anti-infective and anti-inflammatory properties.

Diabetic wounds are prone to develop chronic wounds due to bacterial infection and persistent inflammatory response. However, traditional dressings are monofunctional, lack bioactive substances, have limited bacterial inhibition as well as difficulties in adhesion and retention. These limit the therapeutic efficacy of traditional dressings on diabetic wounds. Therefore, finding and developing efficient and safe wound dressings is currently an urgent clinical need. In this study, an antimicrobial gel loaded with silver nanoparticles (AgNPs) (referred to as AgNPs@QAC-CBM) was prepared by crosslinking quaternary ammonium chitosan (QAC) with carbomer (CBM) as a gel matrix. AgNPs@QAC-CBM exhibited a reticulated structure, strong adhesion, good stability, and remarkable bactericidal properties, killing 99.9% of Escherichia coli, Staphylococcus aureus, Candida albicans, and Pseudomonas aeruginosa within 1 min. Furthermore, AgNPs@QAC-CBM improved the wound microenvironment and accelerated wound healing in diabetic mice by promoting tissue production and collagen deposition, inducing M2 macrophages, reducing pro-inflammatory factor secretion and increasing anti-inflammatory factor levels. Moreover, AgNPs@QAC-CBM was proven to be safe for use through skin irritation and cytotoxicity tests, as they did not cause any irritation or toxicity. To summarize, AgNPs@QAC-CBM showed promising potential in enhancing the diabetic wound healing process.

Structural analysis of polysaccharide from Inonotus obliquus and investigate combined impact on the sex hormones, intestinal microbiota and metabolism in SPF male mice.

The dysregulation of sex hormone levels is associated with metabolic disorders such as obesity. Inonotus obliquus polysaccharide (IOP) exhibits a promising therapeutic effect on conditions like obesity and diabetes, potentially linked to its influence on intestinal microbiota and metabolism. The exact cause and mechanisms that link sex hormones, gut microbiota and metabolism are still unknown. In this research, we examined the molecular weight, monosaccharide composition, and glycosidic bond type of IOP. We found that IOP mostly consists of alpha-structured 6­carbon glucopyranose, with a predominant (1 â†’ 4) linkage to monosaccharides and a uniform distribution. Following this, we administered two different concentrations of IOP to mice through gavage. The results of the enzyme-linked immunosorbent assay (ELISA) demonstrated a significant increase in testosterone (T) levels in the IOP group as compared to the control group. Additionally, the results of tissue immunofluorescence indicated that increased IOP led to a decrease in adiponectin content and an increase in SET protein expression. The study also revealed changes in the intestinal microbiota and metabolic changes in mice through 16S rRNA data and non-targeted LC-MS data, respectively. The study also found that IOP mainly affects pathways linked to glycerophospholipid metabolism. In addition, it has been observed that there is an increase in the number of beneficial bacteria, such as the Eubacterium coprostanoligenes group and g.Lachnospiraceae NK4A136 group, while the levels of metabolites that are linked to obesity or diabetes, such as 1,5-anhydrosorbitol, are reduced. Furthermore, biomarker screening has revealed that the main microorganism responsible for the differences between the three groups is g.Erysipelatoclostridiaceae. In summary, these findings suggest that IOP exerts its therapeutic effects through a synergistic interplay between sex hormones, gut microbiome composition, and metabolic processes.

Divergent thinking benefits from functional antagonism of the left IFG and right TPJ: a transcranial direct current stimulation study.

Divergent thinking is assumed to benefit from releasing the constraint of existing knowledge (i.e. top-down control) and enriching free association (i.e. bottom-up processing). However, whether functional antagonism between top-down control-related and bottom-up processing-related brain structures is conducive to generating original ideas is largely unknown. This study was designed to investigate the effect of functional antagonism between the left inferior frontal gyrus and the right temporoparietal junction on divergent thinking performance. A within-subjects design was adopted for three experiments. A total of 114 participants performed divergent thinking tasks after receiving transcranial direct current stimulation over target regions. In particular, cathodal stimulation over the left inferior frontal gyrus and anodal stimulation over the right inferior frontal gyrus (Experiment 1), anodal stimulation over the right temporoparietal junction (Experiment 2), and both cathodal stimulation over the left inferior frontal gyrus and anodal stimulation over the right temporoparietal junction (Experiment 3) were manipulated. Compared with sham stimulation, the combination of hyperpolarization of the left inferior frontal gyrus and depolarization of the right temporoparietal junction comprehensively promoted the fluency, flexibility, and originality of divergent thinking without decreasing the rationality of generated ideas. Functional antagonism between the left inferior frontal gyrus (hyperpolarization) and right temporoparietal junction (depolarization) has a "1 + 1 > 2" superposition effect on divergent thinking.

IGF2BP3 Regulates TMA7-mediated Autophagy and Cisplatin Resistance in Laryngeal Cancer via m6A RNA Methylation.

Translation machinery associated 7 homolog (TMA7) is closely related to proliferation-related diseases. However, the function and regulatory mechanism of TMA7 in laryngeal squamous cell carcinoma (LSCC) remain unclear. The present study aimed to investigate the effect of TMA7 on the occurrence and development of LSCC and to study the mechanism of TMA7. TMA7 is upregulated in LSCC tissues and associated with poor prognosis. After TMA7 downregulation, the autophagy level was increased, and the proliferation, migration, and invasion of LSCC cells were inhibited. The m6A methylated reader IGF2BP3 enhanced the stability of TMA7 and reduced the level of autophagy. TMA7 interacted directly with UBA2. Furthermore, the activation of the IGF2BP3-regulated TMA7-UBA2-PI3K pathway is the primary mechanism by which TMA7 inhibits autophagy and promotes the progression of LSCC. The current study revealed that IGF2BP3-mediated TMA7 m6A modification promotes LSCC progression and cisplatin-resistance through UBA2-PI3K pathway, providing new insights into the autophagy-related mechanism, potential biomarkers, and therapeutic targets for LSCC.

Cognitive control in creative discovery: The gap between ideal and reality.

Creative discovery involves discovering the additional values of existing things in the environment by identifying the novel associations between seemingly unrelated things; the judgment made in this process is expected to be accurate but not entirely correct. From the perspective of cognitive processing, what is the difference between the ideal and real states of creative discovery? This is largely unknown. In this study, a daily life scenario was presented, and a great number of seemingly unrelated tools were presented for participants to discover valuable tools. Electrophysiological activity was recorded when participants identified tools, and we then retrospectively analyzed the differences between responses. Compared with usual tools, unusual tools evoked greater N2, N400 and late sustained potential (LSP) amplitudes, which was likely associated with the monitoring and resolution of cognitive conflicts. Moreover, unusual tools evoked smaller N400 and greater LSP amplitudes when correctly identified as usable than when identified as unusable; this result suggested that creative discovery in the ideal state should depend on the cognitive control involved in resolving conflicts. However, in the comparison between subjectively rated usable and unusable tools, smaller N400 and greater LSP amplitudes were observed only when unusual tools could be identified by expanding the application scope but not by releasing functional fixedness; this outcome suggested that creative discovery in the real state was not always influenced by the cognitive control involved in resolving conflicts. The difference in cognitive control that should be exerted and that was actually exerted to identify novel associations was discussed.

When and why will creative discovery succeed or fail? The role of reactive control in resolving conflicts.

The process of creative discovery refers to discovering additional values of existing objects by identifying novel associations between seemingly unrelated things; however, this process is not always successful. To reveal the dynamic process of creative discovery, particularly when and why people made right or wrong judgments, the daily life scenario was described, and a possible tool was presented for judging whether it is usable to solve problems. Electrophysiological activity was recorded when people identified novel tools and then retrospectively analyzed the differences among three responses: correctly identified novel and usable (C-NU) options, falsely identified novel and usable (F-NU) options, and correctly identified novel but unusable (C-NUU) options. The results showed that, compared with ordinary tools, novel tools evoked greater N2, N400 and LSP amplitudes; the differences in these components were likely associated with the monitoring and resolution of cognitive conflicts in the process of discovering novel associations. Regarding novel tools, smaller N400 and greater LSP amplitudes were evoked by the C-NU option than by the F-NU option, and no differences in these components were found between the F-NU and C-NUU options. The findings revealed that the success or failure of discovering novel associations depended on reactive control in resolving conflicts. Only when sufficient cognitive effort is used to resolve a conflict to a great degree can the appropriately novel association be successfully discovered; otherwise, the novel and appropriate association is lost.

Functional lateralization of the medial temporal lobe in novel associative processing during creativity evaluation.

Although hemispheric lateralization of creativity has been a longstanding topic of debate, the underlying neurocognitive mechanism remains poorly understood. Here we designed 2 types of novel stimuli-"novel useful and novel useless," adapted from "familiar useful" designs taken from daily life-to demonstrate how the left and right medial temporal lobe (MTL) respond to novel designs of different usefulness. Taking the "familiar useful" design as a baseline, we found that the right MTL showed increased activation in response to "novel useful" designs, followed by "novel useless" ones, while the left MTL only showed increased activation in response to "novel useful" designs. Calculating an asymmetry index suggests that usefulness processing is predominant in the left MTL, whereas the right MTL is predominantly involved in novelty processing. Moreover, the left parahippocampal gyrus (PHG) showed stronger functional connectivity with the anterior cingulate cortex when responding to "novel useless" designs. In contrast, the right PHG showed stronger connectivity with the amygdala, midbrain, and hippocampus. Critically, multivoxel representational similarity analyses revealed that the left MTL was more effective than the right MTL at distinguishing the usefulness differences in novel stimuli, while representational patterns in the left PHG positively predicted the post-behavior evaluation of "truly creative" products. These findings suggest an apparent dissociation of the left and right MTL in integrating the novelty and usefulness information and novel associative processing during creativity evaluation, respectively. Our results provide novel insights into a longstanding and controversial question in creativity research by demonstrating functional lateralization of the MTL in processing novel associations.

Emotional learning retroactively promotes memory integration through rapid neural reactivation and reorganization.

Neutral events preceding emotional experiences can be better remembered, likely by assigning them as significant to guide possible use in future. Yet, the neurobiological mechanisms of how emotional learning enhances memory for past mundane events remain unclear. By two behavioral studies and one functional magnetic resonance imaging study with an adapted sensory preconditioning paradigm, we show rapid neural reactivation and connectivity changes underlying emotion-charged retroactive memory enhancement. Behaviorally, emotional learning retroactively enhanced initial memory for neutral associations across the three studies. Neurally, emotional learning potentiated trial-specific reactivation of overlapping neural traces in the hippocampus and stimulus-relevant neocortex. It further induced rapid hippocampal-neocortical functional reorganization supporting such retroactive memory benefit, as characterized by enhanced hippocampal-neocortical coupling modulated by the amygdala during emotional learning, and a shift of hippocampal connectivity from stimulus-relevant neocortex to distributed transmodal prefrontal-parietal areas at post-learning rests. Together, emotional learning retroactively promotes memory integration for past neutral events through stimulating trial-specific reactivation of overlapping representations and reorganization of associated memories into an integrated network to foster its priority for future use.

Cognitive control of invalid predominant ideas in insight-like problem solving.

Predominant ordinary ideas are insufficient for solving insight-like problems; they interfere with subordinate original ideas and can produce a mental impasse. However, how people monitor and control invalid predominant ideas remains largely unknown. In the current study, participants were asked to solve a sequence of several similar practice problems that had the same solution to strengthen a predominant idea; the participants were then presented with an insight-like test problem that could not be solved by the predominant idea. The results showed that if the test problem was similar to the practice problems in which the predominant idea could typically be applied, it elicited greater late sustained potential (LSP) over the whole brain but no conflict-related N2 or N400 components, which suggests that the participants did not experience cognitive conflict and continued to verify the predominant but currently invalid idea. When the test problem differed from the practice problems, the items that participants reported trying to solve elicited greater N2-N400 and LSP over the whole brain, which suggests that the participants experienced cognitive conflict and exerted more reactive control over the invalid predominant idea; in contrast, the items that participants reported thinking about how to solve did not evoke greater conflict-related N2-N400 components and evoked even lower LSP, which likely indicates an ineffective state. These findings demonstrate three kinds of cognitive control toward invalid predominant ideas in situations where they are typically and not typically applied and provide empirical evidence of a mental impasse in insight-like problem-solving behaviors.

Expectations Attenuate the Negative Influence of Neural Adaptation on the Processing of Novel Stimuli: ERP Evidence.

When processing repeated stimuli, the neural response is attenuated (i.e., neural adaptation) and performance seems to be facilitated; however, this neural adaptation negatively influences the subsequent processing of novel stimuli. The present study was designed to test whether and how temporal expectations reduce neural adaptation and attenuate the negative influence of neural adaptation on subsequent novel problem solving. Temporal expectations were experimentally manipulated by asking participants to solve a novel problem following three to five repeated problems, generating the expectation of repeated events in the first three serial positions as well as that of novel events in the fourth to sixth serial positions. Compared to the first occurrence, repeated problems evoked more negative deflections, including greater N1, lower P2 and greater LNC amplitudes, regardless of whether participants expected a repeated or novel event; however, the mean amplitudes of the P2 and LNC were smaller in the latter condition. These results show neural adaptation during processing of repeated stimuli and demonstrate that neural adaptation is reduced when a novel event is expected. Regarding the novel events, the conflict monitoring- and resolution-related N400, P600 and LNC amplitudes decreased with decreased neural adaptation. These results indicate that the expectation of novel events attenuate the negative influence of neural adaptation on the subsequent processing of novel events. This study provides new insight into alleviating the constraints imposed by frequently used knowledge on the processing of novel stimuli.

Reactive control in evaluating appropriately or inappropriately novel ideas: Evidence from electrophysiological measures.

Novelty and appropriateness have been considered two necessary criteria to distinguish creative ideas, but little is known about what kind of reactive control people will make when they evaluate appropriately or inappropriately novel ideas. To study this issue, high-density technology was used to record electroencephalography (EEG) signals when participants were evaluating ideas in novel & appropriate, novel & inappropriate, ordinary & appropriate, and ordinary & inappropriate conditions. An analysis of event-related potentials (ERPs) revealed that greater conflict detection-related N2 and N400-like components over the anterior scalp appeared in novel conditions than in ordinary conditions, suggesting that people are able to rapidly monitor novel ideas. Afterward, the mean amplitudes of the LPC over the left anterior scalp were greater in novel & appropriate condition than ordinary & appropriate condition, but no difference was found between novel & appropriate and novel & inappropriate conditions, which likely displayed much more reactive control was recruited to handle novel ideas and no additional control was recruited when the novel ideas were inappropriate. In addition, the mean amplitudes of the LPC/LNC over the posterior scalp were greater in novel than ordinary conditions and were also greater in inappropriate than appropriate conditions, which likely reflected the processing difficulties of conceptual understanding. These findings revealed the early rise monitoring, conceptual understanding, and reactive control mechanism underlying the evaluation of novel ideas.

Glycan Biosynthesis Ability of Gut Microbiota Increased in Primary Hypertension Patients Taking Antihypertension Medications and Potentially Promoted by Macrophage-Adenosine Monophosphate-Activated Protein Kinase.

Increasing evidences suggest that the gut microbiota have their contributions to the hypertension, but the metagenomic characteristics and potential regulating mechanisms in primary hypertension patients taking antihypertension drugs are not clear yet. We carried out a metagenomic analysis in 30 primary hypertension patients taking antihypertension medications and eight healthy adults without any medication. We found that bacterial strains from species, such as Bacteroides fragilis, Bacteroides vulgatus, Escherichia coli, Klebsiella pneumoniae, and Streptococcus vestibularis, were highly increased in patients; and these strains were reported to generate glycan, short-chain fatty acid (SCFA) and trimethylamine (TMA) or be opportunistic pathogens. Meanwhile, Dorea longicatena, Eubacterium hallii, Clostridium leptum, Faecalibacterium prausnitzii, and some other strains were greatly decreased in the patient group. The Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis found that ortholog groups and pathways related to glycan biosynthesis and multidrug resistance were significantly increased in the patient group, and some of the hub genes related to N-glycan biosynthesis were increased in the patient group, while those related to TMA precursor metabolism and amino acid metabolism both increased and decreased in the patient group. Metabolites tested by untargeted liquid chromatography-mass spectrometry (LC-MS) proved the decrease of acetic acid, choline, betaine, and several amino acids in patients' fecal samples. Moreover, meta-analysis of recent studies found that almost all patients were taking at least one kind of drugs that were reported to regulate adenosine monophosphate-activated protein kinase (AMPK) pathway, so we further investigated if AMPK regulated the metagenomic changes by using angiotensin II-induced mouse hypertensive model on wild-type and macrophage-specific AMPK-knockout mice. We found that the changes in E. coli and Dorea and glycan biosynthesis-related orthologs and pathways were similar in our cohort and hypertensive wild-type mice but reversed after AMPK knockout. These results suggest that the gut microbiota-derived glycan, SCFA, TMA, and some other metabolites change in medication-taking primary hypertension patients and that medications might promote gut microbiota glycan biosynthesis through activating macrophage-AMPK.

The dynamic monitoring and control mechanism in problem solving: Evidence from theta and alpha oscillations.

Although both originality and value are considered necessary criteria to identify creative ideas, little is known about how original and valuable ideas are generated in the human brain. To reveal how people monitor and control ongoing processing in the pursuit of original and valuable ideas, high-density electroencephalography (EEG) was used to record electrophysiological signals when participants were performing chunk decomposition tasks via novel-appropriate, novel-inappropriate, ordinary-appropriate and ordinary-inappropriate pathways. The results showed that approximately 100 ms after the problem was presented, novel pathways showed increased theta synchronization in the frontal sites compared to ordinary pathways. Novel pathways were associated with increased alpha desynchronization over the entire brain scale. These theta and alpha oscillations likely indicated rapid monitoring and effective control of novel processing in thinking. In the latter stages of problem solving, particularly during the 2000-2600-ms intervals, increased theta synchronization with decreased alpha desynchronization was found between novel-inappropriate and novel-appropriate pathways, which likely indicated slow monitoring and less control of inappropriate processing in novel thinking. The findings demonstrated the dynamic monitoring and control mechanism in the pursuit of original and valuable ideas.

In search of the emotional experience of innovative products across categories.

Although the innovative designs deliver, superior customer value has long been noted. However, the emotional experience of innovative products brings remains mostly unknown. This work focuses on two kinds of innovative products: function innovation (FI) and design innovation (DI), to uncover the mystery of the emotional experience, these two types of innovative designs bring. Participants in Study 1 were required to subjectively report their practical, emotional experience of the two kinds of innovative designs. The result showed that the emotional experience of innovation products might be a mixture of emotionality. Also, FI and DI products may cause different emotional experiences performance. Multidimensional scaling was employed in Study 2 to simplify the dimensions of these reported emotions to investigate the difference of emotion dimensions distribution that FI and DI brings. The results showed that DI products mainly reflected strong arouse than FI in positive emotions. However, DI product brings more negative emotions than positive emotions. Whereas, FI product did not show the quantitative differences between positive and negative emotions. In Study 3, the difference between FI and DI in emotion intensity was investigated, and the result indicates that both FI and DI products can bring high-intensity positive emotion. However, the DI brings higher intensity negative emotion and lower intensity positive emotion than FI. These studies demonstrate the first direct evidence of the essence of the difference between FI and DI emotion experience and suggest possible guidance for consumers to avoid the effect of the emotions when choosing innovative products.