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Objective: Previous studies have found that patients with Major Depressive Disorder (MDD) exhibit impaired visual motion perception capabilities, and multi-level abnormalities in the human middle temporal complex (MT+), a key brain area for processing visual motion information. However, the brain activity pattern of MDD patients during the perception of visual motion information is currently unclear. In order to study the effect of depression on the activity and functional connectivity (FC) of MT+ during the perception of visual motion information, we conducted a study combining task-state fMRI and psychophysical paradigm to compare MDD patients and healthy control (HC). Methods: Duration threshold was examined through a visual motion perception psychophysical experiment. In addition, a classic block-design grating motion task was utilized for fMRI scanning of 24 MDD patients and 25 HC. The grating moved randomly in one of eight directions. We examined the neural activation under visual stimulation conditions compared to the baseline and FC. Results: Compared to HC group, MDD patients exhibited increased duration threshold. During the task, MDD patients showed decreased beta value and percent signal change in left and right MT+. In the sample comprising MDD and HC, there was a significant negative correlation between beta value in right MT+ and duration threshold. And in MDD group, activation in MT+ were significantly correlated with retardation score. Notably, no such differences in activation were observed in primary visual cortex (V1). Furthermore, when left MT+ served as the seed region, compared to the HC, MDD group showed increased FC with right calcarine fissure and surrounding cortex and decreased FC with left precuneus. Conclusion: Overall, the findings of this study highlight that the visual motion perception function impairment in MDD patients relates to abnormal activation patterns in MT+, and task-related activity are significantly connected to the retardation symptoms of the disease. This not only provides insights into the potential neurobiological mechanisms behind visual motion perception disorder in MDD patients from the aspect of task-related brain activity, but also supports the importance of MT+ as a candidate biomarker region for MDD. [ABSTRACT FROM AUTHOR]

Hyporheic exchange flow, the movement of river water into streambed sediments and its subsequent return to the surface water after suffering biogeochemical transformations, impacts a stream's water quality and ecology. These processes, which are the basis for the self-purification capacity of river systems, depend on the quantity and travel time of the flow within the sediments. Different tracer-based approaches have been deployed for studying flow in saturated sediments, but few of these experimental methodologies are able to attain the high temporal resolutions that are needed to adequately capture the passage of a solute plume in a porous medium. To allow for a better description of such flows, we designed and fabricated an innovative, low-cost sensor system able to detect solute transport at multiple locations simultaneously at very high time resolutions. The sensors measure electrical conductivity as voltage drops at a frequency of up to 10 Hz, allowing for detailed solute breakthrough curves (BTCs). The fabricated sensors were tested in a laboratory experimental setup designed to examine solute transport under conditions that reproduce 1D flow in saturated sediments. The sensor system was able to successfully detect electrical conductivity (expressed as voltage drop) in real-time, at high temporal resolution, and at multiple locations. Solute BTCs collected with the system were consistent and highly repeatable under the same conditions. One-dimensional solute transport equations were modeled numerically using the finite differences technique, and the results showed good agreement between the measured and modeled BTCs for all materials. The proposed system is inexpensive compared to conventional EC probes, easy to operate, and sensitive to low solute concentrations. [ABSTRACT FROM AUTHOR]

The peptidoglycan (PG) layer is a critical component of the bacterial cell wall and serves as an important target for antibiotics in both gram-negative and gram-positive bacteria. The hydrolysis of septal PG (sPG) is a crucial step of bacterial cell division, facilitated by FtsEX through an amidase activation system. In this study, we present the cryo-EM structures of Escherichia coli FtsEX and FtsEX-EnvC in the ATP-bound state at resolutions of 3.05 Å and 3.11 Å, respectively. Our PG degradation assays in E. coli reveal that the ATP-bound conformation of FtsEX activates sPG hydrolysis of EnvC-AmiB, whereas EnvC-AmiB alone exhibits autoinhibition. Structural analyses indicate that ATP binding induces conformational changes in FtsEX-EnvC, leading to significant differences from the apo state. Furthermore, PG degradation assays of AmiB mutants confirm that the regulation of AmiB by FtsEX-EnvC is achieved through the interaction between EnvC-AmiB. These findings not only provide structural insight into the mechanism of sPG hydrolysis and bacterial cell division, but also have implications for the development of novel therapeutics targeting drug-resistant bacteria. The septal peptidoglycan hydrolysis machinery is a crucial structure for bacterial cell division. This study analyses the cryo-EM structure and enzymatic function of E. coli FtsEX, with and without the lytic-factor protein EnvC, characterizing the molecular basis of FtsEX regulation of peptidoglycan hydrolysis, which could be used to develop novel treatments targeting drug-resistant bacteria. [ABSTRACT FROM AUTHOR]

Background. Acute on chronic liver failure (ACLF) is a severe form of liver cell failure with high mortality rates. Hepatocyte cell death in ACLF can occur through necrosis or apoptosis. The M30 fragment of caspase-cleaved-cytokeratin 18 is a marker of caspase-mediated apoptosis. Objective: To assess serum caspase-cleaved CK 18 (M30) level as a diagnostic marker for acute-on-chronic liver failure (ACLF) in chronic hepatitis C cirrhosis patients. Furthermore, to determine the optimal cut-off level of serum caspase-cleaved CK 18 (M30) for diagnosing ACLF and its association with ACLF severity. Methods: The study involved 60 chronic HCV cirrhotic patients with ACLF (Group 1), 15 chronic HCV compensated cirrhotic patients (Group 2), and 15 healthy controls (Group 3). Laboratory tests and radiological assessments were conducted, including calculation of Child– Pugh score, MELD score, Consortium Liver Failure-Organ Failure (CLIF-OF) score, and CLIF-C-ACLF score using the EASL calculator. Serum level of caspase-cleaved CK 18 (M30) was measured using ELISA. Results: The serum level of caspase-cleaved CK 18 (M30) was significantly higher in group 1 compared to groups 2 and 3. Serum caspase-cleaved CK 18 (M30) showed a high predictive value for ACLF. At a cut-off level of 3.45 ng/ml, caspase-cleaved CK 18 (M30) had a sensitivity of 85% and specificity of 93.3% and AUC of 0.902 (95% CI = 0.833–0.970). There was a positive correlation between serum caspase-cleaved CK 18 (M30) levels and CLIF-C-ACLF score, indicating its potential as a predictor of ACLF severity. Conclusion. Serum caspase-cleaved CK 18 (M30), at cut off value of 3.45 ng/ml can accurately predict acute-on-chronic liver failure in patients with chronic HCV cirrhosis. Higher levels were associated with increased ACLF severity and mortality. [ABSTRACT FROM AUTHOR]

Colorectal cancer (CRC) is a major life-threatening disease, being the third most common cancer and a leading cause of death worldwide. Enhanced adiposity, particularly visceral fat, is a major risk factor for CRC, and obesity-associated alterations in metabolic, inflammatory and immune profiles in visceral adipose tissue (VAT) strongly contribute to promoting or sustaining intestinal carcinogenesis. The role of diet and nutrition in obesity and CRC has been extensively demonstrated, and AT represents the main place where diet-induced signals are integrated. Among the factors introduced with diet and processed or enriched in AT, ω3/ω6 polyunsaturated fatty acids (PUFAs) are endowed with pro- or anti-inflammatory properties and have been shown to exert either promoting or protective roles in CRC. In this study, we investigated the impact of ex vivo exposure to the ω3 and ω6 PUFAs docosahexaenoic and arachidonic acids on VAT adipocyte whole transcription in healthy lean, obese and CRC-affected individuals. High-throughput sequencing of protein-coding and long non-coding RNAs allowed us to identify specific pathways and regulatory circuits controlled by PUFAs and highlighted an impaired responsiveness of obese and CRC-affected individuals as compared to the strong response observed in healthy lean subjects. This further supports the role of healthy diets and balanced ω3/ω6 PUFA intake in the primary prevention of obesity and cancer. [ABSTRACT FROM AUTHOR]

Our study highlighted the immune changes by pro-inflammatory biomarkers in the gut–liver-axis-linked ROS-cell death mechanisms in chronic and acute inflammations when gut cells are exposed to endotoxins in patients with hepatic cirrhosis or steatosis. In duodenal tissue samples, gut immune barrier dysfunction was analyzed by pro-inflammatory biomarker expressions, oxidative stress, and cell death by flow cytometry methods. A significant innate and adaptative immune system reaction was observed as result of persistent endotoxin action in gut cells in chronic inflammation tissue samples recovered from hepatic cirrhosis with the A-B child stage. Instead, in patients with C child stage of HC, the endotoxin tolerance was installed in cells, characterized by T lymphocyte silent activation and increased Th1 cytokines expression. Interesting mechanisms of ROS-cell death were observed in chronic and acute inflammation samples when gut cells were exposed to endotoxins and immune changes in the gut–liver axis. Late apoptosis represents the chronic response to injury induction by the gut immune barrier dysfunction, oxidative stress, and liver-dysregulated barrier. Meanwhile, necrosis represents an acute and severe reply to endotoxin action on gut cells when the immune system reacts to pro-inflammatory Th1 and Th2 cytokines releasing, offering protection against PAMPs/DAMPs by monocytes and T lymphocyte activation. Flow cytometric analysis of pro-inflammatory biomarkers linked to oxidative stress-cell death mechanisms shown in our study recommends laboratory techniques in diagnostic fields. [ABSTRACT FROM AUTHOR]

Adjectives that are used to describe sensory experiences are often used to express more than one modality. The adjective sweet , for instance, may primarily be associated with taste (i.e., taste is the dominant modality of sweet), but it can also be used for smell, sound or sight, and possibly even for touch. It has also been shown that some sensory modalities combine more easily than others. Many adjectives that are used to describe taste, for instance, can also be used for smell, but, less likely, for sound. These associations between sensory modalities as they are expressed in language are the topic of this study. We looked at the distribution of the combinations of dominant modalities in pairs of antonymic sensory adjectives (e.g., sweet–sour), and how the dominant modality of the adjectives in these pairs differed from that of the adjectives in isolation. In our dataset, there was a sizeable number of pairs consisting of adjectives with differing dominant modalities. Within those pairs, we observed that adjectives with the dominant modality sight can also be used for touch and vice versa. Similarly, adjectives with the dominant modality of smell can also be used for taste and vice versa. Finally, adjectives with the dominant modalities sight and touch can both also be used for hearing and for taste, but not the other way around. These results contribute to our understanding of how language is used to describe sensory experiences, and, with that, how sensory experiences may be shaped by the words that we use to describe them. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to examine the prevalence of hypertension in Korean adolescents, its long-term trends, and factors associated with the development of hypertension. Methods: Data of the Korea National Health and Nutrition Examination Survey (KNHANES) from 2007 to 2020 were combined into three time periods (2007–2011, 2012–2016, and 2017–2020). A total of 11,146 Korean adolescents aged 10–18 were included in the analysis. The definition of hypertension was based on the 2017 American Academy of Pediatrics guidelines for hypertension. Results: The age-adjusted prevalence of hypertension was 5.47%, 7.85%, and 9.92% in 2007–2011, 2012–2016, and 2017–2020, respectively. Long-term trend analysis using Joinpoint analysis over the observation period showed a significantly increasing trend in hypertension prevalence with a mean annual percentage change of 6.4%. Boys, those aged 13–15, those aged 16–18, overweight/obese, and those living in urban areas were more likely to develop hypertension (OR 1.980, 1.492, 3.180, 2.943, and 1.330, respectively). Conclusion: The prevalence of hypertension in Korean adolescents was higher than the global prevalence of hypertension and showed an increase over a 13–year period. Targeted strategies for prevention and early detection of hypertension are needed in this population. [ABSTRACT FROM AUTHOR]

Preservation of executive function, like inhibition, closely links to the quality of life in senior adults. Although neuroimaging literature has shown enhanced inhibitory function followed by aerobic exercise, current evidence implies inconsistent neuroplasticity patterns along different time durations of exercise. Hence, we conducted a 12-week exercise intervention on 12 young and 14 senior volunteers and repeatedly measured the inhibitory functionality of distinct aspects (facilitation and interference effects) using the numerical Stroop task and functional Magnetic Resonance Imaging. Results showcased improved accuracy and reduced reaction times (RT) after 12-week exercise, attributed to frontoparietal and default mode network effects. In young adults, the first phase (0 to six weeks) exercise increased the activation of the right superior medial frontal gyrus, associated with reduced RT in interference, but in the second intervention phase (six to twelve weeks), the decreased activation of the left superior medial frontal gyrus positively correlated with reduced RT in facilitation. In senior adults, the first six-week intervention led to reduced activations of the inferior frontal gyrus, inferior parietal gyrus, and default mode network regions, associated with the reduced RT in interference. Still, in the second intervention phase, only the visual area exhibited increased activity, associated with reduced RT in interference. Except for the distinctive brain plasticity between the two phases of exercise intervention, the between-group comparison also presented that the old group gained more cognitive benefits within the first six weeks of exercise intervention; however, the cognitive improvements in the young group occurred after six weeks of intervention. Limited by the sample size, these preliminary findings corroborated the benefits of aerobic exercise on the inhibitory functions, implying an age × exercise interaction on the brain plasticity for both facilitation and interference. [ABSTRACT FROM AUTHOR]

There is a current lack of consensus on whether the ancestral parity mode was oviparity (egg-laying) or viviparity (live-birth) in amniotes and particularly in squamates (snakes, lizards, and amphisbaenids). How transitions between parity modes occur at the genomic level has primary importance for how science conceptualises the origin of amniotes, and highly variable parity modes in Squamata. Synthesising literature from medicine, poultry science, reproductive biology, and evolutionary biology, I review the genomics and physiology of five broad processes (here termed the 'Main Five') expected to change during transitions between parity modes: eggshell formation, embryonic retention, placentation, calcium transport, and maternal-fetal immune dynamics. Throughout, I offer alternative perspectives and testable hypotheses regarding proximate causes of parity mode evolution in amniotes and squamates. If viviparity did evolve early in the history of lepidosaurs, I offer the nucleation site hypothesis as a proximate explanation. The framework of this hypothesis can be extended to amniotes to infer their ancestral state. I also provide a mechanism and hypothesis on how squamates may transition from viviparity to oviparity and make predictions about the directionality of transitions in three species. After considering evidence for differing perspectives on amniote origins, I offer a framework that unifies (i) the extended embryonic retention model and (ii) the traditional model which describes the amniote egg as an adaptation to the terrestrial environment. Additionally, this review contextualises the origin of amniotes and parity mode evolution within Medawar's paradigm. Medawar posited that pregnancy could be supported by immunosuppression, inertness, evasion, or immunological barriers. I demonstrate that this does not support gestation or gravidity across most amniotes but may be an adequate paradigm to explain how the first amniote tolerated internal fertilization and delayed egg deposition. In this context, the eggshell can be thought of as an immunological barrier. If serving as a barrier underpins the origin of the amniote eggshell, there should be evidence that oviparous gravidity can be met with a lack of immunological responses in utero. Rare examples of two species that differentially express very few genes during gravidity, suggestive of an absent immunological reaction to oviparous gravidity, are two skinks Lampropholis guichenoti and Lerista bougainvillii. These species may serve as good models for the original amniote egg. Overall, this review grounds itself in the historical literature while offering a modern perspective on the origin of amniotes. I encourage the scientific community to utilise this review as a resource in evolutionary and comparative genomics studies, embrace the complexity of the system, and thoughtfully consider the frameworks proposed., (© 2024 Cambridge Philosophical Society.)

Metabolic dysfunction-associated steatohepatitis (MASH, previously termed non-alcoholic steatohepatitis (NASH)), is a major complication of obesity that promotes fatty liver disease. MASH is characterized by progressive tissue fibrosis and sterile liver inflammation that can lead to liver cirrhosis, cancer, and death. The molecular mechanisms of fibrosis in MASH and its systemic control remain poorly understood. Here, we identified the secreted-type pro-fibrotic protein, procollagen C-endopeptidase enhancer-1 (PCPE-1), as a brown adipose tissue (BAT)-derived adipokine that promotes liver fibrosis in a murine obesity-induced MASH model. BAT-specific or systemic PCPE-1 depletion in mice ameliorated liver fibrosis, whereas, PCPE-1 gain of function in BAT enhanced hepatic fibrosis. High-calorie diet-induced ER stress increased PCPE-1 production in BAT through the activation of IRE-1/JNK/c-Fos/c-Jun signaling. Circulating PCPE-1 levels are increased in the plasma of MASH patients, suggesting a therapeutic possibility. In sum, our results uncover PCPE-1 as a novel systemic control factor of liver fibrosis., (© 2024. The Author(s).)

Introduction: Real-time fMRI-based neurofeedback (rt-fMRI-NFB) is a noninvasive technology that enables individuals to self-regulate brain activity linked to neuropsychiatric symptoms, including those associated with post-traumatic stress disorder (PTSD). Selecting the target brain region for neurofeedbackmediated regulation is primarily informed by the neurobiological characteristics of the participant population. There is a strong link between PTSD symptoms and multiple functional disruptions in the brain, including hyperactivity within both the amygdala and posterior cingulate cortex (PCC) during trauma-related processing. As such, previous rt-fMRI-NFB studies have focused on these two target regions when training individuals with PTSD to regulate neural activity. However, the differential effects of neurofeedback target selection on PTSD-related neural activity and clinical outcomes have not previously been investigated. Methods: Here, we compared whole-brain activation and changes in PTSD symptoms between PTSD participants (n  =  28) that trained to downregulate activity within either the amygdala (n  =  14) or the PCC (n  =  14) while viewing personalized trauma words. Results: For the PCC as compared to the amygdala group, we observed decreased neural activity in several regions implicated in PTSD psychopathology – namely, the bilateral cuneus/precuneus/primary visual cortex, the left superior parietal lobule, the left occipital pole, and the right superior temporal gyrus/temporoparietal junction (TPJ) – during target region downregulation using rt-fMRI-NFB. Conversely, for the amygdala as compared to the PCC group, there were no unique (i.e., over and above that of the PCC group) decreases in neural activity. Importantly, amygdala downregulation was not associated with significantly improved PTSD symptoms, whereas PCC downregulation was associated with reduced reliving and distress symptoms over the course of this single training session. In this pilot analysis, we did not detect significant between-group differences in state PTSD symptoms during neurofeedback. As a critical control, the PCC and amygdala groups did not differ in their ability to downregulate activity within their respective target brain regions. This indicates that subsequent whole-brain neural activation results can be attributed to the effects of the neurofeedback target region selection in terms of neurophysiological function, rather than as a result of group differences in regulatory success. Conclusion: In this study, neurofeedback-mediated downregulation of the PCC was differentially associated with reduced state PTSD symptoms and simultaneous decreases in PTSD-associated brain activity during a single training session. This novel analysis may guide researchers in choosing a neurofeedback target region in future rt-fMRI-NFB studies and help to establish the clinical efficacy of specific neurofeedback targets for PTSD. A future multi-session clinical trial of rt-fMRI-NFB that directly compares between PCC and amygdala target regions is warranted. [ABSTRACT FROM AUTHOR]

The study aims to analyze the relationship between central obesity and the risk of hypertension in obese adolescents, including both male and female subjects. The study was a retrospective observational study that utilized medical record data from a previous research project entitled "Polimorfisme Gen Adiponectin ADIPOQ +45 T>G, ADIPOQ – 11377 C>G with Adiponectin Levels in Obese Adolescents and Risk of Metabolic Syndrome." This data was obtained from research conducted on obese adolescents aged 13-18 years in junior and senior high schools in Surabaya and Sidoarjo who met the criteria. The sample comprised 140 obese adolescents, who were then categorized into two groups: those without central obesity and those with central obesity. Statistical data were analyzed using SPSS with the Chi Square test. There is a very strong and significant relationship between central obesity and the risk of hypertension in obese adolescents (p = 0.000; r = 0.373); central obesity and the risk of hypertension in obese male adolescents (p = 0.001; r = 0.587); and central obesity and the risk of hypertension in obese female adolescents (p = 0.003; r = 0.300). The study found a significant relationship between central obesity and hypertension risk in obese adolescents. Adolescents with central obesity were 3.6 times more likely to develop hypertension than those without. Male adolescents with central obesity were 6.5 times more likely to develop hypertension than those without. Female adolescents with central obesity were 2.9 times more likely to develop hypertension. [ABSTRACT FROM AUTHOR]

INTRODUCTION Smoking tobacco results in the death of more than 8 million people every year. Our study aims to explore a new approach for smoking cessation by analyzing body composition differences between smokers and non-smokers, focusing on potential variations in biological and chronological ages. METHODS A cross-sectional study was conducted in 2019 at the Special Hospital for Medical Rehabilitation in Croatia. It included 164 subjects, 81 smokers and 83 non-smokers, aged 40-65 years. This study was part of a two-year investigation on locomotor parameter changes as early COPD predictors. Measurements encompassed body parameters, spirometry tests, and body composition. Spirometry was done using the Flowscreen Pro device, and the FEV1/FVC ratio determined lung function. The GAIA 359 PLUS device assessed body composition and estimated biological age. Exclusion criteria applied to specific medical conditions and recent surgeries. RESULTS Smokers had a slightly higher percentage of fat tissue than non-smokers (median=27%, IQR: 24-31) compared to non-smokers (median=25%, IQR: 22-28, p<0.001). The difference in the Gaia estimated age and the actual age of the subjects was significantly higher in the group of smokers (median=2, IQR: 0-3) compared to non-smokers (median=0 IQR: -2-2, p=0.003), but they did not differ in muscle tissue, weight or the proportion of trunk adipose tissue. CONCLUSIONS Our study revealed that smokers exhibit higher fat tissue percentages and a higher estimated biological age relative to non-smokers. These findings underscore the established health hazards of smoking and the imperative for smoking cessation in mitigating these adverse effects. [ABSTRACT FROM AUTHOR]

Pseudomonas aeruginosa is an opportunistic pathogen that can cause infections in humans, especially in hospital patients with compromised host defence mechanisms, including patients with cystic fibrosis. Filamentous bacteriophages represent a group of single-stranded DNA viruses infecting different bacteria, including P. aeruginosa and other human and animal pathogens; many of them can replicate when integrated into the bacterial chromosome. Filamentous bacteriophages can contribute to the virulence of P. aeruginosa and influence the course of the disease. There are just a few isolated and officially classified filamentous bacteriophages infecting P. aeruginosa, but genomic studies indicated the frequent occurrence of integrated prophages in many P. aeruginosa genomes. An analysis of sequenced genomes of P. aeruginosa isolated from upper respiratory tract (throat and nasal swabs) and sputum specimens collected from Russian patients with cystic fibrosis indicated a higher diversity of filamentous bacteriophages than first thought. A detailed analysis of predicted bacterial proteins revealed prophage regions representing the filamentous phages known to be quite distantly related to known phages. Genomic comparisons and phylogenetic studies enabled the proposal of several new taxonomic groups of filamentous bacteriophages. [ABSTRACT FROM AUTHOR]

Although the frequency of myocarditis in the general population is very difficult to accurately determine due to the large number of asymptomatic cases, the incidence of this disease is increasing significantly due to better defined criteria for diagnosis and the development of modern diagnostic methods. The multitude of different etiological factors, the diversity of the clinical picture, and the variability of the diagnostic findings make this disease often demanding both for the selection of the diagnostic modality and for the proper therapeutic approach. The previously known most common viral etiology of this disease is today overshadowed by new findings based on immune-mediated processes, associated with diseases that in their natural course can lead to myocardial involvement, as well as the iatrogenic cause of myocarditis, which is due to use of immune checkpoint inhibitors in the treatment of cancer patients. Suspecting that a patient with polymorphic and non-specific clinical signs and symptoms, such as changes in ECG and echocardiography readings, has myocarditis is the starting point in the diagnostic algorithm. Cardio magnetic resonance imaging is non-invasive and is the gold standard for diagnosis and clinical follow-up of these patients. Endomyocardial biopsy as an invasive method is the diagnostic choice in life-threatening cases with suspicion of fulminant myocarditis where the diagnosis has not yet established or there is no adequate response to the applied therapeutic regimen. The treatment of myocarditis is increasingly demanding and includes conservative methods of treating heart failure, immunomodulatory and immunospressive therapy, methods of mechanical circulatory support, and heart transplantation. The goal of developing new diagnostic and therapeutic methods is to reduce mortality from this complex disease, which is still high. [ABSTRACT FROM AUTHOR]

Restoration of natural processes in ecosystems is key to mitigate the biodiversity crisis. Here, we evaluate 20 Danish stream‐valley restoration projects—mainly by rewetting—in terms of successful restoration of natural wetland habitats. We used quadratic discriminant analysis and generalized linear models to compare 80 vegetation plots from the restoration projects with >60,000 natural or semi‐natural wetland reference plots. We modeled the influence of time since restoration, grazing, rewetting, and nutrient availability on (1) the probability that study plots belong to natural habitats and (2) their richness of high‐quality‐habitat indicator species. The probability of a restored wetland having developed into a natural wetland habitat—such as an alkaline fen—was generally below 10%. Also, we found only half as many indicator species in restored wetlands than in reference wetlands and we demonstrated that the number of characteristic alkaline fen species did not deviate from what could be expected under the prevailing nutrient conditions. We found a negative effect of soil nutrient availability on the number of high‐quality‐habitat indicator species and the lowest probability of plots being natural wetlands in the most nutrient rich plots. The effect of grazing was only positive in the first years after restoration and only in the most nutrient rich plots, while the effect of rewetting sites to historical hydrological conditions was generally negative. Our findings suggest that unnaturally high nutrient availability is probably the core limiting factor for successful restoration of natural wetlands and their associated plant diversity. [ABSTRACT FROM AUTHOR]

Primary visual cortex (V1) is generally thought of as a low-level sensory area that primarily processes basic visual features. Although there is evidence for multisensory effects on its activity, these are typically found for the processing of simple sounds and their properties, for example spatially or temporally-congruent simple sounds. However, in congenitally blind individuals, V1 is involved in language processing, with no evidence of major changes in anatomical connectivity that could explain this seemingly drastic functional change. This is at odds with current accounts of neural plasticity, which emphasize the role of connectivity and conserved function in determining a neural tissue's role even after atypical early experiences. To reconcile what appears to be unprecedented functional reorganization with known accounts of plasticity limitations, we tested whether V1's multisensory roles include responses to spoken language in sighted individuals. Using fMRI, we found that V1 in normally sighted individuals was indeed activated by comprehensible spoken sentences as compared to an incomprehensible reversed speech control condition, and more strongly so in the left compared to the right hemisphere. Activation in V1 for language was also significant and comparable for abstract and concrete words, suggesting it was not driven by visual imagery. Last, this activation did not stem from increased attention to the auditory onset of words, nor was it correlated with attentional arousal ratings, making general attention accounts an unlikely explanation. Together these findings suggest that V1 responds to spoken language even in sighted individuals, reflecting the binding of multisensory high-level signals, potentially to predict visual input. This capability might be the basis for the strong V1 language activation observed in people born blind, re-affirming the notion that plasticity is guided by pre-existing connectivity and abilities in the typically developed brain. [ABSTRACT FROM AUTHOR]

We have previously demonstrated that deletion of an intracellular leucine aminopeptidase results in attenuated virulence of S. aureus. Herein we explore the role of 10 other aminopeptidases in S. aureus pathogenesis. Using a human blood survival assay we identified mutations in two enzymes from the M20B family (PepT1 and PepT2) as having markedly decreased survival compared to the parent. We further reveal that pepT1, pepT2 and pepT1/2 mutant strains are impaired in their ability to resist phagocytosis by, and engender survival within, human macrophages. Using a co-infection model of murine sepsis, we demonstrate impairment of dissemination and survival for both single mutants that is even more pronounced in the double mutant. We show that these enzymes are localized to the cytosol and membrane but are not necessary for peptide-based nutrition, a hallmark of cell-associated aminopeptidases. Furthermore, none of the survival defects appear to be the result of altered virulence factor production. An exploration of their regulation reveals that both are controlled by known regulators of the S. aureus virulence process, including Agr, Rot and/or SarA, and that this cascade may be mediated by FarR. Structural modeling of PepT1 reveals it bears all the hallmarks of a tripeptidase, whilst PepT2 differs significantly in its catalytic pocket, suggesting a broader substrate preference. In sum, we have identified two M20B aminopeptidases that are integral to S. aureus pathogenesis. The future identification of protein and/or peptide targets for these proteases will be critical to understanding their important virulence impacting functions. [ABSTRACT FROM AUTHOR]

Unlike other adverse drug reactions, visceral organ involvement is a prominent feature of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome and correlates with mortality. The aim of this study was to systematically review cases published in PubMed-indexed, peer-reviewed journals in which patients had renal injury during the episode of DRESS syndrome (DS). We found 71 cases, of which 67 were adults and 56% were males. Female sex was associated with higher mortality. Chronic kidney disease (CKD) was present in 14% of patients who developed acute kidney injury (AKI) during DS. In 21% of cases, the kidneys were the only visceral organ involved, while 54% of patients had both liver and kidney involvement. Eosinophilia was absent in 24% of patients. The most common classes of medication associated with renal injury in DS were antibiotics in 34%, xanthine oxidase inhibitors in 15%, and anticonvulsants in 11%. Among antibiotics, vancomycin was the most common culprit in 68% of patients. AKI was the most common renal manifestation reported in 96% of cases, while isolated proteinuria or hematuria was present in only 4% of cases. In cases with AKI, 88% had isolated increase in creatinine and decrease in glomerular filtration (GFR), 27% had AKI concomitantly with proteinuria, 18% had oliguria, and 13% had concomitant AKI with hematuria. Anuria was the rarest manifestation, occurring in only 4% of patients with DS. Temporary renal replacement therapy was needed in 30% of cases, and all but one patient fully recovered renal function. Mortality of DS in this cohort was 13%, which is higher than previously reported. Medication class, latency period, or pre-existing CKD were not found to be associated with higher mortality. More research, particularly prospective studies, is needed to better recognize the risks associated with renal injury in patients with DS. The development of disease-specific biomarkers would also be useful so DS with renal involvement can be easier distinguished from other eosinophilic diseases that might affect the kidney. [ABSTRACT FROM AUTHOR]

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Asian carp (bighead carp, Hypophthalmichthys nobilis; grass carp, Ctenopharyngodon idella and silver carp, H. molitrix) are a group of invasive species that are predicted to cause ecological effects if they invade the Great Lakes basin. Although Asian carp age at maturity is known to be an important factor in the risk of establishing a population, there is relatively little maturity data for North America. We found that air temperature can be used to predict the age at maturity of Asian carp. Nonlinear regressions using mean annual air temperature and annual degree days to predict age at maturity explain 60% and 62% of the variation respectively. These models predict that maturation is possible in locations that were previously excluded from Asian carp spawning range based on data from the Amur River. As expected, we find faster maturation in more southern areas of North America, although there are relatively large errors predicting age at maturity in the Mississippi River population. We conclude that due to the effect of faster maturation on population growth rates, southern Great Lakes locations (e.g. Lake Erie) may be at greater risk of faster population establishment. [ABSTRACT FROM AUTHOR]

Memory for words that are drawn or sketched by the participant, rather than written, during encoding is typically superior. While this drawing benefit has been reliably demonstrated in recent years, there has yet to be an investigation of its neural basis. Here, we asked participants to either create drawings, repeatedly write, or list physical characteristics depicting each target word during encoding. Participants then completed a recognition memory test for target words while undergoing functional magnetic resonance imaging (fMRI). Behavioural results showed memory was significantly higher for words drawn than written, replicating the typical drawing effect. Memory for words whose physical characteristics were listed at encoding was also higher than for those written repeatedly, but lower than for those drawn. Voxel-wise analyses of fMRI data revealed two distributed sets of brain regions more active for items drawn relative to written, the left angular gyrus (BA 39) and bilateral frontal (BA 10) regions, suggesting integration and self-referential processing during retrieval of drawn words. Brain-behaviour correlation analyses showed that the size of one's memory benefit for words drawn relative to written at encoding was positively correlated with activation in brain regions linked to visual representation and imagery (BA 17 and cuneus) and motor planning (premotor and supplementary motor areas; BA 6). This study suggests that drawing benefits memory by coactivating multiple sensory traces. Target words drawn during encoding are subsequently remembered by re-engaging visual, motoric, and semantic representations., (© 2024. The Psychonomic Society, Inc.)

Pseudomonas aeruginosa is a model quorum sensing (QS) pathogen with three interconnected QS circuits that control the production of virulence factors and antibiotic tolerant biofilms. The pqs QS system of P. aeruginosa is responsible for the biosynthesis of diverse 2-alkyl-4-quinolones (AQs), of which 2-heptyl-4-hydroxyquinoline (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS) function as QS signal molecules. Transcriptomic analyses revealed that HHQ and PQS influenced the expression of multiple genes via PqsR-dependent and -independent pathways whereas 2-heptyl-4-hydroxyquinoline N-oxide (HQNO) had no effect on P. aeruginosa transcriptome. HQNO is a cytochrome bc1 inhibitor that causes P. aeruginosa programmed cell death and autolysis. However, P. aeruginosa pqsL mutants unable to synthesize HQNO undergo autolysis when grown as colony biofilms. The mechanism by which such autolysis occurs is not understood. Through the generation and phenotypic characterization of multiple P. aeruginosa PAO1 mutants producing altered levels of AQs in different combinations, we demonstrate that mutation of pqsL results in the accumulation of HHQ which in turn leads to Pf4 prophage activation and consequently autolysis. Notably, the effect of HHQ on Pf4 activation is not mediated via its cognate receptor PqsR. These data indicate that the synthesis of HQNO in PAO1 limits HHQ-induced autolysis mediated by Pf4 in colony biofilms. A similar phenomenon is shown to occur in P. aeruginosa cystic fibrosis (CF) isolates, in which the autolytic phenotype can be abrogated by ectopic expression of pqsL. [ABSTRACT FROM AUTHOR]

Combined hepatocellular-cholangiocarcinoma (cHCC-CC) is a rare type of primary liver cancer. It is a complex "biphenotypic" tumor type consisting of bipotential hepatic progenitor cells that can differentiate into cholangiocytes subtype and hepatocytes subtype. The prognosis of patients with cHCC-CC is quite poor with its specific and more aggressive nature. Furthermore, there are no definite demographic or clinical features of cHCC-CC, thus a clear preoperative identification and accurate non-invasive imaging diagnostic analysis of cHCC-CC are of great value. In this review, we first summarized the epidemiological features, pathological findings, molecular biological information and serological indicators of cHCC-CC disease. Then we reviewed the important applications of non-invasive imaging modalities-particularly ultrasound (US)-in cHCC-CC, covering both diagnostic and prognostic assessment of patients with cHCC-CC. Finally, we presented the shortcomings and potential outlooks for imaging studies in cHCC-CC. [ABSTRACT FROM AUTHOR]

Obesity (Ob), which has dramatically increased in the last decade, is one of the main risk factors that contribute to the incidence and progression of osteoarthritis (OA). Targeting the characteristics of obesity-associated osteoarthritis (ObOA) may offer new chances for precision medicine strategies in this patient cohort. First, this review outlines how the medical perspective of ObOA has shifted from a focus on biomechanics to the significant contribution of inflammation, mainly mediated by changes in the adipose tissue metabolism through the release of adipokines and the modification of fatty acid (FA) compositions in joint tissues. Preclinical and clinical studies on n-3 polyunsaturated FAs (PUFAs) are critically reviewed to outline the strengths and weaknesses of n-3 PUFAs' role in alleviating inflammatory, catabolic and painful processes. Emphasis is placed on potential preventive and therapeutic nutritional strategies based on n-3 PUFAs, with a focus on ObOA patients who could specifically benefit from reformulating the dietary composition of FAs towards a protective phenotype. Finally, tissue engineering approaches that involve the delivery of n-3 PUFAs directly into the joint are explored to address the perspectives and current limitations, such as safety and stability issues, for implementing preventive and therapeutic strategies based on dietary compounds in ObOA patients. [ABSTRACT FROM AUTHOR]

Increases in chicken production are mainly due to specialised breeds. However, local breeds are of increasing importance, known for ability to adapt to the environment and unique products. Conventional poultry products contain lower levels of n‐3 fatty acids (FAs) compared to those obtained from local breeds, therefore the aim of this study was to evaluate the modulation of expression of genes involved in long‐chain polyunsaturated FA (PUFA) biosynthesis pathways according to genetic background, diet conditions, and sex. Animals from two local breeds and a commercial line were fed different diets: control and experimental diet (10% linseed supplementation). For each breed and diet group, both sexes were reared. The RNA was extracted from 36 liver samples and sequenced by RNAseq method. Bioinformatic analysis was carried out to find differentially expressed genes from comparisons between experimental groups. Results showed low impact of diet on differentially expressed genes related to FA biosynthesis, but linseed diet increased percentage of n‐3 FAs of liver. Sex and genetic background determined the differential expression of genes related to long‐chain PUFA biosynthesis. Specifically, females of local breeds shared 23 up‐regulated genes when compared to their respective commercial line groups. Some of the shared genes had a role in de novo triglyceride biosynthesis (MTTPL and GPAM), and in de novo FA biosynthesis (ACACA and SCD) was detected. In conclusion, local breeds are able to better adapt to a diet rich in PUFA, by triggering certain transcriptomic shifts in the liver that allow birds to process the high PUFA content provided by diet. [ABSTRACT FROM AUTHOR]

One area of cancer research is the interaction between cancer cells and immune cells, in which chemokines play a vital role. Despite this, a comprehensive summary of the involvement of C-X-C motif ligand 1 (CXCL1) chemokine (also known as growth-regulated gene-α (GRO-α), melanoma growth-stimulatory activity (MGSA)) in cancer processes is lacking. To address this gap, this review provides a detailed analysis of CXCL1's role in gastrointestinal cancers, including head and neck cancer, esophageal cancer, gastric cancer, liver cancer (hepatocellular carcinoma (HCC)), cholangiocarcinoma, pancreatic cancer (pancreatic ductal adenocarcinoma), and colorectal cancer (colon cancer and rectal cancer). This paper presents the impact of CXCL1 on various molecular cancer processes, such as cancer cell proliferation, migration, and invasion, lymph node metastasis, angiogenesis, recruitment to the tumor microenvironment, and its effect on immune system cells, such as tumor-associated neutrophils (TAN), regulatory T (Treg) cells, myeloid-derived suppressor cells (MDSCs), and macrophages. Furthermore, this review discusses the association of CXCL1 with clinical aspects of gastrointestinal cancers, including its correlation with tumor size, cancer grade, tumor–node–metastasis (TNM) stage, and patient prognosis. This paper concludes by exploring CXCL1's potential as a therapeutic target in anticancer therapy. [ABSTRACT FROM AUTHOR]

Background/Aim: Cardiovascular disease (CVD) is a frequent complication in hemodialysis (HD) patients, especially when the underlying disease is diabetes mellitus (DM). In this study, we investigated cardiovascular events and lipid and fatty acid profile in maintenance HD patients with diabetic kidney disease (DKD). Patients and Methods: The subjects were 123 patients undergoing HD at Oyokyo Kidney Research Institute Hirosaki Hospital, who were considered to have DKD as the underlying cause of dialysis induction. Among these patients, the lipid and fatty acid profile were examined in two groups, CVD group (n=53) and non-CVD group (n=70), according to the presence or absence of a history of cardiovascular events (coronary artery disease, stroke, arteriosclerosis obliterans, valvular disease, and aortic disease). For serum lipid profile, the levels of total-cholesterol (T-C), triglycerides (TG), high density lipoprotein-cholesterol (HDL-C), and low density lipoprotein-cholesterol (LDL-C) were measured, and for fatty acid balance, 24 fractions of fatty acid composition in plasma total lipids were measured. These markers were compared between the CVD and non-CVD groups. Results: The levels of T-C and TG were significantly lower in the CVD group compared with the non-CVD group (147.7±36.9 mg/dl vs. 159.2±35.6 mg/dl, p<0.05, 120.2±65.7 mg/dl vs. 143.8±124.4 mg/dl, p<0.05). In the plasma fatty acid composition, alpha-linolenic acid (ALA) and docosapentaenoic acid (DPA) were significantly lower in the CVD group compared with the non-CVD group (0.74±0.26 wt% vs. 0.84±0.31 wt%, p<0.05; 0.61±0.21 wt% vs. 0.70±0.30 wt%, p<0.05). Conclusion: Abnormal fatty acid balance, especially low levels of ALA and DPA, rather than serum lipids, are more likely the factors associated with cardiovascular events in maintenance HD patients with underlying DKD. [ABSTRACT FROM AUTHOR]

The deployment of artificial structures in streambeds has been proposed as a way to enhance 21 hyporheic exchange, and numerical models can be used to quantify their effects. In this study, combinations of different structures—that is, boxes, steps and a new type of subsurface structure (L‐shaped structure)—were considered to evaluate their potential applicability on river restoration. Flow‐3D and COMSOL were applied to simulate surface and subsurface flow, respectively. The performance of the structures was evaluated on the basis of hyporheic flow and residence time distributions. For the structure sizes here considered, results showed for steps (single step, combination of two steps) and L‐shaped structures (single L‐shaped structure, combination of two L‐shaped structures) most hyporheic flowpaths return to the stream after 5 and 2.5 hr, respectively. Instead, shorter residence times (<0.25 hr) were found for boxes (single box, combination of two boxes). For combinations of steps and permeable boxes, the values of hyporheic flow per unit width are higher (0.35 and 0.3 m2/hr, respectively) than for the combination of L‐shaped (0.06 m2/hr). As a result, the combinations of steps and boxes are more effective in increasing hyporheic flow. However, when subsurface structures are combined with steps the resulting hyporheic exchange is dominated by the steps. Therefore, the combined use of in‐stream and subsurface structures separately may increase their benefits for hyporheic exchange, but when steps are the other subsurface structures provide minor advantages. Key Points: We modeled hyporheic flow induced by steps, L‐shaped structures and boxesSteps and boxes drive more hyporheic flow, while steps and L‐shaped structures have longer residence timesWhen different types of structures are deployed together, hyporheic flow and residence times are controlled by steps [ABSTRACT FROM AUTHOR]

We investigated the association between obesity and cardiovascular disease risk factors (CVDRFs) in adolescents. We performed a cross-sectional study using the data from 8149 adolescents, aged 10–18 years, included in the Korean National Health and Nutrition Examination Survey (2011–2020). Using the body mass index, we defined "overweight" (≥85th to <95th percentile) and "obese" (≥95th percentile). We analyzed the associations between obesity and CVDRFs (high blood pressure, abnormal lipid profiles, and high fasting glucose levels) by sex and age groups (early [10–12 years], middle [13–15 years], and late [16–18 years] adolescence). When analyzing all the subjects, being overweight was correlated with high blood pressure and abnormal all-lipid profiles in boys and high triglyceride and low high-density lipoprotein cholesterol levels in girls, while obesity was associated with all CVDRFs in both boys and girls. Analyzing separately in the age subgroups, the correlation between obesity and CVDRFs tended to be shown earlier in boys than in girls, and obesity tended to be associated with CVDRFs earlier than being overweight. The association between obesity and CVDRFs may begin to be shown at different periods of youth, depending on the degree of obesity, CVDRF variables, and sex. [ABSTRACT FROM AUTHOR]

Rare cases of Pseudomonas aeruginosa community-acquired pneumonia (PA-CAP) were reported in non-immunocompromised patients. We describe a case of Pseudomonas aeruginosa (PA) necrotizing cavitary CAP with a fatal outcome in a 53-year-old man previously infected with SARS-CoV-2, who was admitted for dyspnea, fever, cough, hemoptysis, acute respiratory failure and a right upper lobe opacification. Six hours after admission, despite effective antibiotic therapy, he experienced multi-organ failure and died. Autopsy confirmed necrotizing pneumonia with alveolar hemorrhage. Blood and bronchoalveolar lavage cultures were positive for PA serotype O:9 belonging to ST1184. The strain shares the same virulence factor profile with reference genome PA01. With the aim to better investigate the clinical and molecular characteristics of PA-CAP, we considered the literature of the last 13 years concerning this topic. The prevalence of hospitalized PA-CAP is about 4% and has a mortality rate of 33–66%. Smoking, alcohol abuse and contaminated fluid exposure were the recognized risk factors; most cases presented the same symptoms described above and needed intensive care. Co-infection of PA-influenza A is described, which is possibly caused by influenza-inducing respiratory epithelial cell dysfunction: the same pathophysiological mechanism could be assumed with SARS-CoV-2 infection. Considering the high rate of fatal outcomes, additional studies are needed to identify sources of infections and new risk factors, along with genetic and immunological features. Current CAP guidelines should be revised in light of these results. [ABSTRACT FROM AUTHOR]

There has been a steady rise in the incidence of cardiovascular disease (CVD) in the Iranian population. The aim of this study is to investigate the association between Global Dietary Index (GDI) and CVD risk among the Iranian adult population. This study was conducted based on Isfahan Cohort Study, a longitudinal study that collected data between 2001 and 2013 on 6405 adults. Dietary intakes were assessed by a validated food frequency questionnaire to calculate GDI. All participants were followed every two years by phone call to ask about death, any hospitalization, or cardiovascular events to examine CVD events. The Average age of participants was 50.70 ± 11.63 and the median of GDI score was 1 (IQR: 0.29). A total of 751 CVD events (1.4 incidence rate, per 100 person-year) occurred during 52,704 person-years of follow-up. One-unit GDI increase was associated with a higher risk of MI by 72% (HR: 1.72; 95% CI 1.04–2.84), stroke by 76% (HR: 1.76; 95% CI 1.09–2.85) and CVD by 30% (HR: 1.48; 95% CI 1.02–2.65). In addition, a one-unit GDI increase was associated with a higher risk of coronary heart disease more than 2 times (HR: 2.32; 95% CI 1.50–3.60) and CVD mortality and all-cause mortality over than 3 times [(HR: 3.65; 95% CI 1.90–7.01) and (HR: 3.10; 95% CI 1.90–5.06), respectively]. Higher GDI had a significant relationship with the increased risk of CVD events and all-cause mortality. Further epidemiological studies in other populations are suggested to confirm our findings. [ABSTRACT FROM AUTHOR]

According to the prevailing view, cognitive processes of mental rotation are carried out by visuospatial perceptual circuits located primarily in high cortical areas. Here, we examined the functional involvement of (mostly subcortical) monocular channels in mental rotation tasks. Images of two rotated objects (0°, 50°, 100°, or 150°; identical or mirrored) were presented either to one eye (monocular) or segregated between the eyes (interocular). The results indicated a causal role for low monocular visual channels in mental rotation: Response times for identical ("same") objects at high angular disparities (100°, 150°) were shorter when both objects were presented to a single eye than when each object was presented to a different eye. We suggest that mental rotation processes rely on cortico-subcortical loops that support visuospatial perception. More generally, the findings highlight the potential contribution of lower-level mechanisms to what are typically considered to be high-level cognitive functions, such as mental representation. [ABSTRACT FROM AUTHOR]

A genetic risk score (GRS) predictive of the plasma triglyceride (TG) response to an omega-3 fatty acid (n-3 FA) supplementation has been previously developed in the Fatty Acid Sensor (FAS) Study. Recently, novel single nucleotide polymorphisms (SNPs) interacting with a fish oil supplementation and associated with plasma lipid levels have been identified in the UK Biobank. The aim of this study was to verify whether the addition of SNPs identified in the UK Biobank to the GRS built in the FAS Study improves its capacity to predict the plasma TG response to an n-3 FA supplementation. SNPs interacting with fish oil supplementation in the modulation of plasma lipid levels in the UK Biobank and associated with plasma TG levels have been genotyped in participants of the FAS Study (n = 141). Participants have been supplemented with 5 g fish oil/day for six weeks. Plasma TG concentrations were measured before and after the supplementation. Based on the initial GRS of 31 SNPs (GRS31), we computed three new GRSs by adding new SNPs identified in the UK Biobank: GRS32 (rs55707100), GRS38 (seven new SNPs specifically associated with plasma TG levels), and GRS46 (all 15 new SNPs associated with plasma lipid levels). The initial GRS31 explained 50.1% of the variance in plasma TG levels during the intervention, whereas GRS32, GRS38, and GRS46 explained 49.1%, 45.9%, and 45%, respectively. A significant impact on the probability of being classified as a responder or a nonresponder was found for each of the GRSs analyzed, but none of them outperformed the predictive capacity of GRS31 in any of the metrics analyzed, i.e., accuracy, area under the response operating curve (AUC-ROC), sensitivity, specificity and McFadden's pseudo R2. The addition of SNPs identified in the UK Biobank to the initial GRS31 did not significantly improve its capacity to predict the plasma TG response to an n-3 FA supplementation. Thus, GRS31 still remains the most precise tool so far by which to discriminate the individual responsiveness to n-3 FAs. Further studies are needed in the field to increase our knowledge of factors underlying the heterogeneity observed in the metabolic response to an n-3 FA supplementation. [ABSTRACT FROM AUTHOR]

We compared endogenous ω-3 PUFA production to supplementation for improving obesity-related metabolic dysfunction. Fat-1 transgenic mice, who endogenously convert exogenous ω-6 to ω-3 PUFA, and wild-type littermates were fed a high-fat diet and a daily dose of either ω-3 or ω-6 PUFA-rich oil for 12 wk. The endogenous ω-3 PUFA production improved glucose intolerance and insulin resistance but not hepatic steatosis. Conversely, ω-3 PUFA supplementation fully prevented hepatic steatosis but failed to improve insulin resistance. Both models increased hepatic levels of ω-3 PUFA-containing 2-monoacylglycerol and N-acylethanolamine congeners, and reduced levels of ω-6 PUFA-derived endocannabinoids with ω-3 PUFA supplementation being more efficacious. Reduced hepatic lipid accumulation associated with the endocannabinoidome metabolites EPEA and DHEA, which was causally demonstrated by lower lipid accumulation in oleic acid-treated hepatic cells treated with these metabolites. While both models induced a significant fecal enrichment of the beneficial Allobaculum genus, mice supplemented with ω-3 PUFA displayed additional changes in the gut microbiota functions with a significant reduction of fecal levels of the proinflammatory molecules lipopolysaccharide and flagellin. Multiple-factor analysis identify that the metabolic improvements induced by ω-3 PUFAs were accompanied by a reduced production of the proinflammatory cytokine TNFα, and that ω-3 PUFA supplementation had a stronger effect on improving the hepatic fatty acid profile than endogenous ω-3 PUFA. While endogenous ω-3 PUFA production preferably improves glucose tolerance and insulin resistance, ω-3 PUFA intake appears to be required to elicit selective changes in hepatic endocannabinoidome signaling that are essential to alleviate high-fat diet-induced hepatic steatosis. [ABSTRACT FROM AUTHOR]