Study on the effects of toosendanin against Eimeria tenella and its impact on the apoptosis of cecal cells in chicks.

To investigate the therapeutic effect of toosendanin (TSN) against Eimeria tenella (E. tenella) in chicks. In this experiment, a chick model of artificially induced E. tenella infection was established. The anti-coccidial effect was investigated by treating different doses of TSN. A preliminary mechanism of action was conducted, using cecal cell apoptosis as a starting point. TSN at the concentration of 5 mg/kg BW showed the best effect against E. tenella with the ACI value of 164.35. In addition, TSN reduced pathological damage to cecal tissue, increased the secretion of glycogen and mucus in cecal mucosa, and enhanced the mucosal protective effect. It also elevated the levels of IFN-γ, IL-2, and IgG in serum, and raised the sIgA content in cecal tissue of infected chicks, thereby improving overall immune function. TSN was observed to promote the apoptosis of cecum tissue cells by TUNEL staining analysis. Immunohistochemistry analysis revealed that in TSN-treated groups, the expression of Caspase-3 and Bax was elevated, while the expression of Bcl-2 was reduced. TSN induced apoptosis in host cells by dose-dependently decreasing the Bcl-2/Bax ratio and upregulating Caspase-3 expression. In summary, TSN exhibited significant anticoccidial efficacy by facilitating apoptosis in host cecal cells, with the most pronounced effect observed at a dosage of 5 mg/kg body weight.

Selenium maintains intestinal epithelial cells to activate M2 macrophages against deoxynivalenol injury.

Selenium (Se) is indispensable in alleviating various types of intestinal injuries. Here, we thoroughly investigated the protective effect of Se on the regulation of the epithelial cell-M2 macrophages pathway in deoxynivalenol (DON)-induced intestinal damage. In the present study, Se has positive impacts on gut health by improving gut barrier function and reducing the levels of serum DON in vivo. Furthermore, our study revealed that Se supplementation increased the abundances of GPX4, p-PI3K, and AKT, decreased the levels of 4-HNE and inhibited ferroptosis. Moreover, when mice were treated with DON and Fer-1(ferroptosis inhibitor), ferroptosis was suppressed and PI3K/AKT pathway was activated. These results indicated that GPX4-PI3K/AKT-ferroptosis was a predominant pathway in DON-induced intestinal inflammation. Interestingly, we discovered that both the number of M2 anti-inflammatory macrophages and the levels of CSF-1 decreased while the pro-inflammatory cytokine IL-6 increased in the intestine and MODE-K cells supernatant. Therefore, Se supplementation activated the CSF-1-M2 macrophages axis, resulting in a decrease in IL-6 expression and an enhancement of the intestinal anti-inflammatory capacity. This study provides novel insights into how intestinal epithelial cells regulate the CSF-1-M2 macrophage pathway, which is essential in maintaining intestinal homeostasis confer to environmental hazardous stimuli.

18Beta-Glycyrrhetinic Acid Attenuates H2O2-Induced Oxidative Damage and Apoptosis in Intestinal Epithelial Cells via Activating the PI3K/Akt Signaling Pathway.

Oxidative stress causes gut dysfunction and is a contributing factor in several intestinal disorders. Intestinal epithelial cell survival is essential for maintaining human and animal health under oxidative stress. 18beta-Glycyrrhetinic acid (GA) is known to have multiple beneficial effects, including antioxidant activity; however, the underlying molecular mechanisms have not been well established. Thus, the present study evaluated the therapeutic effects of GA on H2O2-induced oxidative stress in intestinal porcine epithelial cells. The results showed that pretreatment with GA (100 nM for 16 h) significantly increased the levels of several antioxidant enzymes and reduced corresponding intracellular levels of reactive oxidative species and malondialdehyde. GA inhibited cell apoptosis via activating the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway, as confirmed by RNA sequencing. Further analyses demonstrated that GA upregulated the phosphorylation levels of PI3K and Akt and the protein level of B cell lymphoma 2, whereas it downregulated Cytochrome c and tumor suppressor protein p53 levels. Moreover, molecular docking analysis predicted the binding of GA to Vasoactive intestinal peptide receptor 1, a primary membrane receptor, to activate the PI3K/Akt signaling pathway. Collectively, these results revealed that GA protected against H2O2-induced oxidative damage and cell apoptosis via activating the PI3K/Akt signaling pathway, suggesting the potential therapeutic use of GA to alleviate oxidative stress in humans/animals.

Expanding the Hydrophobic Cavity Surface of Azocalix[4]arene to Enable Biotin/Avidin Affinity with Controlled Release.

The development of artificial receptors that combine ultrahigh-affinity binding and controllable release for active guests holds significant importance in biomedical applications. On one hand, a complex with an exceedingly high binding affinity can resist unwanted dissociation induced by dilution effect and complex interferents within physiological environments. On the other hand, stimulus-responsive release of the guest is essential for precisely activating its function. In this context, we expanded hydrophobic cavity surface of a hypoxia-responsive azocalix[4]arene, affording Naph-SAC4A. This modification significantly enhanced its aqueous binding affinity to 1013 M-1, akin to the naturally occurring strongest recognition pair, biotin/(strept-)avidin. Consequently, Naph-SAC4A emerges as the first artificial receptor to simultaneously integrate ultrahigh recognition affinity and actively controllable release. The markedly enhanced affinity not only improved Naph-SAC4A's sensitivity in detecting rocuronium bromide in serum, but also refined the precision of hypoxia-responsive doxorubicin delivery at the cellular level, demonstrating its immense potential for diverse practical applications.

Contributions of Cerebral White Matter Hyperintensities to Postural Instability in Aging with and without Alcohol Use Disorder.

BACKGROUND: Postural instability and brain white matter hyperintensities (WMH) are both noted markers of normal aging and alcohol use disorder (AUD). Here, we questioned what variables contribute to sway path/WMH relations in individuals with AUD and healthy control participants. METHOD: The data comprised 404 balance platform sessions, yielding sway path length and MRI acquired cross-sectionally or longitudinally, in 102 control and 158 AUD participants, ages 25-80 years. Balance sessions were typically conducted on the same day as MRI FLAIR acquisitions, permitting WMH volume quantification. Factors considered in multiple regression analyses as potential contributors to relations between WMH volumes and postural instability were age, sex, socioeconomic status, education, pedal 2-point discrimination, systolic and diastolic blood pressure, body mass index, depressive symptoms, total alcohol consumed in the past year, and race. RESULTS: Initial analysis identified diagnosis, age, sex, and race as significant contributors to observed sway path/WMH relations. Inclusion of these factors as predictors in multiple regression analysis substantially attenuated the sway/WMH relations in both AUD and healthy control groups. Women, irrespective of diagnosis or race, had shorter sway paths than men. Black participants, irrespective of diagnosis or sex, had shorter sway paths than non-Black participants despite having modestly larger WMH volumes than non-Black participants, possibly a reflection of the younger age of the Black sample. DISCUSSION: Longer sway paths were related to larger WMH volumes in healthy men and women, with and without AUD. Critically, however, age nearly fully accounted for these relations.

Enantiopure Corral[4]BINOLs as Ultrastrong Receptors for Recognition and Differential Sensing of Steroids.

The precise recognition and sensing of steroids, a type of vital biomolecules, hold immense practical value across various domains. In this study, we introduced corral[4]BINOLs (C[4]BINOLs), a pair of enantiomeric conjugated deep-cavity hosts, as novel synthetic receptors for binding steroids. Due to the strong hydrophobic effect of their deep nonpolar, chiral cavities, the two enantiomers of C[4]BINOLs demonstrated exceptionally high recognition affinities (up to 1012 M-1) for 16 important steroidal compounds as well as good enantioselectiviy (up to 15.5) in aqueous solutions, establishing them as the most potent known steroid receptors. Harnessing their ultrahigh affinity, remarkable enantioselectivity, and fluorescence emission properties, the two C[4]BINOL enantiomers were employed to compose a fluorescent sensor array which achieved discrimination and sensing of 16 structurally similar steroids at low concentrations.

Identification of Characteristic Bioactive Compounds in Silkie Chickens, Their Effects on Meat Quality, and Their Gene Regulatory Network.

Silkie chicken, an important chicken breed with high medicinal and nutritional value, has a long history of being used as a dietary supplement in China. However, the compounds with health-promoting effects in Silkie chickens remain unclear. In the present study, we conducted a comprehensive analysis of metabolic and lipidomic profiles to identify the characteristic bioactive compounds in Silkie chickens, using a common chicken breed as control. The results showed that the levels of 13 metabolites including estradiol, four lipid subclasses including cardiolipin (CL), eight lipid molecules, and three fatty acids including docosahexaenoic acid (C22:6) were significantly increased in Silkie chickens, which have physiological activities such as resisting chronic diseases and improving cognition. These characteristic bioactive compounds have effects on meat quality characteristics, including improving its water-holding capacity and umami taste and increasing the content of aromatic compounds and phenols. The differentially expressed genes (DEGs) between the two chicken breeds revealed the regulatory network for these characteristic bioactive compounds. Fifteen DEGs, including HSD17B1, are involved in the synthesis of characteristic metabolites. Eleven DEGs, including ELOVL2, were involved in the synthesis and transport of characteristic lipids and fatty acids. In summary, we identified characteristic bioactive compounds in Silkie chickens, and analyzed their effects on meat quality characteristics. This study provided important insight into Silkie chicken meat as a functional food.

Contributions of cerebral white matter hyperintensities, age, and pedal perception to postural sway in people living with HIV.

OBJECTIVE: With aging, people living with HIV (PLWH) have diminishing postural stability that increases liability for falls. Factors and neuromechanisms contributing to instability are incompletely known. Brain white matter abnormalities seen as hyperintense (WMH) signals have been considered to underlie instability in normal aging and PLWH. We questioned whether sway-WMH relations endured after accounting for potentially relevant demographic, physiological, and HIV-related variables. DESIGN: Mixed cross-sectional/longitudinal data acquired over 15 years in 141 PLWH and 102 age-range matched controls, 25-80 years old. METHODS: Multimodal structural MRI data were quantified for 7 total and regional WMH volumes. Static posturography acquired with a force platform measured sway path length separately with eyes closed and eyes open. Statistical analyses used multiple regression with mixed modeling to test contributions from non-MRI and non-path data on sway path-WMH relations. RESULTS: In simple correlations, longer sway paths were associated with larger WMH volumes in PWLH and controls. When demographic, physiological, and HIV-related variables were entered into multiple regressions, the sway-WMH relations under both vision conditions in the controls were attenuated when accounting for age and 2-point pedal discrimination. Although the sway-WMH relations in PLWH were influenced by age, 2-point pedal discrimination, and years with HIV infection, the sway-WMH relations endured for 5 of the 7 regions in the eyes-open condition. CONCLUSIONS: The constellation of age-related increasing instability while standing, degradation of brain white matter integrity, and peripheral pedal neuropathy is indicative of advancing fraility and liability for falls as people age with HIV infection.

Anthelmintic efficacy of nitazoxanide in dogs naturally infected with Toxocara canis.

Toxocara canis (T. canis) is a gastrointestinal nematode in dogs, and its larvae also infect humans, causing severe larval migratory disease. Anthelmintic drugs have become the primary means to combat T. canis. In this study, the efficacy of nitazoxanide (NTZ) was tested against all the internal stages of T. canis, including L3 larval stage in vitro experiments and gastrointestinal worm in vivo experiments. In the in vitro experiment, after treatment with NTZ at 7.81 and 62.5 µg/mL for 12 h, the larval mortality efficacy reached 90.0 and 100.0%, respectively. In the in vivo experiments, 100 mg/kg NTZ possessed good anthelmintic efficacy against T. canis, with an egg per gram (EPG) reduction of 99.19%, and 90.00% of dogs cleared with residual worms. These results were comparable to those of the positive control drug. The highest anthelmintic efficacy was observed in the group treated with 150 mg/kg NTZ. Based on faecal egg counts, the number of T. canis eggs decreased by 100.00%, and the percentage of dogs cleared with residual worms achieved 90.00% after 7 days of treatment in the 150-mg/kg NTZ treatment group. In general, NTZ showed great potential to be applied as an anthelmintic against T. canis.

Deposition and enrichment of carotenoids in livestock products: An overview.

A wide range of research has illustrated that carotenoids play a key role in human health through their versatile beneficial biological functions. Traditionally, the majority dietary sources of carotenoids for humans are obtained from vegetables and fruits, however, the contribution of animal-derived foods has attracted more interest in recent years. Livestock products such as eggs, meat, and milk have been considered as the appropriate and unique carriers for the deposition of carotenoids. In addition, with the enrichment of carotenoids, the nutritional quality of these animal-origin foods would be improved as well as the economic value. Here, we offer an overview covering aspects including the physicochemical properties of carotenoids, the situation of carotenoids fortified in livestock products, and the pathways that lead to the deposition of carotenoids in livestock products. The summary of these important nutrients in livestock products will provide references for animal husbandry and human health.

Development of NHAcGD2/NHAcGD3 conjugates of bacteriophage MX1 virus-like particles as anticancer vaccines.

The successful development of an anticancer vaccine will be a giant leap forward in cancer prevention and treatment. Herein, the bacteriophage MX1 coat protein virus-like particles (MX1 VLPs) have been conjugated with 9NHAc-GD2 (NHAcGD2) to obtain a MX1-NHAcGD2 conjugate. Intriguingly, vaccinating against this conjugate produced a robust anti-NHAcGD2 IgG response in mice, with an average IgG titer of over 3 million. More interestingly, antibodies induced by the MX1-NHAcGD2 conjugate bound well to IMR-32 neuroblastoma cells and had potent complement-dependent cytotoxic (CDC) effects on IMR-32 cells. Inspired by the superiority of the 9NHAc-GD2 antigen, we also designed another 9NHAc-modified ganglioside antigen, 9NHAc-GD3 (NHAcGD3), to overcome the hydrolytic instability of 9-O-acetylated-GD3. By coupling NHAcGD3 with MX1 VLP, the MX1-NHAcGD3 conjugate was constructed. Strikingly, vaccination of MX1-NHAcGD3 elicited high anti-NHAcGD3 IgG antibodies, which effectively recognized human malignant melanoma SK-MEL-28 cells and had a significant CDC effect against this cell line. This study provides novel MX1-NHAcGD2 and MX1-NHAcGD3 conjugates with broad clinical translational prospects as promising anticancer vaccines.

Ponazuril: Clinical efficacy, ultrastructure, and histopathology studies of in vivo anticoccidial action against Eimeria tenella.

Ponazuril, a novel antiprotozoal drug in the class of triazine, has shown a promising application on apicomplexan infections in poultry and livestock. However, the effect and mechanism of action of ponazuril against Eimeria tenella (E. tenella) are unclear. The efficacy against E. tenella was initially studied by administering different doses of ponazuril in drinking water. The treated stage and site of ponazuril on E. tenella were observed through ultrastructural and histopathological analyses. Chicks were orally treated with a dose of 15 mg/kg body weight of ponazuril at different endogenous stages of E. tenella post-infection. According to the clinical study, the values of anticoccidial indices (ACI) were 157.0, 162.3, 196.9, 194.5, and 190.9, respectively, when the ponazuril was administered in drinking water at doses of 5, 10, 20, 40, and 50 mg/L for two consecutive days after infection. Among them, the 20 mg/L ponazuril group showed the best anticoccidial effect, which was superior to that of the toltrazuril treatment group, with an ACI value of 191.7. Histological analysis indicated that ponazuril effectively relieved cecal lesions, and decreased the number of merozoites. Transmission electron micrographs (TEM) observed that merozoites became irregular in shape, and some apparent protrusions of the outer membrane were presented especially the second-generation merozoites. Additionally, abnormalities in the development of WFBI and WFBII in the macrogametocyte were observed, which may affect the formation of the ovule wall. Moreover, merozoites in the treated group showed uneven and marginalized chromatin and mitochondrial swelling. These results suggested ponazuril is a potential anticoccidial drug, providing information on the mechanism of anticoccidial effects.

Age-Accelerated Increase of White Matter Hyperintensity Volumes Is Exacerbated by Heavy Alcohol Use in People Living With HIV.

BACKGROUND: Antiretroviral treatment has enabled people living with HIV infection to have a near-normal life span. With longevity comes opportunities for engaging in risky behavior, including initiation of excessive drinking. Given that both HIV infection and alcohol use disorder (AUD) can disrupt brain white matter integrity, we questioned whether HIV infection, even if successfully treated, or AUD alone results in signs of accelerated white matter aging and whether HIV+AUD comorbidity further accelerates brain aging. METHODS: Longitudinal magnetic resonance imaging-FLAIR data were acquired over a 15-year period from 179 control individuals, 204 participants with AUD, 70 participants with HIV, and 75 participants with comorbid HIV+AUD. White matter hyperintensity (WMH) volumes were quantified and localized, and their functional relevance was examined with cognitive and motor testing. RESULTS: The 3 diagnostic groups each had larger WMH volumes than the control group. Although all 4 groups exhibited accelerating volume increases with aging, only the HIV groups showed faster WMH enlargement than control individuals; the comorbid group showed faster acceleration than the HIV-only group. Sex and HIV infection length, but not viral suppression status, moderated acceleration. Correlations emerged between WMH volumes and attention/working memory and executive function scores of the AUD and HIV groups and between WMH volumes and motor skills in the 3 diagnostic groups. CONCLUSIONS: Even treated HIV can show accelerated aging, possibly from treatment sequelae or legacy effects, and notably from AUD comorbidity. WMH volumes may be especially relevant for tracking HIV and AUD brain health because each condition is associated with liability for hypertensive processes, for which WMHs are considered a marker.

Self-Assembled nanoparticles of natural bioactive molecules enhance the delivery and efficacy of paclitaxel in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Paclitaxel (PTX) is a well-established and highly effective anti-cancer drug for peripheral solid tumors. However, the application of PTX in GBM is hindered by several limitations, including poor water solubility, restricted entry across the blood-brain barrier (BBB), and enhanced excretion by efflux transporters. P-glycoprotein (P-gp) is a crucial efflux transporter that is abundantly present in cerebral vascular endothelial cells and GBM cells. It plays a significant role in the exocytosis of PTX within tumor tissues. METHODS: Recently, we have developed a novel technique for creating self-assembled nanoparticles utilizing a range of natural bioactive molecules. These nanoparticles can encapsulate insoluble drugs and effectively cross the BBB. In additional, we revealed that certain nanoparticles have the potential to act as P-gp inhibitors, thereby reducing the excretion of PTX. In this study, we conducted a screening of bioactive molecular nanoparticles to identify those that effectively inhibit the function of P-gp transporters. RESULTS: Among the candidates, we identified ursolic acid nanoparticles (UA NPs) as the P-gp inhibitors. Furthermore, we prepared co-assembled UA NPs embedded with paclitaxel, referred to as UA-PTX NPs. Our results demonstrate that UA-PTX NPs can enhance the blood concentration of PTX, facilitate its entry into the BBB, and inhibit the function of P-gp, resulting in a decrease in the excretion of PTX. This discovery effectively addressed the above three issues associated with the use of PTX in glioma treatment. CONCLUSIONS: UA-PTX NPs demonstrate strong anti-tumor effects and show great potential for treating GBM.

Selenomethionine protects the liver from dietary deoxynivalenol exposure via Nrf2/PPARγ-GPX4-ferroptosis pathway in mice.

Deoxynivalenol (DON) is a significant Fusarium toxin that has gained global attention due to its high frequency of contamination in food and feed. It was reported to have hepatotoxicity, immunotoxicity, and reproduction toxicity in organs. On the other hand, Selenomethionine (SeMet) was proven to have anti-oxidation, tissue repairing, immunity improvement, and antifungal mycotoxin infection functions. However, the molecular mechanism by which SeMet alleviates DON damage is not yet clear. C57BL/6 mice were randomly divided into three groups, Se-A and Se-A+DON were fed with a diet containing 0.2 mg/kg Se whereas Se-S+DON were fed with a diet of 1.0 mg/kg Se. After feeding for four weeks, the mice were gavaged for 21 days with DON (2.0 mg/kg BW) or ultrapure water once per day. In the present study, we showed that SeMet significantly decreased the lipid peroxidation product malondialdehyde, and increased activities of antioxidant enzymes superoxide dismutase and total antioxidant capacity after DON exposure. In addition, our investigation revealed that SeMet regulated pathways related to lipid synthesis and metabolisms, and effectively mitigated DON-induced liver damage. Moreover, we have discovered that SeMet downregulation of N-acylethanolamine and HexCer accumulation induced hepatic lipotoxicity. Further study showed that SeMet supplementation increased protein levels of glutathione peroxidase 4 (GPX4), peroxisome proliferator-activated receptor γ (PPARγ), nuclear erythroid 2-related factor 2 (Nrf2), and upregulated target proteins, indicating suppression of oxidative stress in the liver. Meanwhile, we found that SeMet significantly reduced the DON-induced protein abundances of Bcl2, Beclin1, LC3B and proteins related to ferroptosis (Lpcat3, and Slc3a2), and downregulation of Slc7a11. In conclusion, SeMet protected the liver from damage by enhancing the Nrf2/PPARγ-GPX4-ferroptosis pathway, inhibiting lipid accumulation and hepatic lipotoxicity. The findings of this study indicated that SeMet has a positive impact on liver health by improving antioxidant capacity and relieving lipotoxicity in toxin pollution.

Identification and molecular binding mechanism of novel pancreatic lipase and cholesterol esterase inhibitory peptides from heat-treated adzuki bean protein hydrolysates.

Heat-treated adzuki bean protein hydrolysates exhibit lipid-reducing properties; however, few studies have reported pancreatic lipase (PL) and cholesterol esterase (CE) inhibitory effects and elucidated the underlying mechanisms. In this study, we accomplished the identification of antiobesity peptides through peptide sequencing, virtual screening, and in vitro experiments. Furthermore, the mechanisms were investigated via molecular docking. The findings reveal that the action of pepsin and pancreatin resulted in the transformation of intact adzuki bean protein into smaller peptide fragments. The < 3 kDa fraction exhibited a high proportion of hydrophobic amino acids and displayed superior inhibitory properties for both PL and CE. Five novel antiobesity peptides (LLGGLDSSLLPH, FDTGSSFYNKPAG, IWVGGSGMDM, YLQGFGKNIL, and IFNNDPNNHP) were identified as PL and CE inhibitors. Particularly, IFNNDPNNHP exhibited the most robust biological activity. These peptides exerted their inhibitory action on PL and CE by occupying catalytic or substrate-binding sites through hydrogen bonds, hydrophobic interactions, salt bridges, and π-π stacking.

Qingjie decoction attenuated E.coli-induced diarrhea by regulating energy metabolism and alleviating inflammation based on network analysis and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Diarrhea is a frequently encountered gastrointestinal complication in clinical practice, and E. coli is one of the main causative agents. Although Qingjie decoction (QJD) has been shown to be highly effective in treating diarrhea by eliminating heat-toxin, the underlying molecular mechanisms and pathways of QJD remain unclear. AIM OF REVIEW: The aim of this research was to explore the effects and fundamental mechanism of QJD on diarrhea induced by E.coli in rats. MATERIALS AND METHODS: Initially, we used UHPLC-MS/MS analysis to identify the chemical composition of QJD. Then, we constructed a visualization network using network pharmacology. Next, we utilized metabolomics to identify differentially expressed metabolites of QJD that are effective in treating diarrhea. RESULTS: The chemical composition of QJD was analyzed using UHPLC-MS/MS, which identified a total of 292 components. Using a network pharmacology approach, 127 bioactive compounds of QJD were screened, targeting 171 potential diarrhea treatment targets. TNF-α, IL-6, IL-1ß, and CAT were identified as important targets through visualizing the PPI network. Enrichment analysis demonstrated significant enrichment in the TNF signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. QJD showed beneficial effects, such as increased body weight, decreased fecal water content, and reduced inflammatory cell infiltration in the duodenum and colon, as well as maintaining the structure of the duodenum and colon. Metabolomic analysis revealed 32 differentially expressed metabolites in the control, model and QJD-H groups, including glucose, valine, and cysteine. Functional analysis indicated that differential metabolites were related to energy metabolism, including glucose metabolism, TCA cycle, and amino acid metabolism. CONCLUSION: QJD significantly increased body weight, decreased water content in feces, relieved inflammatory cell infiltration, maintained the structure of duodenum and colon. Combining network analysis and metabolomics, QJD exerted therapeutic effects by inhibiting inflammation and oxidative stress, regulating glucose metabolism, tricarboxylic acid metabolism, and amino acid metabolism.

Enrichment efficiency of lutein in eggs and its function in improving fatty liver hemorrhagic syndrome in aged laying hens.

In this study, we evaluated the enrichment efficiency of lutein in eggs and its function in preventing fatty liver hemorrhagic syndrome (FLHS) in aged laying hens. Five groups of laying hens (65 wk old) were fed basal diets supplemented with 0, 30, 60, 90, or 120 mg/kg of lutein. The supplementation period lasted 12 wk followed by 2 wk of lutein depletion in feed. The results revealed that lutein efficiently enriched the egg yolks and improved their color with a significant increase in relative redness (P < 0.001). Lutein accumulation increased in the egg yolk until day 10, then depletion reached a minimum level after 14 d. Overall, zeaxanthin content in all the groups was similar throughout the experimental period. However, triglycerides and total cholesterol were significantly decreased in the liver (P < 0.05) but not significantly different in the serum (P > 0.05). In the serum, the lipid metabolism enzyme acetyl-CoA synthetase was significantly reduced (P < 0.05), whereas dipeptidyl-peptidase 4 was not significantly different (P > 0.05), and there was no statistical difference of either enzyme in the liver (P > 0.05). Regarding oxidation and inflammation-related indexes, malondialdehyde, tumor necrosis factors alpha, interleukin-6, and interleukin-1 beta were decreased, whereas superoxide dismutase and total antioxidant capacity increased in the liver (P < 0.001). The function of lutein for the same indexes in serum was limited. It was concluded that lutein efficiently enriched the egg yolk of old laying hens to improve their color and reached the highest level on day 10 without being subject to a significant conversion into zeaxanthin. At the same time, lutein prevented liver steatosis in aged laying hens by exerting strong antioxidant and anti-inflammatory functions, but also through the modulation of lipid metabolism, which may contribute to reducing the incidence of FLHS in poultry.

Approaching national climate targets in China considering the challenge of regional inequality.

Achievement of national climate targets and the corresponding costs would entirely depend on regional actions within the country. However, because of substantial inequalities and heterogeneities among regions, especially in developing economies, aggressive or uniform actions may exacerbate inequity and induce huge economic losses, which in turn challenges the national climate pledges. Hence, this study extends prior research by proposing economically optimal strategies that can achieve national climate targets and ensure the greatest local and national benefits as well as regional equality. Focusing on the biggest developing country China, we find this strategy can avoid up to 1.54% of cumulative GDP losses for approaching carbon neutrality, and more than 90% of regions would obtain economic gains compared either with existing independently launched targets or with the uniform strategy that all regions achieve peak carbon emissions before 2030. We also provide optimal carbon mitigation pathways to regional peak carbon, carbon intensity and energy consumption.

Imputing Brain Measurements Across Data Sets via Graph Neural Networks.

Publicly available data sets of structural MRIs might not contain specific measurements of brain Regions of Interests (ROIs) that are important for training machine learning models. For example, the curvature scores computed by Freesurfer are not released by the Adolescent Brain Cognitive Development (ABCD) Study. One can address this issue by simply reapplying Freesurfer to the data set. However, this approach is generally computationally and labor intensive (e.g., requiring quality control). An alternative is to impute the missing measurements via a deep learning approach. However, the state-of-the-art is designed to estimate randomly missing values rather than entire measurements. We therefore propose to re-frame the imputation problem as a prediction task on another (public) data set that contains the missing measurements and shares some ROI measurements with the data sets of interest. A deep learning model is then trained to predict the missing measurements from the shared ones and afterwards is applied to the other data sets. Our proposed algorithm models the dependencies between ROI measurements via a graph neural network (GNN) and accounts for demographic differences in brain measurements (e.g. sex) by feeding the graph encoding into a parallel architecture. The architecture simultaneously optimizes a graph decoder to impute values and a classifier in predicting demographic factors. We test the approach, called Demographic Aware Graph-based Imputation (DAGI), on imputing those missing Freesurfer measurements of ABCD (N=3760; minimum age 12 years) by training the predictor on those publicly released by the National Consortium on Alcohol and Neurodevelopment in Adolescence (NCANDA, N=540). 5-fold cross-validation on NCANDA reveals that the imputed scores are more accurate than those generated by linear regressors and deep learning models. Adding them also to a classifier trained in identifying sex results in higher accuracy than only using those Freesurfer scores provided by ABCD.