Folic Acid Rescues Dopaminergic Neurons in MPTP-Induced Mice by Inhibiting the NLRP3 Inflammasome and Ameliorating Mitochondrial Impairment.

Parkinson's disease (PD) is marked by the degeneration of dopaminergic neurons of the substantia nigra (SN), with neuroinflammation and mitochondrial dysfunction being key contributors. The neuroprotective potential of folic acid (FA) in the dopaminergic system of PD was assessed in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model. MPTP (20 mg/kg of body weight) was administered to C57BL/6J mice to simulate PD symptoms followed by FA treatment (5 mg/kg of body weight). Behavioral tests, pole, rotarod, and open-field tests, evaluated motor function, while immunohistochemistry, ELISA, RT-qPCR, and Western blotting quantified neuroinflammation, oxidative stress markers, and mitochondrial function. FA supplementation considerably improved motor performance, reduced homocysteine levels and mitigated oxidative damage in the SN. The FA-attenuated activation of the NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome lessened glial cell activity and reduced neuroinflammation. At the molecular level, FA reduced DNA damage, downregulated phosphorylated p53, and induced the expression of peroxisome proliferator-activated receptor α coactivator 1α (PGC-1α), enhancing mitochondrial function. Therefore, FA exerts neuroprotection in MPTP-induced PD by inhibiting neuroinflammation via NLRP3 inflammasome suppression and promoting mitochondrial integrity through the p53-PGC-1α pathway. Notable limitations of our study include its reliance on a single animal model and the incompletely elucidated mechanisms underlying the impact of FA on mitochondrial dynamics. Future investigations will explore the clinical utility of FA and its molecular mechanisms, further advancing it as a potential therapeutic for managing and delaying the progression of PD.

MHD-Net: Memory-Aware Hetero-Modal Distillation Network for Thymic Epithelial Tumor Typing With Missing Pathology Modality.

Fusing multi-modal radiology and pathology data with complementary information can improve the accuracy of tumor typing. However, collecting pathology data is difficult since it is high-cost and sometimes only obtainable after the surgery, which limits the application of multi-modal methods in diagnosis. To address this problem, we propose comprehensively learning multi-modal radiology-pathology data in training, and only using uni-modal radiology data in testing. Concretely, a Memory-aware Hetero-modal Distillation Network (MHD-Net) is proposed, which can distill well-learned multi-modal knowledge with the assistance of memory from the teacher to the student. In the teacher, to tackle the challenge in hetero-modal feature fusion, we propose a novel spatial-differentiated hetero-modal fusion module (SHFM) that models spatial-specific tumor information correlations across modalities. As only radiology data is accessible to the student, we store pathology features in the proposed contrast-boosted typing memory module (CTMM) that achieves type-wise memory updating and stage-wise contrastive memory boosting to ensure the effectiveness and generalization of memory items. In the student, to improve the cross-modal distillation, we propose a multi-stage memory-aware distillation (MMD) scheme that reads memory-aware pathology features from CTMM to remedy missing modal-specific information. Furthermore, we construct a Radiology-Pathology Thymic Epithelial Tumor (RPTET) dataset containing paired CT and WSI images with annotations. Experiments on the RPTET and CPTAC-LUAD datasets demonstrate that MHD-Net significantly improves tumor typing and outperforms existing multi-modal methods on missing modality situations.

Evidence from an Avian Embryo Model that Zinc-Inducible MT4 Expression Protects Mitochondrial Function Against Oxidative Stress.

BACKGROUND: Metallothioneins (MTs) have a strong affinity for zinc (Zn) and remain at a sufficiently high level in mitochondria. As the avian embryo is highly susceptible to oxidative damage and relatively easy to manipulate in a naturally closed chamber, it is an ideal model of the effects of oxidative stress on mitochondrial function. However, the protective roles and molecular mechanisms of Zn-inducible protein expression on mitochondrial function in response to various stressors are poorly understood. OBJECTIVES: The study aimed to investigate the mechanisms by which Zn-induced MT4 expression protects mitochondrial function and energy metabolism subjected to oxidative stress using the avian embryo and embryonic primary hepatocyte models. METHODS: First, we investigated whether MT4 expression alters mitochondrial function. Then, we examined the effects of Zn-induced MT4 overexpression and MT4 silencing on embryonic primary hepatocytes from breeder hens fed a normal Zn diet subjected to a tert-butyl hydroperoxide (BHP) oxidative stress challenge during incubation. In vivo, the avian embryos from hens fed the Zn-deficient and Zn-adequate diets were used to determine the protective roles of Zn-induced MT4 expression on the function of mitochondria exposed to oxidative stress induced by in ovo BHP injection. RESULTS: An in vitro study revealed that Zn-induced MT4 expression reduced reactive oxygen species accumulation in primary hepatocytes. MT4 silencing exacerbated BHP-mediated mitochondrial dysfunction whereas Zn-inducible MT4 overexpression mitigated it. Another in vivo study disclosed that maternal Zn-induced MT4 expression protected mitochondrial function in chick embryo hepatocytes against oxidative stress by inhibiting the peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)/peroxisome proliferators-activated receptor-γ (PPAR-γ) pathway. CONCLUSION: This study underscores the potential protective roles of Zn-induced MT4 expression via the downregulation of the PGC-1α/PPAR-γ pathway on mitochondrial function stimulated by the stress challenge in the primary hepatocytes in an avian embryo model. Our findings suggested that Zn-induced MT4 expression could provide a new therapeutic target and preventive strategy for repairing mitochondrial dysfunction in disease.

Bifidobacterium animalis subsp. lactis F1-7 Alleviates Lipid Accumulation in Atherosclerotic Mice via Modulating Bile Acid Metabolites to Downregulate Intestinal FXR.

The dysfunction of intestinal microbiota and bile acid metabolism is related to the pathogenesis of atherosclerosis. This study we explored the mechanism of Bifidobacterium animalis subsp. lactis F1-7 (Bif. animalis F1-7), improving atherosclerosis by regulating the bile acid metabolism and intestinal microbiota in the ApoE-/- mice. The Bif. animalis F1-7 effectively reduced aortic plaque accumulation and improved the serum and liver lipid levels in atherosclerotic mice. The untargeted metabolomics revealed that Bif. animalis F1-7 reduced the glycine-conjugated bile acids and the levels of differential metabolite lithocholic acid (LCA) significantly. Downregulation of LCA decreased the intestinal levels of the farnesoid X-activated receptor (FXR) and regulated the bile acid metabolism through the FXR/FGF15/CYP7A1 pathway. Furthermore, the 16srRNA gene sequencing analysis revealed that structural changes in intestinal microbiota with an increase in the abundance of Bifidobacterium, Lactobacillus, Faecalibaculum, Desulfovibrio, and a decrease in Dubosiella, Clostridium_sensu_stricto_1, and Turicibacter following the Bif. animalis F1-7 intervention. Correlation analysis showed that the changes in intestinal microbiota mentioned above were significantly correlated with bile acid metabolism in atherosclerotic mice. In conclusion, this study sheds light on the mechanisms by which Bif. animalis F1-7 regulates atherosclerosis.

MGIML: Cancer Grading with Incomplete Radiology-Pathology Data via Memory Learning and Gradient Homogenization.

Taking advantage of multi-modal radiology-pathology data with complementary clinical information for cancer grading is helpful for doctors to improve diagnosis efficiency and accuracy. However, radiology and pathology data have distinct acquisition difficulties and costs, which leads to incomplete-modality data being common in applications. In this work, we propose a Memory-and Gradient-guided Incomplete Modal-modal Learning (MGIML) framework for cancer grading with incomplete radiology-pathology data. Firstly, to remedy missing-modality information, we propose a Memory-driven Hetero-modality Complement (MH-Complete) scheme, which constructs modal-specific memory banks constrained by a coarse-grained memory boosting (CMB) loss to record generic radiology and pathology feature patterns, and develops a cross-modal memory reading strategy enhanced by a fine-grained memory consistency (FMC) loss to take missing-modality information from well-stored memories. Secondly, as gradient conflicts exist between missing-modality situations, we propose a Rotation-driven Gradient Homogenization (RG-Homogenize) scheme, which estimates instance-specific rotation matrices to smoothly change the feature-level gradient directions, and computes confidence-guided homogenization weights to dynamically balance gradient magnitudes. By simultaneously mitigating gradient direction and magnitude conflicts, this scheme well avoids the negative transfer and optimization imbalance problems. Extensive experiments on CPTAC-UCEC and CPTAC-PDA datasets show that the proposed MGIML framework performs favorably against state-of-the-art multi-modal methods on missing-modality situations.

A Healthy, Low-Carbohydrate Diet During Pregnancy Is Associated With a Reduced Risk of Gestational Diabetes Mellitus.

CONTEXT: Evidence on the associations of low-carbohydrate diet (LCD) during pregnancy with gestational diabetes mellitus (GDM) has been limited and inconsistent. OBJECTIVE: We aimed to prospectively evaluate the risk of GDM associated with the LCD considering the quality of macronutrients. METHODS: All participants were from a prospective cohort in Wuhan, China. The overall, healthy LCD (emphasizing low-quality carbohydrates, plant protein, and unsaturated fat), and unhealthy LCD (emphasizing high-quality carbohydrates, animal protein, and saturated fat) scores were calculated according to the percentage of energy intake from carbohydrates, protein, and fat. GDM was screened by a 75-g oral glucose tolerance test between 24 and 28 weeks. Poisson regression models were used to calculate relative risks (RRs) and 95% CIs. RESULTS: Of 2337 pregnant women, 257 (11.0%) were diagnosed with GDM. Overall LCD score was not associated with risk of GDM, but the healthy and unhealthy LCD scores were associated with the risk of GDM. The multivariable-adjusted RRs (95% CI) were 0.68 (0.49-0.94) and 1.52 (1.11-2.08) for healthy and unhealthy LCD scores comparing the highest with the lowest quartile. Substituting high-quality carbohydrates for low-quality carbohydrates and animal protein, and substituting unsaturated fat for saturated fat, were associated with a 13% to 29% lower risk of GDM. CONCLUSION: A healthy LCD during pregnancy characterized by high-quality carbohydrates, plant protein, and unsaturated fat was associated with a lower risk of GDM, whereas an unhealthy LCD consisting of low-quality carbohydrates, animal protein, and saturated fat was associated with a higher risk of GDM.

Astaxanthin Protects against Alcoholic Liver Injury via Regulating Mitochondrial Redox Balance and Calcium Homeostasis.

Increasing evidence points to the critical role of calcium overload triggered by mitochondrial dysfunction in the development of alcoholic liver disease (ALD). As an important organelle for aerobic respiration with a double-layered membrane, mitochondria are pivotal targets of alcohol metabolism-mediated lipid peroxidation, wherein mitochondria-specific phospholipid cardiolipin oxidation to 4-hydroxynonenal (4-HNE) ultimately leads to mitochondrial integrity and function impairment. Therefore, it is absolutely essential to identify effective nutritional intervention targeting mitochondrial redox function for an alternative therapy of ALD, in order to compensate for the difficulty in achieving alcohol withdrawal due to addiction. In this study, we confirmed the significant advantages of astaxanthin (AX) against alcohol toxicity among various carotenoids via cell experiments and identified the potential in mitochondrion morphogenesis and calcium signaling pathway by bioinformatics analysis. The ALD model of Sprague-Dawley (SD) rats was also generated to investigate the effectiveness of AX on alcohol-induced liver injury, and the underlying mechanisms were further explored. AX intervention attenuated alcohol-induced oxidative stress and lipid peroxidation as well as mitochondrial dysfunction characterized by degenerative morphology changes and collapsed membrane potential. Also, AX reduced the production of 4-HNE by activating the Nrf2-ARE signaling pathway, which is closely associated with the redox balance of mitochondria. In addition, relieved mitochondrial Ca2+ accumulation caused by AX was observed both in vivo and in vitro. Furthermore, we revealed the structure-activity relationship of AX and mitochondrial membrane channel proteins MCU and VDAC1, implying potential acting targets. Altogether, our data indicated a new mechanism of AX intervention which protects against alcohol-induced liver injury through restoring redox balance and Ca2+ homeostasis in mitochondria, as well as provided novel insights into the development of AX as a therapeutic option for the management of ALD.

Maternal Folic Acid Supplementation during Pregnancy Prevents Hepatic Steatosis in Male Offspring of Rat Dams Fed High-Fat Diet, Which Is Associated with the Regulation of Gut Microbiota.

Maternal dietary patterns during pregnancy have been demonstrated to impact the structure of the gut microbiota in offspring, altering their susceptibility to diseases. This study is designed to elucidate whether the impact of folic acid supplementation during pregnancy on hepatic steatosis in male offspring of rat dams exposed to a high-fat diet (HFD) is related to gut-liver axis homeostasis. In this study, female rats were administered a HFD and simultaneously supplemented with 5 mg/kg folic acid throughout their pregnancy. Histopathological examination showed that folic acid supplementation effectively ameliorated hepatic lipid accumulation and inflammatory infiltrate in male offspring subjected to a maternal HFD. Maternal folic acid supplementation reduced the abundance of Desulfobacterota and the Firmicutes/Bacteroidota (F/B) ratio in male offspring. The expression of tight junction proteins in the colon was significantly upregulated, and the serum LPS level was significantly reduced. Furthermore, there was a notable reduction in the hepatic expression of the TLR4/NF-κB signaling pathway and subsequent inflammatory mediators. Spearman's correlation analysis revealed significant associations between hepatic inflammation-related indices and several gut microbiota, particularly Desulfobacterota and Lactobacillus. With a reduction in hepatic inflammation, the expression of PPAR-α was upregulated, and the expression of SREBP-1c and its downstream lipid metabolism-related genes was downregulated. In summary, folic acid supplementation during pregnancy modulates gut microbiota and enhances intestinal barrier integrity in male offspring of HFD dams. This helps reduce the LPS leakage and suppress the expression of TLR4/NF-κB pathway in the liver, thereby improving lipid metabolism disorders, and alleviating hepatic steatosis.

Folic Acid Protects against Ethanol-Induced Hepatic Mitophagy Imbalance by ROS Scavenging and Attenuating the Elevated Hcy Levels.

Ample evidence indicates that ethanol-induced oxidative stress and mitochondrial dysfunction are central to the pathogenesis of alcoholic liver disease (ALD). As an adaptive quality control mechanism, mitophagy removes dysfunctional mitochondria to avert hepatic lesions in ALD. Folic acid exhibits potential radical scavenging properties and has been proven to ameliorate mitochondrial disorder in oxidative stress-related diseases. In this study, we aimed to uncover the mitophagy regulatory effects of folic acid in a 10w alcohol C57BL/6J mice feeding model (56% v/v) and L02 cells model cultured with ethanol (2.5% v/v). The results showed that folic acid alleviates ethanol-induced liver injury, decreasing oxidative stress and restoring liver enzyme. Furthermore, folic acid improved the mitochondrial function and inhibited ethanol-activated mitophagy through decreasing PINK1-Parkin and Drp1 expression, which inhibited the release of mitochondrial cytochrome C to the cytoplasm, preventing hepatocyte apoptosis. Intriguingly, folic acid attenuates the elevated hepatic homocysteine (Hcy) level. Additionally, the pretreatment of L02 cells with folic acid also ameliorated Hcy-induced oxidative damage, mitochondrial fission, and mitophagy. In summary, these results suggest that folic acid has beneficial effects in mitophagy remodeling by ROS scavenging and facilitating Hcy metabolism and could be developed as a potential therapeutic agent against ALD.

Dietary Folic Acid Supplementation Attenuates Maternal High-Fat Diet-Induced Fetal Intrauterine Growth Retarded via Ameliorating Placental Inflammation and Oxidative Stress in Rats.

The placenta is particularly susceptible to inflammation and oxidative stress, leading to placental vascular dysfunction and placental insufficiency, which is associated with fetal intrauterine growth restriction (IUGR). It is unknown whether folic acid (FA) supplementation can alleviate high-fat diet-induced IUGR in rats by improving placental function. In this study, pregnant rats were randomized into one of four diet-based groups: (1) control diet (CON), (2) control diet supplemented with FA, (3) high-fat diet (HFD), and (4) high-fat diet supplemented with FA (HFD + FA). Dams were sacrificed at gestation day 18.5 (GD18.5). The results indicated that dietary FA supplementation normalized a maternal HFD-induced decrease in fetal weight. The decrease in placental efficiency, labyrinth zone (LZ) area, blood sinusoid area, vascular density, and the levels of angiogenesis factors induced by a maternal HFD were alleviated by the addition of FA, suggesting that FA supplementation can alleviate placental vascular dysplasia. Furthermore, FA supplementation increased the protein expressions of SIRT1, inhibited NF-κB transcriptional activation, attenuated the levels of NF-κB/downstream pro-inflammatory cytokines, induced Nrf2 activation, and increased downstream target protein expression. In conclusion, we found that dietary FA supplementation during pregnancy could improve maternal HFD-induced IUGR by alleviating placental inflammation and oxidative stress, which may be associated with the regulation of SIRT1 and its mediated NF-κB and Nrf2 signaling pathways.

Fucoidan from Saccharina japonica Alleviates Hyperuricemia-Induced Renal Fibrosis through Inhibiting the JAK2/STAT3 Signaling Pathway.

Fucoidan is a native sulfated polysaccharide mainly isolated from brown seaweed, with diverse pharmacological activities, such as anti-inflammatory and antifibrosis. Hyperuricemia (HUA) is a common metabolic disease worldwide and mainly causes hyperuricemic nephropathy, including chronic kidney disease and end-stage renal fibrosis. The present study investigated the protective function of fucoidan in renal fibrosis and its pharmacological mechanism. The renal fibrotic model was established with the administration of potassium oxonate for 10 weeks. The protein levels of related factors were assessed in HUA mice by an enzyme-linked immunosorbent assay (ELISA) and western blotting. The results showed that fucoidan significantly reduced the levels of serum uric acid, blood urea nitrogen (BUN), α-smooth muscle actin (α-SMA), and collagen I, and improved kidney pathological changes. Furthermore, renal fibrosis had been remarkably elevated through the inhibition of the epithelial-to-mesenchymal transition (EMT) progression after fucoidan intervention, suppressing the Janus kinase 2 (JAK2) signal transducer and activator of transcription protein 3 (STAT3) signaling pathway activation. Together, this study provides experimental evidence that fucoidan may protect against hyperuricemia-induced renal fibrosis via downregulation of the JAK2/STAT3 signaling pathway.

Remnant Cholesterol Is Associated With Gestational Diabetes Mellitus: A Cohort Study.

CONTEXT: The association between remnant cholesterol (RC) and gestational diabetes mellitus (GDM) risk is unclear. OBJECTIVE: This study investigated the association between RC and GDM. METHODS: We used data from the Tongji Maternal and Child Health Cohort, a prospective cohort study in China. Fasting lipid concentrations were measured around 16 weeks' gestation. RC was calculated as total cholesterol minus low-density lipoprotein cholesterol and high-density lipoprotein cholesterol. GDM was diagnosed by a 75-g oral glucose tolerance test at 24 to 28 weeks' gestation. Log-Poisson regression models were performed to estimate relative risks (RRs) of GDM across quartiles of RC levels and triglyceride (TG) levels after adjustment for potential confounders. TG and RC were mutually adjusted. RESULTS: Among 2528 women, 256 (10.1%) developed GDM. The adjusted RRs (95% CIs) for GDM across increasing quartiles of RC were 1.00 (reference), 1.35 (0.91, 1.99), 1.68 (1.16, 2.45), and 1.73 (1.19, 2.50), respectively. Compared to pregnant women without 3 risk indicators (TG <2.08 mmol/L, RC <0.40 mmol/L, and pre-BMI <24.0 kg/m2), the risk of GDM was elevated in those with normal pre-BMI but high RC (aRR: 1.54; 95% CI: 1.08, 2.19) or high TG (aRR: 2.15; 95% CI: 1.33, 3.49). For those with all 3 risk indicators, the risk of GDM was the highest (aRR: 4.80; 95% CI: 3.20, 7.18). CONCLUSION: Elevated RC levels were associated with the increased risk of GDM and independent of traditional risk factors. Pregnant women with high pre-BMI, high TG, and high RC were at greatly increased risk of GDM.

Longitudinal plasma magnesium status during pregnancy and the risk of gestational diabetes mellitus: a prospective cohort study.

Emerging evidence has shown that magnesium (Mg) was associated with type 2 diabetes while few focused on abnormal glucose metabolism during pregnancy. The study is aimed at investigating the association between longitudinal changes in plasma Mg during pregnancy and subsequent risk of gestational diabetes (GDM) and exploring the possible influence of iron supplementation on the changes of plasma Mg levels. One thousand seven hundred fifty-six pregnant women from Tongji Maternal and Child Health Cohort (TMCHC) were involved. Blood samples were collected at gestational weeks 17.0 ± 0.9 and later 26.2 ± 1.4. Plasma Mg was measured by inductively coupled plasma mass spectrometry (ICP-MS) with decline rates calculated. Information on general characteristics and iron supplementation was collected by questionnaires. Oral glucose tolerance test (OGTT) was conducted at 24-28 gestational weeks to diagnose GDM. Poisson regression with robust error variance was used to estimate relative risks (RR) of GDM. Median concentrations of plasma Mg were 0.69 mmol/L and 0.63 mmol/L respectively at two collections. The prevalence of hypomagnesemia at the first collection was 73% and associated with a 1.59 (95%CI: 1.07, 2.37) fold risk of GDM. Adjusted RRs were 1.74 (95%CI: 1.06, 2.83) and 2.44 (95%CI: 1.54, 3.85) for women with hypomagnesemia and followed more tertile (T2 and T3 vs. T1) of Mg decrement. Iron supplementation above 30 mg/day was found associated with more Mg decrement (25.5% and 27.5% in T2 and T3 vs. 19.5% in T1). In conclusion, hypomagnesemia during pregnancy is prevalent and associated with increased GDM risk, especially in women followed by more plasma Mg decrement during pregnancy. High-dose iron supplementation may involve more plasma Mg decrement.

Maternal zinc alleviates tert-butyl hydroperoxide-induced mitochondrial oxidative stress on embryonic development involving the activation of Nrf2/PGC-1α pathway.

BACKGROUND: Mitochondrial dysfunction induced by excessive mitochondrial reactive oxygen species (ROS) damages embryonic development and leads to growth arrest. OBJECTIVE: The purpose of this study is to elucidate whether maternal zinc (Zn) exert protective effect on oxidative stress targeting mitochondrial function using an avian model. RESULT: In ovo injected tert-butyl hydroperoxide (BHP) increases (P < 0.05) hepatic mitochondrial ROS, malondialdehyde (MDA) and 8-hydroxy-2-deoxyguanosine (8-OHdG), and decreases (P < 0.05) mitochondrial membrane potential (MMP), mitochondrial DNA (mtDNA) copy number and adenosine triphosphate (ATP) content, contributing to mitochondrial dysfunction. In vivo and in vitro studies revealed that Zn addition enhances (P < 0.05) ATP synthesis and metallothionein 4 (MT4) content and expression as well as alleviates (P < 0.05) the BHP-induced mitochondrial ROS generation, oxidative damage and dysfunction, exerting a protective effect on mitochondrial function by enhancing antioxidant capacity and upregulating the mRNA and protein expressions of Nrf2 and PGC-1α. CONCLUSIONS: The present study provides a new way to protect offspring against oxidative damage by maternal Zn supplementation through the process of targeting mitochondria involving the activation of Nrf2/PGC-1α signaling.

Guided Colorization Using Mono-Color Image Pairs.

Compared to color images captured by conventional RGB cameras, monochrome (mono) images usually have higher signal-to-noise ratios (SNR) and richer textures due to the lack of color filter arrays in mono cameras. Therefore, using a mono-color stereo dual-camera system, we can integrate the lightness information of target monochrome images with the color information of guidance RGB images to accomplish image enhancement in a colorization manner. In this work, based on two assumptions, we introduce a novel probabilistic-concept guided colorization framework. First, adjacent contents with similar luminance are likely to have similar colors. By lightness matching, we can utilize colors of the matched pixels to estimate the target color value. Second, by matching multiple pixels from the guidance image, if more of these matched pixels have similar luminance values to the target one, we can estimate colors with more confidence. Based on the statistical distribution of multiple matching results, we retain the reliable color estimates as initial dense scribbles and then propagate them to the rest of the mono image. However, for a target pixel, the color information provided by its matching results is quite redundant. Hence, we introduce a patch sampling strategy to accelerate the colorization process. Based on the analysis of the posteriori probability distribution of the sampling results, we can use much fewer matches for color estimation and reliability assessment. To alleviate incorrect color propagation in the sparsely scribbled regions, we generate extra color seeds according to the existed scribbles to guide the propagation process. Experimental results show that, our algorithm can efficiently and effectively restore color images with higher SNR and richer details from the mono-color image pairs, and achieves good performance in solving the color bleeding problem.

Association of Breastfeeding Practices During the First 3 Months with Infant Sleep Trajectories: A Prospective Cohort Study.

BACKGROUND: Breastfeeding has numerous effects on maternal and child health. The effect of breastfeeding on infant sleep remains inconclusive. OBJECTIVES: We aimed to examine whether full breastfeeding (FBF) during the first 3 mo is associated with longitudinal infant sleep trajectories in their first 2 y of life. METHODS: The study was embedded in the Tongji Maternal and Child Health Cohort study. Information on infant feeding practices was collected at 3 mo of age, and maternal/child pairs were assigned to the FBF or the non-FBF group (including partially breastfeeding and exclusive formula feeding) on the basis of feeding practices during the first 3 mo of life. Sleep data of infants were obtained at 3, 6, 12, and 24 mo. Total, night, and day sleep trajectories across 3 to 24 mo were estimated with group-based models. Each sleep trajectory was differentiated on the basis of sleep duration at 3 mo (long/moderate/short) and the interval from 6 to 24 mo (moderate/short). Multinomial logistic regression was used to investigate the association of breastfeeding practices with infant sleep trajectories. RESULTS: Among the 4056 infants studied, 2558 (63.1%) received FBF for 3 mo. When compared with FBF infants, non-FBF infants had shorter sleep duration at 3, 6, and 12 mo (P < 0.01). Non-FBF infants were more likely to experience Moderate-Short (OR: 1.31; 95% CI: 1.06, 1.61) and Short-Short (OR: 1.56; 95% CI: 1.12, 2.16) total sleep trajectories and more likely to experience Moderate-Short (OR: 1.84; 95% CI: 1.22, 2.77), and Short-Moderate (OR: 1.40; 95% CI: 1.06, 1.85) night sleep trajectories than FBF infants. CONCLUSIONS: Full breastfeeding for ≥3 mo were positively associated with longer infant sleep duration. Infants fully breastfed were more likely to experience better sleep trajectories characterized by longer duration in their first 2 y of life. Full breastfeeding may benefit infants through healthy sleep.

Maternal yogurt consumption during pregnancy and infantile eczema: a prospective cohort study.

Maternal fermented food consumption during pregnancy was suggested to be beneficial for a healthy microbiome, and prevent infantile eczema. However, the association between yogurt and eczema has not been well investigated. To examine whether maternal yogurt consumption during pregnancy is associated with risk of infantile eczema, we performed a prospective mother-offspring cohort study in Wuhan, China. Maternal yogurt consumption in late pregnancy was assessed with a semi-quantitative food frequency questionnaire. The main outcomes were doctor-diagnosed infantile eczema collected at 3 and 6 months postpartum. Adjusted rate ratios (aRRs) were calculated by Poisson regression models adjusted for potential confounders. In our study, 182 (7.7%) of 2371 infants followed for 3 months and 84 (4.0%) of 2114 infants followed until 6 months reported doctor-diagnosed eczema. Compared to infants whose mothers had not consumed any yogurt, infants with mothers who consumed yogurt during late pregnancy had reduced risk of eczema between 3 and 6 months of age (aRR = 0.54, 95% CI 0.35-0.85); the reduction was pronounced in those with maternal yogurt intake >3 times per week (aRR = 0.48, 95% CI 0.28-0.82) and >50 g day-1 (aRR = 0.50, 95% CI 0.30-0.81). Moreover, infants with mothers who consumed yogurt showed decreased risk for recurrent eczema within the first 6 months (aRR = 0.46, 95% CI 0.22-0.98). In conclusion, this study found that maternal yogurt consumption during late pregnancy was related to a reduced incidence of eczema in infants aged 3 to 6 months, and recurrent eczema in the first 6 months of life.

CHD4 promotes acquired chemoresistance and tumor progression by activating the MEK/ERK axis.

AIMS: Chemoresistance remains a major challenge in gastric cancer (GC). Chromodomain helicase DNA-binding protein 4 (CHD4) mediated chromatin remodeling plays critical roles in various tumor types, but its role in chemoresistance in GC remains uncharacterized. METHODS: CHD4 expression was examined by immunohistochemistry and Western blotting. The role of CHD4 on cell proliferation and chemoresistance of GC was examined in vitro and in vivo. Immunoprecipitation and liquid chromatography-mass spectrometry were used to identify CHD4-binding proteins and a proximity ligation assay was used to explore protein-protein interaction. RESULTS: Chemoresistance is associated with upregulation of CHD4 in the tumor tissues of GC patients. Overexpression of CHD4 increased chemoresistance and cell proliferation. Knockdown of CHD4 induced cell apoptosis and cell cycle arrest. CHD4 mediates the decrease of the intracellular concentration of cisplatin by inducing drug efflux. Additionally, CHD4 promotes the interaction between ERK1/2 and MEK1/2, resulting in continuous activation of MEK/ERK pathway. Knockdown of CHD4 in GC increased sensitivity to chemotherapy and suppressed tumor growth in a mouse xenograft model. CONCLUSIONS: This study identifies CHD4 dominated multi-drug efflux as a promising therapeutic target for overcoming acquired chemoresistance in GC.

Dicoumarin with dimethyl thiocarbamate in the fluorescent detecting for Au3+ in water and cells.

Gold ions have high activity and cytotoxicity completely different from elemental gold. It is necessary and critical to develop Au3+ detection tools that are easy to operate, intuitive, inexpensive, and non-destructive testing. Here, we propose a novel two-photon fluorescent probe named DA for detecting Au3+, which is a rare combination of dicoumarin with dimethylthiocarbamate for the first time. Based on the PET mechanism, DA turns-on the fluorescence to yellow-green after specifically binds to Au3+, and the reaction is completed within 5 min. The detection limit is as low as 27.60 nM. Simultaneously, DA achieved qualitative and quantitative detection of Au3+ in environmental water samples, and fluorescence imaging of Au3+ in biological cells.