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Four multi-catheterized lactating goats were used in a 4 × 4 Latin square experiment to investigate the responses of amino acid metabolism in portal-drained viscera (PDV), liver, and mammary glands to short-term varying supplies of methionine (Met). During the last 45 h in each experimental period, goats were fasted for 12 h and then abomasally infused with an amino acid (AA) mixture plus glucose for 33 h. Treatments consisted of graded removal of Met from an infused AA mixture to achieve Met content in the infusate of 100% (complete), 60%, 30%, or 0% that in casein. Graded Met removal decreased the production of milk, milk protein, lactose, and fat linearly whilst also decreasing arterial Met concentration linearly (P 0.1) was maintained as Met supply declined. This was achieved through increased mammary affinity (P

Stress granules (SGs) are dynamic cytoplasmic protein-RNA structures that form in response to various stress conditions, including viral infection. Porcine epidemic diarrhea virus (PEDV) variant-related diarrhea has caused devastating economic losses to the swine industry worldwide. In this study, we found that the percentage of PEDV-infected cells containing SGs is nearly 20%; meanwhile, PEDV-infected cells were resistant to sodium arsenite (SA)-induced SGs formation, as demonstrated by the recruitment of SGs marker proteins, including G3BP1 and TIA1. Moreover, the formation of SGs induced by SA treatment was suppressed by PEDV papain-like protease confirmed by confocal microscopy. Further study showed that PEDV infection disrupted SGs formation by downregulating G3BP1 expression. Additionally, PEDV replication was significantly enhanced when SGs' assembly was impaired by silencing G3BP1. Taken together, our findings attempt to illuminate the specific interaction mechanism between SGs and PEDV, which will help us to elucidate the pathogenesis of PEDV infection in the near future.

Abstract The MEN1 gene, which encodes the protein Menin, was investigated for its regulatory role in milk protein synthesis in mammary glands. Menin responds to nutrient and hormone levels via the PI3K/Akt/mTOR pathway. Bovine mammary epithelial cells and tissues were used as experimental models in this study. The results revealed that the milk protein synthesis capacity of mammary epithelial cells could be regulated by MEN1/Menin. The overexpression of Menin caused significant suppression of factors involved in the mTOR pathway, as well as milk protein κ-casein (CSNK). In contrast, a significant increase in these factors and CSNK was observed upon MEN1/Menin knockdown. The repression of MEN1/Menin on the mTOR pathway was also observed in mammary gland tissues. Additionally, MEN1/Menin was found to elicit a negative response on prolactin (PRL) and/or insulin (INS), which caused a similar downstream impact on mTOR pathway factors and milk proteins. Collectively, our data indicate that MEN1/Menin could play a regulatory role in milk protein synthesis through mTOR signaling in the mammary gland by mediating the effects of hormones and nutrient status. The discovery of Menin’s role in mammary glands suggests Menin could be potential new target for the improvement of milk performance and adjustment of lactation period of dairy cows.

To evaluate mucosal immunity of normal and immunosuppressed chickens vaccinated with live Newcastle disease (ND) vaccine, cyclophosphamide (CY) was used to generate immunosuppressed chickens. Normal and immunosuppressed chickens were vaccinated with the Lasota ND vaccine by ocular-nasal route at three weeks of age and challenged with virulent ND virus (vNDV) at day 28 post-vaccination (pv). The immunosuppressed chickens had significantly lower relative weight of the bursa of Fabricius and serum antibody HI titers compared to CY-untreated chickens. Compared with normal chickens, significant lower levels of IgA antibodies were detected in tracheal washings, duodenal washings and bile of immunosuppressed chickens in the whole experimental period. Immuno-histochemical experiment also showed that small numbers of IgA positive cells were found in intestinal tissues of immunosuppressed chickens at day 28 pv. There was only a partial protective effect on immunosuppressed chickens post challenge with virulent ND virus (vNDV). These findings increase our understanding of the protective mucosal immune response against ND vaccine and suggest that mucosal immunity play an important role against NDV infection.

The objectives of the present study were to characterize the chemical composition, antioxidant activity and hepatoprotective effect of the polysaccharides from Taishan Pinus massoniana pollen (TPPPS). HPLC analysis showed that TPPPS was an acidic heteropolysaccharide with glucose and arabinose as the main component monosaccharides (79.6%, molar percentage). Fourier transform-infrared spectroscopy (FT-IR) analysis indicated that the spectra of TPPPS displayed infrared absorption peaks characteristic of polysaccharides. In in vitro assays TPPPS exhibited different degrees of dose-dependent antioxidant activities , and this was further verified by suppression of CCl4-induced oxidative stress in the liver with three tested doses of TPPPS (100, 200, and 400 mg/kg bw) in rats. Pretreatment with TPPPS significantly decreased the levels of alanine aminotransferase (AST), aspartate aminotransferase (ALT), alkaline phosphatase (ALP), lactic dehydrogenase (LDH) and malondialdehyde (MDA) against CCl4 injuries, and elevated the activities of superoxide dismutase (SOD) as well as glutathione peroxidase (GSH-Px). Histopathological observation further confirmed that TPPPS could protect the liver tissues from CCl4-induced histological alternation. These results suggest that TPPPS has strong antioxidant activities and significant protective effect against acute hepatotoxicity induced by CCl4. The hepatoprotective effect may partly be related to its free radical scavenging effect, increasing antioxidant activity and inhibiting lipid peroxidation.

BACKGROUND: Lactogenesis includes two stages. Stage I begins a few weeks before parturition. Stage II is initiated around the time of parturition and extends for several days afterwards. METHODOLOGY/PRINCIPAL FINDINGS: To better understand the molecular events underlying these changes, genome-wide gene expression profiling was conducted using digital gene expression (DGE) on bovine mammary tissue at three time points (on approximately day 35 before parturition (-35 d), day 7 before parturition (-7 d) and day 3 after parturition (+3 d)). Approximately 6.2 million (M), 5.8 million (M) and 6.1 million (M) 21-nt cDNA tags were sequenced in the three cDNA libraries (-35 d, -7 d and +3 d), respectively. After aligning to the reference sequences, the three cDNA libraries included 8,662, 8,363 and 8,359 genes, respectively. With a fold change cutoff criteria of ≥ 2 or ≤-2 and a false discovery rate (FDR) of ≤ 0.001, a total of 812 genes were significantly differentially expressed at -7 d compared with -35 d (stage I). Gene ontology analysis showed that those significantly differentially expressed genes were mainly associated with cell cycle, lipid metabolism, immune response and biological adhesion. A total of 1,189 genes were significantly differentially expressed at +3 d compared with -7 d (stage II), and these genes were mainly associated with the immune response and cell cycle. Moreover, there were 1,672 genes significantly differentially expressed at +3 d compared with -35 d. Gene ontology analysis showed that the main differentially expressed genes were those associated with metabolic processes. CONCLUSIONS: The results suggest that the mammary gland begins to lactate not only by a gain of function but also by a broad suppression of function to effectively push most of the cell's resources towards lactation.

BackgroundA large and growing body of neuroimaging research has concentrated on patients with attention-deficit/hyperactivity disorder (ADHD), but with inconsistent conclusions. This article was intended to investigate the common and certain neural alterations in the structure and function of the brain in patients with ADHD and further explore the differences in brain alterations between adults and children with ADHD.MethodsWe conducted an extensive literature search of whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies associated with ADHD. Two separate meta-analyses with the seed-based d mapping software package for functional neural activation and gray matter volume (GMV) were carried out, followed by a joint analysis and a subgroup analysis.ResultsThis analysis included 29 VBM studies and 36 fMRI studies. Structurally, VBM analysis showed that the largest GMV diminutions in patients with ADHD were in several frontal-parietal brain regions, the limbic system, and the corpus callosum. Functionally, fMRI analysis discovered significant hypoactivation in several frontal-temporal brain regions, the right postcentral gyrus, the left insula, and the corpus callosum.ConclusionThis study showed that abnormal alterations in the structure and function of the left superior frontal gyrus and the corpus callosum may be the key brain regions involved in the pathogenesis of ADHD in patients and may be employed as an imaging metric for patients with ADHD pending future research. In addition, this meta-analysis discovered neuroanatomical or functional abnormalities in other brain regions in patients with ADHD as well as findings that can be utilized to guide future research.

Accumulating evidence suggested that overweight and smoking often co-exist. However, current neuroimaging researches have almost always studied smoking or overweight status separately. Here we sought to investigate the neurobiological mechanisms of this comorbid association, by detecting spontaneous brain activity changes associated with smoking and weight status separately and collectively. We used 2 × 2 factorial design and included the following four groups: overweight/normal-weight smokers (n = 34/n = 30) and overweight/normal-weight non-smokers (n = 22/n = 24). The spontaneous brain activity among the four groups was comparable using an amplitude of low-frequency fluctuation (ALFF) method based on resting-state fMRI (rs-fMRI). Furthermore, correlation analyses between brain activity changes, smoking severity and BMI values were performed. A main effect of smoking was discovered in the default mode network (DMN) and visual network related brain regions. Moreover, overweight people had high ALFF value in the brain regions associated with reward and executive control. More importantly, smoking and overweight both affected brain activity of the middle temporal gyrus (MTG), but the effect was opposite. And the brain activity of MTG was negatively correlated with smoking years, pack year and BMI value. These results suggest that smoking and overweight not only affect spontaneous brain activity alone, but also paradoxically affect spontaneous brain activity in the MTG. This suggests that we need to control for weight as a variable when studying spontaneous brain activity in smokers. Besides, this interaction may provide a neurological explanation for the comorbidity of overweight and smoking and a target for the treatment of comorbid populations.

BackgroundMany neuroimaging studies have reported abnormalities in brain structure and function in internet gaming disorder (IGD). However, the findings were divergent. We aimed to provide evidence-based evidence of structural and functional changes in IGD by conducting a meta-analysis integrating these studies quantitatively.MethodA systematic search was conducted in PubMed, ScienceDirect, Web of Science, and Scopus from January 1, 2010 to October 31, 2021, to identify eligible voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies. Brain alternations between IGD subjects and healthy controls (HCs) were compared using the anisotropic seed-based d mapping (AES-SDM) meta-analytic method. Meta-regression analysis was used to investigate the relationship between gray matter volume (GMV) alterations and addiction-related clinical features.ResultsThe meta-analysis contained 15 VBM studies (422 IGD patients and 354 HCs) and 30 task-state fMRI studies (617 IGD patients and 550 HCs). Compared with HCs, IGD subjects showed: (1) reduced GMV in the bilateral anterior/median cingulate cortex, superior/inferior frontal gyrus and supplementary motor area; (2) hyperactivation in the bilateral inferior frontal gyrus, precentral gyrus, left precuneus, right inferior temporal gyrus and right fusiform; (3) hypoactivation in the bilateral lingual and the left middle frontal gyrus; and (4) both decreased GMV and increased activation in the left anterior cingulate. Furthermore, Meta-regression revealed that GMV reduction in left anterior cingulate were positively correlated with BIS-11 score [r = 0.725, p = 0.012(uncorrected)] and IAT score [r = 0.761, p = 0.017(uncorrected)].ConclusionThis meta-analysis showed structural and functional impairments in brain regions related to executive control, cognitive function and reward-based decision making in IGD. Furthermore, multi-domain assessments captured different aspects of neuronal changes in IGD, which may help develop effective interventions as potential therapeutic targets.

BackgroundPrevious voxel-based morphometric (VBM) and functional magnetic resonance imaging (fMRI) studies have shown changes in brain structure and function in cocaine addiction (CD) patients compared to healthy controls (HC). However, the results of these studies are poorly reproducible, and it is unclear whether there are common and specific neuroimaging changes. This meta-analysis study aimed to identify structural, functional, and multimodal abnormalities in CD patients.MethodsThe PubMed database was searched for VBM and task-state fMRI studies performed in CD patients between January 1, 2010, and December 31, 2021, using the SEED-BASE d MAP software package to perform two independent meta-groups of functional neural activation and gray matter volume, respectively. Analysis, followed by multimodal analysis to uncover structural, functional, and multimodal abnormalities between CD and HC.ResultsThe meta-analysis included 14 CD fMRI studies (400 CD patients and 387 HCs) and 11 CD VBM studies (368 CD patients and 387 controls). Structurally, VBM analysis revealed significantly lower gray matter volumes in the right superior temporal gyrus, right insula, and right retrocentral gyrus than in the HC. On the other hand, the right inferior parietal gyrus increased in gray matter (GM) volume in CD patients. Functionally, fMRI analysis revealed activation in the right temporal pole, right insula, and right parahippocampal gyrus. In the right inferior parietal gyrus, the left inferior parietal gyrus, the left middle occipital gyrus, and the right middle frontal gyrus, the degree of activation was lower.ConclusionThis meta-analysis showed that CD patients had significant brain GM and neural changes compared with normal controls. Furthermore, multi-domain assessments capture different aspects of neuronal alterations in CD, which may help develop effective interventions for specific functions.

BackgroundTobacco smoking and being overweight could lead to adverse health effects, which remain an important public health problem worldwide. Research indicates that overlapping pathophysiology may contribute to tobacco addiction and being overweight, but the neurobiological interaction mechanism between the two factors is still unclear.MethodsThe current study used a mixed sample design, including the following four groups: (i) overweight long-term smokers (n = 24); (ii) normal-weight smokers (n = 28); (iii) overweight non-smokers (n = 19), and (iv) normal-weight non-smokers (n = 28), for a total of 89 male subjects. All subjects underwent resting-state functional magnetic resonance imaging (rs-fMRI). Regional homogeneity (ReHo) was used to compare internal cerebral activity among the four groups. Interaction effects between tobacco addiction and weight status on ReHo were detected using a two-way analysis of variance, correcting for age, years of education, and head motion.ResultsA significant interaction effect between tobacco addiction and weight status is shown in right superior frontal gyrus. Correlation analyses show that the strengthened ReHo value in the right superior frontal gyrus is positively associated with pack-year. Besides, the main effect of tobacco addiction is specially observed in the occipital lobe and cerebellum posterior lobe. As for the main effect of weight status, the right lentiform nucleus, left postcentral gyrus, and brain regions involved in default mode network (DMN) survived.ConclusionsThese results shed light on an antagonistic interaction on brain ReHo between tobacco addiction and weight status in the right superior frontal gyrus, which may be a clinical neuro-marker of comorbid tobacco addiction and overweight. Our findings may provide a potential target to develop effective treatments for the unique population of comorbid tobacco addiction and overweight people.

Previous studies have implicated abnormal functional coordination in brain regions of smokers. Neuroimaging studies demonstrated alternations in brain connectivity by using the resting-state functional connectivity (rsFC) method which arbitrarily chooses specific networks or seed regions as priori selections and cannot provide a full picture of the FC changes in chronic smokers. The aim of this study was to investigate the whole-brain functional coordination measured by functional connectivity density (FCD). As the variance of brain activity, dynamic FCD (dFCD) was performed to investigate dynamic changes of whole-brain integration in chronic smokers. In total, 120 chronic smokers and 56 nonsmokers were recruited, and static FCD and dFCD were performed to investigate aberrance of whole-brain functional coordination. Shared aberrance in visual areas has been found in both static and dFCD study in chronic smokers. Furthermore, the results exhibited that both heavy and light smokers demonstrated decreased dFCD in the visual cortex and left precuneus, and also increased dFCD in the right orbitofrontal cortex, left caudate, right putamen, and left thalamus compared with nonsmokers. In addition, alternations of dFCD have been found between heavy and light smokers. Furthermore, the dFCD variations showed significant positive correlation with smoking-related behaviors. The results demonstrated that chronic smokers not only have some initial areas, but also have some regions associated with severity of cigarette smoking. Lastly, dFCD could provide more subtle variations in chronic smokers, and the combination of static and dFCD may deepen our understanding of the brain alternations in chronic smokers.

Background: Major depressive disorder (MDD) has demonstrated abnormalities of static intrinsic brain activity measured by amplitude of low-frequency fluctuation (ALFF). Recent studies regarding the resting-state functional magnetic resonance imaging (rs-fMRI) have found the brain activity is inherently dynamic over time. Little is known, however, regarding the temporal dynamics of local neural activity in MDD. Here, we investigated whether temporal dynamic changes in spontaneous neural activity are influenced by MDD.Methods: We recruited 81 first-episode, drug-naive MDD patients and 64 age-, gender-, and education-matched healthy controls who underwent rs-fMRI. A sliding-window approach was then adopted for the estimation of dynamic ALFF (dALFF), which was used to measure time-varying brain activity and then compared between the two groups. The relationship between altered dALFF variability and clinical variables in MDD patients was also analyzed.Results: MDD patients showed increased temporal variability (dALFF) mainly focused on the bilateral thalamus, the bilateral superior frontal gyrus, the right middle frontal gyrus, the bilateral cerebellum posterior lobe, and the vermis. Furthermore, increased dALFF variability values in the right thalamus and right cerebellum posterior lobe were positively correlated with MDD symptom severity.Conclusions: The overall results suggest that altered temporal variability in corticocerebellar–thalamic–cortical circuit (CCTCC), involved in emotional, executive, and cognitive, is associated with drug-naive, first-episode MDD patients. Moreover, our study highlights the vital role of abnormal dynamic brain activity in the cerebellar hemisphere associated with CCTCC in MDD patients. These findings may provide novel insights into the pathophysiological mechanisms of MDD.

Background: The findings of many neuroimaging studies in patients with first-episode major depressive disorder (MDD), and even those of previous meta-analysis, are divergent. To quantitatively integrate these studies, we performed a meta-analysis of gray matter volumes using voxel-based morphometry (VBM).Methods: We performed a comprehensive literature search for relevant studies and traced the references up to May 1, 2021 to select the VBM studies between first-episode MDD and healthy controls (HC). A quantitative meta-analysis of VBM studies on first-episode MDD was performed using the Seed-based d Mapping with Permutation of Subject Images (SDM-PSI) method, which allows a familywise error rate (FWE) correction for multiple comparisons of the results. Meta-regression was used to explore the effects of demographics and clinical characteristics.Results: Nineteen studies, with 22 datasets comprising 619 first-episode MDD and 707 HC, were included. The pooled and subgroup meta-analysis showed robust gray matter reductions in the left insula, the bilateral parahippocampal gyrus extending into the bilateral hippocampus, the right gyrus rectus extending into the right striatum, the right superior frontal gyrus (dorsolateral part), the left superior frontal gyrus (medial part) and the left superior parietal gyrus. Meta-regression analyses showed that higher HDRS scores were significantly more likely to present reduced gray matter volumes in the right amygdala, and the mean age of MDD patients in each study was negatively correlated with reduced gray matter in the left insula.Conclusions: The present meta-analysis revealed that structural abnormalities in the fronto-striatal-limbic and fronto-parietal networks are essential characteristics in first-episode MDD patients, which may become a potential target for clinical intervention.

Background: Patients with Internet gaming disorder (IGD) and attention-deficit/hyperactivity disorder (ADHD) have high comorbidity but it is still unknown whether these disorders have shared and distinctive neuroimage alterations.Objective: The aim of this meta-analysis was to identify shared and disorder-specific structural, functional, and multimodal abnormalities between IGD and ADHD.Methods: A systematic literature search was conducted for whole-brain voxel-based morphometry (VBM) and functional magnetic resonance imaging (fMRI) studies comparing people with IGD or ADHD with healthy controls. Regional gray matter volume (GMV) and fMRI differences were compared over the patient groups and then a quantitative comparison was performed to find abnormalities (relative to controls) between IGD and ADHD using seed-based d mapping meta-analytic methods.Result: The meta-analysis contained 14 IGD VBM studies (contrasts covering 333 IGDs and 335 HCs), 26 ADHD VBM studies (1,051 patients with ADHD and 887 controls), 30 IGD fMRI studies (603 patients with IGD and 564 controls), and 29 ADHD fMRI studies (878 patients with ADHD and 803 controls). Structurally, VBM analysis showed disorder-specific GMV abnormality in the putamen among IGD subjects and orbitofrontal cortex in ADHD and shared GMV in the prefrontal cortex. Functionally, fMRI analysis discovered that IGD-differentiating increased activation in the precuneus and shared abnormal activation in anterior cingulate cortex, insular, and striatum.Conclusion: IGD and ADHD have shared and special structural and functional alterations. IGD has disorder-differentiating structural alterations in the putamen and ADHD has alterations in the orbitofrontal cortex. Disorder-differentiating fMRI activations were predominantly observed in the precuneus among IGD subjects and shared impairing function connection was in the rewards circuit (including ACC, OFC, and striatum).