ABSTRACT
Aim: To evaluate the prognostic significance of CD44 variant v6 (CD44v6) and matrix metalloproteinases 2 (MMP2) expression in patients with surgically resected osteosarcoma. Methods: CD44v6 and MMP2 expression were immunohistochemically detected in 113 primary osteosarcoma patients at our institute between 2001 and 2019. Results: Both CD44v6 and MMP2 were independent predictors for metastasis-free and overall survival. An extended predictive range and improved sensitivity were observed when the combined effects of CD44v6 and MMP2 were considered. Specifically, patients with CD44v6+ and MMP2+ expression were more susceptible to lung metastasis and exhibited the poorest survival rates compared with the other groups. Conclusion: The combination of CD44v6 and MMP2 may serve as a precise prognostic indicator for predicting metastatic progression and survival outcomes in patients with osteosarcoma.
The most common type of bone cancer in children, teens and young adults is osteosarcoma, which often spreads to the lungs. With proper chemotherapy and surgery, many patients can recover, but if the diagnosis and treatment process go wrong, it could have serious consequences. The most common symptoms of osteosarcoma in its early stages are pain and swelling. The pain usually comes and goes, which can be easily mistaken for growing pains, resulting in a delayed diagnosis. In patients with metastatic (cancer cells spreading from the primary site to other parts of the body) osteosarcoma, the number of metastatic sites and whether they can be completely removed through surgery are factors that affect prognosis. So, starting appropriate treatment early for patients could effectively reduce tumor spread and increase survival time.
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To address the various challenges in aluminum surface defect detection, such as multiscale intricacies, sensitivity to lighting variations, occlusion, and noise, this study proposes the AluDef-ClassNet model. Firstly, a Gaussian difference pyramid is utilized to capture multiscale image features. Secondly, a self-attention mechanism is introduced to enhance feature representation. Additionally, an improved residual network structure incorporating dilated convolutions is adopted to increase the receptive field, thereby enhancing the network's ability to learn from extensive information. A small-scale dataset of high-quality aluminum surface defect images is acquired using a CCD camera. To better tackle the challenges in surface defect detection, advanced deep learning techniques and data augmentation strategies are employed. To address the difficulty of data labeling, a transfer learning approach based on fine-tuning is utilized, leveraging prior knowledge to enhance the efficiency and accuracy of model training. In dataset testing, our model achieved a classification accuracy of 97.6%, demonstrating significant advantages over other classification models.
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Maternal health and diet can have important consequences for offspring nutrition and metabolic health. During lactation, signals are communicated from the mother to the infant through milk via macronutrients, hormones, and bioactive molecules. In this study we designed experiments to probe the mother-milk-infant triad in the condition of normal maternal health and upon exposure to high fat diet (HFD) with or without concurrent metformin exposure. We examined maternal characteristics, milk composition and offspring metabolic parameters on postnatal day 16, prior to offspring weaning. We found that lactational HFD increased maternal adipose tissue weight, mammary gland adipocyte size, and altered milk lipid composition causing a higher amount of omega-6 (n6) long chain fatty acids and lower omega-3 (n3). Offspring of HFD dams were heavier with more body fat during suckling. Metformin (Met) exposure decreased maternal blood glucose and several milk amino acids. Offspring of met dams were smaller during suckling. Gene expression in the lactating mammary glands was impacted to a greater extent by metformin than HFD, but both metformin and HFD altered genes related to muscle contraction, indicating that these genes may be more susceptible to lactational stressors. Our study demonstrates the impact of common maternal exposures during lactation on milk composition, mammary gland function and offspring growth with metformin having little capacity to rescue the offspring from the effects of a maternal HFD during lactation.
Subject(s)
Mammary Glands, Human , Metformin , Animals , Dietary Fats/analysis , Dietary Fats/metabolism , Female , Humans , Lactation/metabolism , Metformin/pharmacology , Milk/metabolismABSTRACT
The early diagnosis of Alzheimer's disease (AD) can allow patients to take preventive measures before irreversible brain damage occurs. It can be seen from cross-sectional imaging studies of AD that the features of the lesion areas in AD patients, as observed by magnetic resonance imaging (MRI), show significant variation, and these features are distributed throughout the image space. Since the convolutional layer of the general convolutional neural network (CNN) cannot satisfactorily extract long-distance correlation in the feature space, a deep residual network (ResNet) model, based on spatial transformer networks (STN) and the non-local attention mechanism, is proposed in this study for the early diagnosis of AD. In this ResNet model, a new Mish activation function is selected in the ResNet-50 backbone to replace the Relu function, STN is introduced between the input layer and the improved ResNet-50 backbone, and a non-local attention mechanism is introduced between the fourth and the fifth stages of the improved ResNet-50 backbone. This ResNet model can extract more information from the layers by deepening the network structure through deep ResNet. The introduced STN can transform the spatial information in MRI images of Alzheimer's patients into another space and retain the key information. The introduced non-local attention mechanism can find the relationship between the lesion areas and normal areas in the feature space. This model can solve the problem of local information loss in traditional CNN and can extract the long-distance correlation in feature space. The proposed method was validated using the ADNI (Alzheimer's disease neuroimaging initiative) experimental dataset, and compared with several models. The experimental results show that the classification accuracy of the algorithm proposed in this study can reach 97.1%, the macro precision can reach 95.5%, the macro recall can reach 95.3%, and the macro F1 value can reach 95.4%. The proposed model is more effective than other algorithms.
Subject(s)
Alzheimer Disease , Early Diagnosis , Humans , Magnetic Resonance Imaging , Neural Networks, Computer , NeuroimagingABSTRACT
High-quality and complete human motion 4D reconstruction is of great significance for immersive VR and even human operation. However, it has inevitable self-scanning constraints, and tracking under monocular settings also has strict restrictions. In this paper, we propose a human motion capture system combined with human priors and performance capture that only uses a single RGB-D sensor. To break the self-scanning constraint, we generated a complete mesh only using the front view input to initialize the geometric capture. In order to construct a correct warping field, most previous methods initialize their systems in a strict way. To maintain high fidelity while increasing the easiness of the system, we updated the model while capturing motion. Additionally, we blended in human priors in order to improve the reliability of model warping. Extensive experiments demonstrated that our method can be used more comfortably while maintaining credible geometric warping and remaining free of self-scanning constraints.
Subject(s)
Posture , Humans , Motion , Reproducibility of ResultsABSTRACT
Screening potential plant species is a crucial consideration in phytoremediation technology. Our previous study demonstrated that Rhus chinensis Mill. seedlings had potentials for phytoremediation of Pb contaminated soil. However, its bioaccumulation and tolerance characteristics remain unclear. Seedling growth, LMWOAs secreted by roots, Pb subcellular distribution and chemical forms, and mineral elements in R. chinensis tissues were evaluated under different Pb concentrations (0, 25, 50, 100, 200 and 400â¯mg/L) in culture solution at 14â¯days after planting. R. chinensis did not show visual symptoms of Pb toxicity under lower Pb treatments; however, Pb significantly declined the growth of seedlings under higher Pb treatments. Higher Pb stress also decreased the concentrations of nitrogen in leaves, but increased the concentrations of P and K in roots. Pb stress also decreased Mn concentrations in leaves. A great quantity of Pb was uptake and mostly retained in R. chinensis roots. Nonetheless, R. chinensis can still concentrate 459.3 and 1102.7â¯mg/kg Pb in leaves and stems, respectively. Most of Pb in R. chinensis tissues was stored in the cell wall with HAc-, HCl-, and NaCl-extractable form. LMWOAs secreted by R. chinensis roots showed a strong positive correlation with Pb concentrations in all plant tissues and with P in roots. Our results suggested that Pb deposited in the cell wall and integration with phosphate or oxalate might be responsible for the tolerance of R. chinensis under Pb stress in short period.
Subject(s)
Biodegradation, Environmental , Lead/toxicity , Rhus/physiology , Soil Pollutants/toxicity , Lead/metabolism , Soil Pollutants/metabolism , Stress, PhysiologicalABSTRACT
Hyoliths are a taxonomically problematic group of Palaeozoic lophotrochozoans that are among the first shelly fossils to appear in the Cambrian period. On the basis of their distinctive exoskeleton, hyoliths have historically been classified as a separate phylum with possible affinities to the molluscs, sipunculans or lophophorates-but their precise phylogenetic position remains uncertain. Here, we describe a new orthothecide hyolith from the Chengjiang Lagerstätte (Cambrian Series 2 Stage 3), Pedunculotheca diania Sun, Zhao et Zhu gen. et sp. nov., which exhibits a non-mineralized attachment structure that strikingly resembles the brachiopod pedicle-the first report of a peduncular organ in hyoliths. This organ establishes a sessile, suspension feeding ecology for these orthothecides and-together with other characteristics (e.g. bilaterally symmetrical bivalve shell enclosing a filtration chamber and the differentiation of cardinal areas)-identifies hyoliths as stem-group brachiopods. Our phylogenetic analysis indicates that both hyoliths and crown brachiopods derived from a tommotiid grade, and that the pedicle has a single origin within the brachiopod total group.
Subject(s)
Fossils , Invertebrates/anatomy & histology , Invertebrates/classification , Animal Shells , Animals , PhylogenyABSTRACT
Patients with diabetes mellitus often develop corneal complications and delayed wound healing. How diabetes might alter acute inflammatory responses to tissue injury, leading to delayed wound healing, remains mostly elusive. Using a streptozotocin-induced type I diabetes mellitus mice and corneal epithelium-debridement wound model, we discovered that although wounding induced marked expression of IL-1ß and the secreted form of IL-1 receptor antagonist (sIL-1Ra), diabetes suppressed the expressions of sIL-1Ra but not IL-1ß in healing epithelia and both in whole cornea. In normoglycemic mice, IL-1ß or sIL-1Ra blockade delayed wound healing and influenced each other's expression. In diabetic mice, in addition to delayed reepithelization, diabetes weakened phosphatidylinositol 3-kinase-Akt signaling, caused cell apoptosis, diminished cell proliferation, suppressed neutrophil and natural killer cell infiltrations, and impaired sensory nerve reinnervation in healing mouse corneas. Local administration of recombinant IL-1Ra partially, but significantly, reversed these pathological changes in the diabetic corneas. CXCL10 was a downstream chemokine of IL-1ß-IL-1Ra, and exogenous CXCL10 alleviated delayed wound healing in the diabetic, but attenuated it in the normal corneas. In conclusion, the suppressed early innate/inflammatory responses instigated by the imbalance between IL-1ß and IL-1Ra is an underlying cause for delayed wound healing in the diabetic corneas. Local application of IL-1Ra accelerates reepithelialization and may be used to treat chronic corneal and potential skin wounds of diabetic patients.
Subject(s)
Corneal Diseases/metabolism , Diabetes Complications/metabolism , Interleukin 1 Receptor Antagonist Protein/metabolism , Interleukin-1beta/metabolism , Wound Healing/physiology , Animals , Blotting, Western , Corneal Diseases/etiology , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , Immunohistochemistry , Mice , Mice, Inbred C57BL , Microscopy, Confocal , Real-Time Polymerase Chain ReactionABSTRACT
Selecting plant species that can overcome unfavorable conditions and increase the recovery of degraded mined lands remains a challenge. A pot experiment was conducted to evaluate the feasibility of using transplanted tree seedlings for the phytoremediation of lead/zinc and copper mine tailings. One-year-old bare-root of woody species (Rhus chinensis Mill, Quercus acutissima Carruth, Liquidambar formosana Hance, Vitex trifolia Linn. var. simplicifolia Cham, Lespedeza cuneata and Amorpha fruticosa Linn) were transplanted into pots with mine tailings and tested as potential metal-tolerant plants. Seedling survival, plant growth, root trait, nutrient uptake, and metal accumulation and translocation were assessed. The six species grew in both tailings and showed different tolerance level. A. fruticosa was highly tolerant of Zn, Pb and Cu, and grew normally in both tailings. Metal concentrations were higher in the roots than in the shoots of the six species. All of the species had low bioconcentration and translocation factor values. However, R. chinensis and L. formosana had significantly higher translocation factor values for Pb (0.88) and Zn (1.78) than the other species. The nitrogen-fixing species, A. fruticosa, had the highest tolerance and biomass production, implying that it has great potential in the phytoremediation of tailing areas in southern China.
Subject(s)
Copper/metabolism , Lead/metabolism , Magnoliopsida/drug effects , Soil Pollutants/metabolism , Zinc/metabolism , Biodegradation, Environmental , China , Magnoliopsida/growth & development , Magnoliopsida/physiology , Seedlings/drug effects , Seedlings/growth & development , Seedlings/physiology , Species SpecificityABSTRACT
UNLABELLED: Osteopontin (OPN) plays a crucial role in hepatocellular carcinoma (HCC) metastasis. However, little is known about the impact of OPN polymorphisms on cancer progression. In this study, we first identified the single nucleotide polymorphisms (SNPs) in the OPN promoter region by direct sequencing in 30 HCCs, and then evaluated the prognostic values of the selected ones in two large cohorts of 826 HCC patients. The identified SNPs were functionally analyzed using in vitro and in vivo assays and their correlations with OPN levels were also evaluated. Only SNP at locus -443 and their related haplotypes (Ht2: -1748A/-616G/-443T/-155* [*indicates base deletion]; Ht3: -1748A/-616G/-443C/-155*) were significantly associated with overall survival (OS) and time to recurrence (TTR). The patients with the -443TT/TC genotype or Ht2 had a shorter OS and TTR compared with those with -443CC genotype or Ht3. This was further confirmed in the validation cohort. Moreover, this correlation remained significant in patients with small HCCs (≤5 cm). Multivariate analyses indicated that the prognostic performance of the -443 genotypes (OS, P=0.031; TTR, P=0.005) and their related haplotypes (OS, P=0.002; TTR, P=0.001) was independent of other clinicopathological factors. The Ht2 and -443TT genotype could significantly increase the promoter transcriptional activity and expression level of OPN compared with the Ht3 or -443CC genotype, and lead to an obvious increase in both in vitro invasion and in vivo tumor growth and lung metastasis of HCC cells (P<0.05). CONCLUSION: The genetic variation at locus -443 of the OPN promoter plays important roles in the regulation of OPN expression and cancer progression of HCCs, which is a novel determinant and target for HCC metastasis and prognosis.
Subject(s)
Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/secondary , Liver Neoplasms/genetics , Liver Neoplasms/pathology , Osteopontin/genetics , Female , Gene Expression Regulation, Neoplastic , Genetic Testing , Haplotypes , Humans , Male , Middle Aged , Polymorphism, Single Nucleotide/genetics , Prognosis , Promoter Regions, Genetic/geneticsABSTRACT
The Adam algorithm is a common choice for optimizing neural network models. However, its application often brings challenges, such as susceptibility to local optima, overfitting and convergence problems caused by unstable learning rate behavior. In this article, we introduce an enhanced Adam optimization algorithm that integrates Warmup and cosine annealing techniques to alleviate these challenges. By integrating preheating technology into traditional Adam algorithms, we systematically improved the learning rate during the initial training phase, effectively avoiding instability issues. In addition, we adopt a dynamic cosine annealing strategy to adaptively adjust the learning rate, improve local optimization problems and enhance the model's generalization ability. To validate the effectiveness of our proposed method, extensive experiments were conducted on various standard datasets and compared with traditional Adam and other optimization methods. Multiple comparative experiments were conducted using multiple optimization algorithms and the improved algorithm proposed in this paper on multiple datasets. On the MNIST, CIFAR10 and CIFAR100 datasets, the improved algorithm proposed in this paper achieved accuracies of 98.87%, 87.67% and 58.88%, respectively, with significant improvements compared to other algorithms. The experimental results clearly indicate that our joint enhancement of the Adam algorithm has resulted in significant improvements in model convergence speed and generalization performance. These promising results emphasize the potential of our enhanced Adam algorithm in a wide range of deep learning tasks.
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Growth differentiation factor-15 (GDF15) increases in circulation during pregnancy and has been implicated in food intake, weight loss, complications of pregnancy, and metabolic illness. We used a Gdf15 knockout mouse model (Gdf15-/- ) to assess the role of GDF15 in body weight regulation and food intake during pregnancy. We found that Gdf15-/- dams consumed a similar amount of food and gained comparable weight during the course of pregnancy compared to Gdf15+/+ dams. Insulin sensitivity on gestational day 16.5 was also similar between genotypes. In the postnatal period, litter size, and survival rates were similar between genotypes. There was a modest reduction in birth weight of Gdf15-/- pups, but this difference was no longer evident postnatal day 3.5 to 14.5. We observed no detectable differences in milk volume production or milk fat percentage. These data suggest that GDF15 is dispensable for changes in food intake, and body weight as well as insulin sensitivity during pregnancy in a mouse model.
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Developmental exposure to endocrine disruptors like bisphenol A (BPA) are implicated in later-life metabolic dysfunction. Leveraging a unique sheep model of developmental programming, we conducted an exploratory analysis of the programming effects of BPA on the endocrine pancreas. Pregnant ewes were administered environmentally relevant doses of BPA during gestational days (GD) 30-90, and pancreata from female fetuses and adult offspring were analyzed. Prenatal BPA exposure induced a trend toward decreased islet insulin staining and ß-cell count, increased glucagon staining and α-cell count, and increased α-cell/ß-cell ratio. Findings were most consistent in fetal pancreata assessed at GD90 and in adult offspring exposed to the lowest BPA dose. While not assessed in fetuses, adult islet fibrosis was increased. Collectively, these data provide further evidence that early-life BPA exposure is a likely threat to human metabolic health. Future studies should corroborate these findings and decipher the molecular mechanisms of BPA's developmental endocrine toxicity.
Subject(s)
Benzhydryl Compounds , Islets of Langerhans , Phenols , Prenatal Exposure Delayed Effects , Animals , Benzhydryl Compounds/toxicity , Female , Phenols/toxicity , Pregnancy , Sheep , Prenatal Exposure Delayed Effects/chemically induced , Prenatal Exposure Delayed Effects/pathology , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , Islets of Langerhans/pathology , Endocrine Disruptors/toxicity , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/pathology , Maternal Exposure/adverse effects , Insulin/metabolism , Fetus/drug effects , Glucagon-Secreting Cells/drug effects , Glucagon-Secreting Cells/metabolism , Glucagon-Secreting Cells/pathologyABSTRACT
The timing of food intake is a novel dietary component that impacts health. Time-restricted feeding (TRF), a form of intermittent fasting, manipulates food timing. The timing of eating may be an important factor to consider during critical periods, such as pregnancy. Nutrition during pregnancy, too, can have a lasting impact on offspring health. The timing of food intake has not been thoroughly investigated in models of pregnancy, despite evidence that interest in the practice exists. Therefore, using a mouse model, we tested body composition and glycemic health of gestational early TRF (eTRF) in male and female offspring from weaning to adulthood on a chow diet and after a high-fat, high-sucrose (HFHS) diet challenge. Body composition was similar between groups in both sexes from weaning to adulthood, with minor increases in food intake in eTRF females and slightly improved glucose tolerance in males while on a chow diet. However, after 10 weeks of HFHS, male eTRF offspring developed glucose intolerance. Further studies should assess the susceptibility of males, and apparent resilience of females, to gestational eTRF and assess mechanisms underlying these changes in adult males.
Subject(s)
Glucose Intolerance , Prenatal Exposure Delayed Effects , Pregnancy , Male , Female , Humans , Intermittent Fasting , Diet, High-Fat , Body CompositionABSTRACT
Obesity and metabolic diseases are rising among women of reproductive age, increasing offspring metabolic risk. Maternal nutritional interventions during lactation present an opportunity to modify offspring outcomes. We previously demonstrated in mice that adult male offspring have metabolic impairments and increased adipose tissue macrophages (ATM) when dams are fed high fat diet (HFD) during the postnatal lactation window (HFD PN). We sought to understand the effect of HFD during lactation on early-life inflammation. HFD PN offspring were evaluated at postnatal day 16 to 19 for tissue weight and gene expression. Profiling of adipose tissue and bone marrow immune cells was conducted through lipidomics, in vitro myeloid colony forming unit assays, and flow cytometry. HFD PN mice had more visceral gonadal white adipose tissue (GWAT) and subcutaneous fat. Adipose tissue RNA sequencing demonstrated enrichment of inflammation, chemotaxis, and fatty acid metabolism and concordant changes in GWAT lipidomics. Bone marrow (BM) of both HFD PN male and female offspring had increased monocytes (CD45+Ly6G-CD11b+CD115+) and B cells (CD45+Ly6G-CD11b-CD19+). Similarly, serum from HFD PN offspring enhanced in vitro BM myeloid colonies in a toll-like receptor 4-dependent manner. We identified that male HFD PN offspring had increased GWAT pro-inflammatory CD11c+ ATMs (CD45+CD64+). Maternal exposure to HFD alters milk lipids enhancing adiposity and myeloid inflammation even in early life. Future studies are needed to understand the mechanisms driving this pro-inflammatory state of both BM and ATMs, the causes of the sexually dimorphic phenotypes, and the feasibility of intervening in this window to improve metabolic health.
Subject(s)
Diet, High-Fat , Obesity , Female , Male , Mice , Animals , Humans , Diet, High-Fat/adverse effects , Obesity/etiology , Lactation , Inflammation , Maternal Exposure , Maternal Nutritional Physiological PhenomenaABSTRACT
Using plants to treat polluted sites and groundwater is an approach called phytoremediation. The aim of the present study was to investigated the toxicity, uptake, accumulation, and removal of 2,4-dichlorophenol (2,4-DCP) in four Salix matsudana clones and to screen the feasibility of phytoremediation using S. matsudana clones. Willows were exposed to 2,4-DCP in hydroponic solution with the concentrations of 10, 20 and 30mg L(-1) for 96h. The biomass of shoots and roots were reduced. Chlorophyll content decreased significantly compared with the control. All root morphology values were different between clones and different concentrations. The 2,4-DCP endurance of four S. matsudana clones was gauged as follows: clone 18> clone 22> clone 8> clone 10. S. matsudana was found to promote 2,4-DCP removal relative to the contaminated solution without plants. From 52.2% to 73.7% of 2,4-DCP were removed by all treatments after 96h exposure. 2,4-DCP was mainly accumulated in roots than in shoots. Clone 22 was the most efficient for the accumulation of 2,4-DCP in plant tissues. The removal of 2,4-DCP from the media may result from its degradation or polymerized in the root zone by the plant enzymes. Phytoremediation of 2,4-DCP with S. matsudana clone 8, 18 and 22 seem to be a viable option, especially at lower concentrations. These clones could remove 2,4-DCP from aquatic environment rapidly and efficiently. In addition, the toxic effect on trees during the removal process is not lethal.
Subject(s)
Chlorophenols/metabolism , Salix/metabolism , Water Pollutants, Chemical/metabolism , Biodegradation, Environmental , Chlorophyll/metabolism , Hydroponics , Plant Roots/drug effects , Plant Roots/metabolism , Salix/drug effects , Solutions/chemistry , Water Pollutants, Chemical/toxicityABSTRACT
Most current research on Alzheimer's disease (AD) is based on transverse measurements. Given the nature of neurodegeneration in AD progression, observing longitudinal changes in the structural features of brain networks over time may improve the accuracy of the predicted transformation and provide a good measure of the progression of AD. Currently, there is no cure for patients with existing AD dementia, but patients with mild cognitive impairment (MCI) in the prodromal stage of AD dementia may be diagnosed. The study of the early diagnosis of MCI and the prediction of MCI to AD transformation is of great significance for the monitoring of the MCI to AD transformation process. Despite the high rate of MCI conversion to AD, the neuropathological cause of MCI is heterogeneous. However, many people with MCI remain stable. Treatment options are different for patients with stable MCI and those with underlying dementia. Therefore, it is of great significance for clinical practice to predict whether patients with MCI will develop AD dementia. This paper proposes an improved algorithm that is based on a convolution neural network (CNN) with residuals combined with multi-layer long short-term memory (LSTM) to diagnose AD and predict MCI. Firstly, multi-time resting-state fMRI images were obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database for preprocessing, and then an AAL brain partition template was used to construct a 90 × 90 functional connectivity (FC) network matrix of a whole-brain region of interest (ROI). Secondly, the diversity of training samples was increased by generating an adversarial network (GAN). Finally, a CNN with residuals and a multi-layer LSTM model were constructed to automatically classify and predict the functional adjacency matrix. This method can not only distinguish Alzheimer's disease from normal health conditions at multiple time points, but can also predict progressive MCI (pMCI) and stable MCI (sMCI) at multiple time points. The classification accuracies in AD vs. NC and sMCI vs.pMCI reached 93.5% and 75.5%, respectively.
Subject(s)
Alzheimer Disease , Cognitive Dysfunction , Alzheimer Disease/diagnostic imaging , Brain/diagnostic imaging , Cognitive Dysfunction/diagnostic imaging , Humans , Magnetic Resonance Imaging/methods , Neural Networks, Computer , Spatial AnalysisABSTRACT
Our previous study has identified HTPAP as a novel metastasis suppressor from chromosome 8p which is often deleted in metastatic HCC. We sought to further evaluate the expression levels of transcript variants of HTPAP (HTPAP-1, HTPAP-2 and HTPAP-3) in 67 HCC tumor tissues and 11 normal liver tissues by RT-PCR with specific TaqMan probes and primer sets, and explore their association with HCC metastasis and survival. We found that the expression levels of three HTPAP transcript variants were quite different in HCCs. Only HTPAP-1 was found to be significantly associated with HCC metastasis (P=0.00053), overall survival (P=0.0023) and time to recurrence (P=0.010) of HCC. Patients with a lower expression of HTPAP-1 were inclined to accompany intrahepatic metastases and tumor thrombi (P<0.05) and had a poor prognosis. In vitro, three fusion pEGFP-N1 vectors encoding HTPAP-1, HTPAP-2 and HTPAP-3 were introduced into HCC cells respectively to track HTPAPs' expressions and identify their function. We found overexpression of HTPAP-1 conferred HCC cells reduced ability of invasion without significant impact on cell proliferation, and also displayed a distinct cell location on cell membrane and in cytoplasm, which were different from two other variants. Consequently, HTPAP-1 may be the transcript of HTPAP to exhibit a suppressive role on HCC metastasis, and can be a prognostic marker for HCC.
Subject(s)
Carcinoma, Hepatocellular/genetics , Chromosomes, Human, Pair 8 , Genes, Tumor Suppressor , Liver Neoplasms/genetics , Phosphatidate Phosphatase/genetics , Adult , Aged , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Proliferation , Down-Regulation , Female , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Middle Aged , Neoplasm Invasiveness , Neoplasm Metastasis , Prognosis , RNA, Messenger/analysis , Transcription, GeneticABSTRACT
Maternal metabolic disease and diet during pregnancy and lactation have important implications for the programming of offspring metabolic disease. In addition, high-fat diets during pregnancy and lactation can predispose the offspring to non-alcoholic fatty liver disease (NAFLD), a rising health threat in the U.S. We developed a model of maternal high-fat feeding exclusively during the lactation period. We previously showed that offspring from dams, given lactational high-fat diet (HFD), are predisposed to obesity, glucose intolerance, and inflammation. In separate experiments, we also showed that lactational metformin treatment can decrease offspring metabolic risk. The purpose of these studies was to understand the programming implications of lactational HFD on offspring metabolic liver disease risk. Dams were fed a 60% lard-based HFD from the day of delivery through the 21-day lactation period. A subset of dams was also given metformin as a co-treatment. Starting at weaning, the offspring were fed normal fat diet until 3 months of age; at which point, a subset was challenged with an additional HFD stressor. Lactational HFD led male offspring to develop hepatic insulin resistance. The post-weaning HFD challenge led male offspring to progress to NAFLD with more severe outcomes in the lactational HFD-challenged offspring. Co-administration of metformin to lactating dams on HFD partially rescued the offspring liver metabolic defects in males. Lactational HFD or post-weaning HFD had no impact on female offspring who maintained a normal insulin sensitivity and liver phenotype. These findings indicate that HFD, during the lactation period, programs the adult offspring to NAFLD risk in a sexually dimorphic manner. In addition, early life intervention with metformin via maternal exposure may prevent some of the liver programming caused by maternal HFD.
ABSTRACT
When plants encounter environmental stresses, phytohormone abscisic acid (ABA) accumulates quickly and efficiently reduces water loss by inducing stomatal closure. Reactive oxygen species (ROS) is an important regulator in ABA-induced stomatal closure, and ROS generation is modulated by multiple components in guard-cell ABA signaling. ROP interactive CRIB-containing protein 7 (RIC7) has been found to negatively regulate ABA-induced stomatal closure. However, the molecular details of the RIC7 function in this process are unclear. Here, by using two RIC7 overexpressing mutants, we confirmed the negative role of RIC7 in ABA-induced stomatal closure and found that guard cells of RIC7 overexpressing mutants generated less H2O2 than the wild type with ABA treatment, which were consistent with the reduced expression levels of ROS generation related NADPH oxidase genes AtRBOHD and AtRBOHF, and cytosolic polyamine oxidase genes PAO1 and PAO5 in the RIC7 overexpressing mutants. Furthermore, external applied H2O2 failed to rescue the defects of stomatal closure in RIC7 overexpressing mutants. These results suggest that RIC7 affects H2O2 generation in guard cells, and the function of H2O2 is dependent on RIC7 in ABA-induced stomatal closure, indicative of interdependency between RIC7 and H2O2 in ABA guard-cell signaling.