Search

Remote sensing Change Detection (CD) involves identifying changing regions of interest in bi-temporal remote sensing images. CD technology has rapidly developed in recent years through the powerful learning ability of Convolutional Neural Networks (CNN), affording complex feature extraction. However, the local receptive fields in the CNN limit modeling long-range contextual relationships in semantic changes. Therefore, this work explores the great potential of Siamese Transformers in CD tasks and proposes a general CD model entitled STCD that relies on Swin Transformers. In the encoding process, pure Transformers without CNN are used to model the long-range context of semantic tokens, reducing computational overhead and improving model efficiency compared to current methods. During the decoding process, the 3D convolution block obtains the changing features in the time series and generates the predicted change map in the deconvolution layer with axial attention. Extensive experiments on three binary CD datasets and one semantic CD dataset demonstrate that the proposed STCD model outperforms several popular benchmark methods considering performance and the required parameters. Among the STCD variants, the F1-Score of the Base-STCD on the three binary CD datasets LEVIR, DSIFN, and SVCD reached 89.85%, 54.72%, and 93.75%, respectively, and the mF1-Score and mIoU on the semantic CD dataset SECOND were 75.60% and 66.19%.

To extend the post-harvest storage duration of peppermint and predict the post-harvest respiration rate of peppermint, peppermint was subjected to modified atmosphere packaging conditions with different packaging materials (PE, OPP1.8/PE3.5, OPP1.8/4.5, OPP2.3/PE4.5, HDPE), various O2 concentrations (3%~7%), and different CO2 concentrations (5%~15%). Parameters including weight loss rate, relative electrical conductivity, color difference, sensory evaluation, vitamin C content, total chlorophyll content, and total colony count were measured. Response surface optimization experiments were conducted with O2, CO2, and packaging materials as factors to determine the optimal gas ratios and packaging materials for post-harvest preservation of peppermint. On this basis, the volatile compounds and surface fungal diversity of peppermint were studied. The proportions of O2 and CO2 inside the optimal packaging materials for peppermint were measured by using the closed space system. Based on this, a model equation was obtained using the permeation system method and numerically simulated. Matlab software was used to calculate the respiration rate at equilibrium, and a regression analysis was performed using a quadratic polynomial model. High-throughput sequencing was used to sequence and analyze peppermint samples from the optimal, worst, and control treatment groups, comparing changes in the proportion of dominant microbial communities. The results showed that the optimal gas composition and packaging material were 3.5% O2+9.4% CO2 and HDPE, which extended the freshness period of peppermint from 7~9 days to 10~12 days. It could inhibit the increase of linalool and other alcohols during peppermint storage, reduce the volatilization of D-carvone and other ketones, and delay the senescence of peppermint. Based on these experiments, a more accurate quadratic respiration rate model for peppermint under controlled atmosphere packaging was established, which effectively inhibited the growth of decay-causing microorganisms such as Ascomycota and Mycetes in peppermint.

Summary: Orofacial clefts (OFCs) are common congenital birth defects with various etiologies, including genetic variants. Online Mendelian Inheritance in Man (OMIM) annotated several hundred genes involving OFCs. Furthermore, several hundreds of de novo variants (DNVs) have been identified from individuals with OFCs. Some DNVs are related to known OFC genes or pathways, but there are still many DNVs whose relevance to OFC development is unknown. To explore novel gene functions and their cellular expression profiles, we focused on DNVs in genes that were not listed in OMIM. We collected 960 DNVs in 853 genes from published studies and curated these genes, based on the DNVs’ deleteriousness, into 230 and 23 genes related to cleft lip with or without cleft palate (CL/P) and cleft palate only (CPO), respectively. For comparison, we curated 178 CL/P and 277 CPO genes from OMIM. In CL/P, the pathways enriched in DNV and OMIM genes were significantly overlapped (p = 0.002). Single-cell RNA sequencing (scRNA-seq) analysis of mouse lip development revealed that both gene sets had abundant expression in the ectoderm (DNV genes: adjusted p = 0.032, OMIM genes: adjusted p

Strawberry (Fragaria × ananassa) is a worldwide cultivated horticultural crop, however, its short preservative life of the harvested fruit remains a challenge to be addressed. Currently, although much progress has been made toward understanding the senescence of harvested strawberry fruit, the defined mechanisms remain unclear. Therefore, we performed a series of morphological, physiological and biochemical, as well as transcriptome and proteome analyses using the widely-cultivated strawberry 'Benihoppe' during 0−8 d at room temperature. The results showed not only the shorter storage of harvested strawberry fruit resulted from the rapid perishability, softening, and water loss, but also an increase in soluble sugars within 2 d and a coordination of ABA with JA at the early stage, BR at the middle stage and ethylene at the later stage, respectively. The RNA-seq data highlighted on ABA with NCEDs and PYLs, auxin with IAAs and AUXs, ethylene with ACSs, EIN3 and ERFs, BR with BZRs, and JA with JMTs; while proteome data highlighted on ABA with PYL/SnRK2/ABF, JA with JAR1/JAZ, GA with GID1, BR with BSK, and ethylene with ETR/CTR/EIN2, suggesting an important role of ABA, JA, and ethylene in the senescence of harvested strawberries. Interestingly, higher contents of nerolidalyl caproate and threonine represented characteristic signs of ripening and senescence. Finally, a physiological, molecular and metabolic model for strawberry fruit senescence is proposed, providing comprehensive insights into the preservative mechanisms.

In this study, the influence of fasting on hepatic glucose and lipid metabolism was explored by examining biochemical, antioxidative, and morphological indicators and transcriptional expression in the liver of javelin goby (Synechogobius hasta) after 0, 3, 7, or 14 days of starvation. Marked reductions in hepatic glycogen and triglycerides occurred from the seventh day of starvation until the end of the trial (p < 0.05). However, no alterations in hepatic cholesterol or protein were detected throughout the entire experiment (p > 0.05). During fasting, the activities of pyruvate kinase, lactate dehydrogenase, and glycogen phosphorylase a all rose firstly and then fell (p < 0.05). The activities of hepatic fatty acid synthase and acetyl-CoA carboxylase were minimized to their lowest levels at the end of food deprivation (p < 0.05), while lipase was elevated after 7–14 days of fasting (p < 0.05). Catalase, glutathione, and the total antioxidative capacity were increased and maintained their higher values in the later stage of fasting (p < 0.05), whereas malondialdehyde was not significantly changed (p > 0.05). Hepatic vein congestion, remarkable cytoplasmic vacuoles, and irregular cell shape were present in S. hasta which endured 3–7 days of fasting and were less pronounced when food shortage was prolonged. In terms of genes associated with glucose and lipid metabolism, the hepatic phosphofructokinase gene was constantly up-regulated during fasting (p < 0.05). However, the mRNA levels of glycogen synthase and glucose-6-phosphatase were obviously lower when the food scarcity extended to 7 days or more (p < 0.05). Fatty acid synthase, stearoyl-CoA desaturase 1, and peroxisome proliferator-activated receptor γ were substantially down-regulated in S. hasta livers after 7–14 days of food deprivation (p < 0.05). However, genes involved in lipolysis and fatty acid transport were transcriptionally enhanced to varying extents and peaked at the end of fasting (p < 0.05). Overall, starvation lasting 7 days or more could concurrently mobilize hepatic carbohydrates and fat as energy resources and diminished their hepatic accumulation by suppressing biosynthesis and enhancing catabolism and transport, ultimately metabolically and structurally perturbing the liver in S. hasta. This work presents preliminary data on the dynamic characteristics of hepatic glucose and lipid metabolism in S. hasta in response to starvation, which may shed light on the sophisticated mechanisms of energetic homeostasis in fish facing nutrient unavailability and may benefit the utilization/conservation of S. hasta.

Background: Everolimus is an inhibitor of the mammalian target of rapamycin and is used to treat various tumors. The presented study aimed to evaluate the Everolimus-associated adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS).Methods: The AE records were selected by searching the FDA Adverse Event Reporting System database from the first quarter of 2009 to the first quarter of 2022. Potential adverse event signals were mined using the disproportionality analysis, including reporting odds ratio the proportional reporting ratio the Bayesian confidence propagation neural network and the empirical Bayes geometric mean and MedDRA was used to systematically classify the results.Results: A total of 24,575 AE reports of Everolimus were obtained using data from the FAERS database, and Everolimus-induced AEs occurrence targeted 24 system organ classes after conforming to the four algorithms simultaneously. The common significant SOCs were identified, included benign, malignant and unspecified neoplasms, reproductive system and breast disorders, etc. The significant AEs were then mapped to preferred terms such as stomatitis, pneumonitis and impaired insulin secretion, which have emerged in the study usually reported in patients with Everolimus. Of note, unexpected significant AEs, including biliary ischaemia, angiofibroma, and tuberous sclerosis complex were uncovered in the label.Conclusion: This study provided novel insights into the monitoring, surveillance, and management of adverse drug reaction associated with Everolimus. The outcome of serious adverse events and the corresponding detection signals, as well as the unexpected significant adverse events signals are worthy of attention in order to improving clinical medication safety during treatment of Everolimus.

Soybean oil (SO), an important plant-derived lipid, is routinely used in aquafeed as a partial substitute for fish oil. However, the effect of various contents of SO in a SO-based aquafeed on specific aquatic animals and the underlying mechanisms are unclear. In this study, five isonitrogenous diets containing different SO contents (0 %, 3 %, 6 %, 9 %, and 12 %, named as S0, S3, S6, S9, and S12, respectively) were prepared with SO as the predominant lipid source, and 12-week feeding experiments were conducted on juvenile grass carp (Ctenopharyngodon idella) (initial weight: 12.54 ± 0.08 g). Apart from lower feed conversion ratio in the S6 and S9 groups (P 0.05). The S12 group exhibited significant decrease in the final weight and weight gain rate and increase in the viscerosomatic index (P

Abstract A growing body of evidence suggests that dysbiosis of the human gut microbiota is associated with neurodegenerative diseases like Alzheimer’s disease (AD) via neuroinflammatory processes across the microbiota-gut-brain axis. The gut microbiota affects brain health through the secretion of toxins and short-chain fatty acids, which modulates gut permeability and numerous immune functions. Observational studies indicate that AD patients have reduced microbiome diversity, which could contribute to the pathogenesis of the disease. Uncovering the genetic basis of microbial abundance and its effect on AD could suggest lifestyle changes that may reduce an individual’s risk for the disease. Using the largest genome-wide association study of gut microbiota genera from the MiBioGen consortium, we used polygenic risk score (PRS) analyses with the “best-fit” model implemented in PRSice-2 and determined the genetic correlation between 119 genera and AD in a discovery sample (ADc12 case/control: 1278/1293). To confirm the results from the discovery sample, we next repeated the PRS analysis in a replication sample (GenADA case/control: 799/778) and then performed a meta-analysis with the PRS results from both samples. Finally, we conducted a linear regression analysis to assess the correlation between the PRSs for the significant genera and the APOE genotypes. In the discovery sample, 20 gut microbiota genera were initially identified as genetically associated with AD case/control status. Of these 20, three genera (Eubacterium fissicatena as a protective factor, Collinsella, and Veillonella as a risk factor) were independently significant in the replication sample. Meta-analysis with discovery and replication samples confirmed that ten genera had a significant correlation with AD, four of which were significantly associated with the APOE rs429358 risk allele in a direction consistent with their protective/risk designation in AD association. Notably, the proinflammatory genus Collinsella, identified as a risk factor for AD, was positively correlated with the APOE rs429358 risk allele in both samples. Overall, the host genetic factors influencing the abundance of ten genera are significantly associated with AD, suggesting that these genera may serve as biomarkers and targets for AD treatment and intervention. Our results highlight that proinflammatory gut microbiota might promote AD development through interaction with APOE. Larger datasets and functional studies are required to understand their causal relationships.

Alzheimer’s Disease (AD) is a complex disease and the leading cause of dementia in older people. We aimed to uncover aspects of AD’s pathogenesis that may contribute to drug repurposing efforts by integrating DNA methylation and genetic data. Implementing the network-based tool, a dense module search of genome-wide association studies (dmGWAS), we integrated a large-scale GWAS dataset with DNA methylation data to identify gene network modules associated with AD. Our analysis yielded 286 significant gene network modules. Notably, the foremost module included the BIN1 gene, showing the largest GWAS signal, and the GNAS gene, the most significantly hypermethylated. We conducted Web-based Cell-type-Specific Enrichment Analysis (WebCSEA) on genes within the top 10% of dmGWAS modules, highlighting monocyte as the most significant cell type (p < 5 × 10−12). Functional enrichment analysis revealed Gene Ontology Biological Process terms relevant to AD pathology (adjusted p < 0.05). Additionally, drug target enrichment identified five FDA-approved targets (p-value = 0.03) for further research. In summary, dmGWAS integration of genetic and epigenetic signals unveiled new gene interactions related to AD, offering promising avenues for future studies.

The change detection (CD) of heterogeneous remote sensing images is an important but challenging task. The difficulty is to obtain the change information by directly comparing the different statistical characteristics of the images acquired by different sensors. This paper proposes an unsupervised method for heterogeneous image CD based on an image domain transfer network. First, an attention mechanism is added to the Cycle-generative adversarial networks (Cycle-GANs) to obtain a more consistent feature expression by transferring bi-temporal heterogeneous images to the common domain. The Euclidean distance of the corresponding pixels is calculated in the common domain to form a difference map, and a threshold algorithm is applied to get a rough change map. Finally, the proposed adaptive Discrete Cosine Transform (DCT) algorithm reduces the noise introduced by false detection, and the final change map is obtained. The proposed method is verified on three real heterogeneous CD datasets and compared with the current state-of-the-art methods. The results show that the proposed method is accurate and robust for performing heterogeneous CD tasks.

Triple negative breast cancers (TNBCs) are tumors with a poor treatment response and prognosis. In this study, we propose a new approach, candidate extraction from convolutional neural network (CNN) elements (CECE), for discovery of biomarkers for TNBCs. We used the GSE96058 and GSE81538 datasets to build a CNN model to classify TNBCs and non-TNBCs and used the model to make TNBC predictions for two additional datasets, the cancer genome atlas (TCGA) breast cancer RNA sequencing data and the data from Fudan University Shanghai Cancer Center (FUSCC). Using correctly predicted TNBCs from the GSE96058 and TCGA datasets, we calculated saliency maps for these subjects and extracted the genes that the CNN model used to separate TNBCs from non-TNBCs. Among the TNBC signature patterns that the CNN models learned from the training data, we found a set of 21 genes that can classify TNBCs into two major classes, or CECE subtypes, with distinct overall survival rates (P = 0.0074). We replicated this subtype classification in the FUSCC dataset using the same 21 genes, and the two subtypes had similar differential overall survival rates (P = 0.0490). When all TNBCs were combined from the 3 datasets, the CECE II subtype had a hazard ratio of 1.94 (95% CI, 1.25–3.01; P = 0.0032). The results demonstrate that the spatial patterns learned by the CNN models can be utilized to discover interacting biomarkers otherwise unlikely to be identified by traditional approaches.

Aeromonas hydrophila is a kind of zoonotic pathogen, which can cause bacterial septicemia in fish and bring huge economic losses to global aquaculture. Outer membrane proteins (Omps) are conserved antigens of Aeromonas hydrophila, which can be developed as subunit vaccines. To evaluate the protective efficacy of inactivated vaccine and recombinant outer membrane protein A (OmpA) subunit vaccine against A. hydrophila in juvenile Megalobrama amblycephala, the present study investigated the immunogenicity and protective effects of both vaccines, as well as the non-specific and specific immune response of M. amblycephala. Compared with the non-vaccinated group, both inactivated and OmpA subunit vaccines improved the survival rate of M. amblycephala upon infection. The protective effects of OmpA vaccine groups were better than that of the inactivated vaccine groups, which should be attributed to the reduced bacterial load and enhanced host immunity in the vaccinated fish. ELISA assay showed that the titer of serum immunoglobulin M (IgM) specific to A. hydrophila up-regulated significantly in the OmpA subunit vaccine groups at 14 d post infection (dpi), which should contribute to better immune protective effects. In addition, vaccination enhanced host bactericidal abilities might also attribute to the regulation of the activities of hepatic and serum antimicrobial enzymes. Moreover, the expression of immune-related genes (SAA, iNOS, IL-1 β, IL-6, IL-10, TNF α, C3, MHC I, MHC II, CD4, CD8, TCR α, IgM, IgD and IgZ) increased in all groups post infection, which was more significant in the vaccinated groups. Furthermore, the number of immunopositive cells exhibiting different epitopes (CD8, IgM, IgD and IgZ) that were detected by immunohistochemical assay had increased in the vaccinated groups post infection. These results show that vaccination effectively stimulated host immune response (especially OmpA vaccine groups). In conclusion, these results indicated that both the inactivated vaccine and OmpA subunit vaccine could protect juvenile M. amblycephala against A. hydrophila infection, of which OmpA subunit vaccine provided more effective immune protection and can be used as an ideal candidate for the A. hydrophila vaccine.

Fucoidan and laminarin are polymolecular compounds that extracted from seaweed. As functional polysaccharides, they possess various biological functions such as immunomodulatory, anti-inflammatory, antiviral and antioxidant bioactivities. Fucoidan and laminarin modulate host immune responses by activating immune cells (macrophages, neutrophils, T lymphocytes) and inducing the expression of cytokines (TNFα, IL-1β, IL-6, IL-8, NF-κB). Intelectin is a novel lectin that plays important roles in bacterial agglutination and bactericidal effects by recognizing the polysaccharide components on the cell surface of pathogens, which can also enhance the phagocytosis of macrophages. The present study intends to explore the immunomodulatory effects of fucoidan, laminarin and intelectin on the macrophages of Megalobrama amblycephala. The results showed that the incubation of both fucoidan and laminarin at the concentration of 100 μg/mL for 4 h could enhance the phagocytic capacity of M. amblycephala macrophages, which also showed remodeled cytoskeleton with extended pseudopodia. In addition, fucoidan and laminarin could induce the expression of M. amblycephala intelectin (MaINTL) in the primary hepatocytes and macrophages, and the recombinant MaINTL (rMaINTL) could bind with fucoidan and laminarin. Furthermore, fucoidan and laminarin induced the expression of cytoskeletal remodeling related genes in the primary M. amblycephala macrophages, such as Rac1 and WASP, which should contribute to the enhancement of seaweed polysaccharides (fucoidan and laminarin) and MaINTL on the phagocytosis of M. amblycephala macrophages. However, even though fucoidan and laminarin could induced the expression of CXCL8, while the chemotaxis of M. amblycephala macrophages on neutrophils was not affected by them. These findings suggested that fucoidan and laminarin enhanced the phagocytic capacity of M. amblycephala macrophages via activation of MaINTL and up-regulation of the expression of downstream cytoskeletal remodeling related genes Rac1 and WASP. Therefore, fucoidan and laminarin could be used as immune enhancers to improve host immunity and disease resistance in M. amblycephala, which provided novel insights into the prevention and protection of fish bacterial diseases.

Chlorantraniliprole (CAP) is an insecticide with low toxicity and high efficiency, which is widely used in agriculture in China. However, its potential ecological risks remain unknown. In this study, we investigated the impact of different CAP concentrations on bacterial and fungal communities in soil based on high-throughput sequencing. The results showed that CAP application had no significant effect on soil bacterial and fungal diversity, but altered the bacterial and fungal community structure. In particular, the soil bacterial and fungal community structure in the low CAP concentration treatment group exhibited large variability. Compared with 0 day, the phylum level of bacteria changed at 115 days, and fungi changed at 175 days, indicating that soil microbial community might have significant correlation with CAP degradation in soil. Correlation analysis between soil properties and microbial communities showed that TN, TP, and NO3–N were three key factors that significantly influenced microbial community structure. These results provide basic data for studying the effects of pesticides on ecosystem and potential remediation strategies of polluted soil.

In this study, the ultrasound-assisted extraction conditions of total flavonoids were optimized, and the structure and composition of total flavonoids were further analyzed. On the basis of single factor experiments, orthogonal experiments was carried out on four factors, including solid-liquid ratio, extraction time, temperature and power to obtain the optimal extraction conditions based on extraction yield. Under these conditions, total flavonoids were purified by D101 macroporous resin. The structure of total flavonoids before and after purification was characterized by UV-Vis and Fourier transform infrared spectroscopy (FT-IR). Finally, the constituents of the purified compounds were analyzed by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The results showed that the optimal extraction conditions were as follows: Ethanol concentration of 60%, solid-liquid ratio of 1:25 mg/mL, ultrasonic temperature of 45 ℃, time of 120 min, power of 250 W, and extraction yield of 2.776%. The characteristic structure of total flavonoids was analyzed by UV-Vis spectroscopy (UV-Vis). Fourier transform infrared spectroscopy (FT-IR) also showed that the total flavonoids contained O-H, C-H, C=O, C=C, phenolic hydroxyl groups and other characteristic functional groups, which was consistent with the typical structure of flavonoids. Thirty flavonoids were detected in the purified products by UPLC-MS/MS, including citrinin, hesperetin, azalea, protocatechualdehyde, diosmin, naringin chalcone, sweet orange flavone, naringin and rutin. The relative content of citrinin was the highest, which was 50.854%±0.089% . This study would provide a theoretical basis for the functional development and utilization of crystal Mesembryanthemum crystallinum.

Land-use scene classification (LUSC) is a key technique in the field of remote sensing imagery (RSI) interpretation. A convolutional neural network (CNN) is widely used for its ability to autonomously and efficiently extract deep semantic feature maps (DSFMs) from large-scale RSI data. However, CNNs cannot accurately extract the rich spatial structure information of RSI, and the key information of RSI is easily lost due to many pooling layers, so it is difficult to ensure the information integrity of the spatial structure feature maps (SSFMs) and DSFMs of RSI with CNNs only for LUSC, which can easily affect the classification performance. To fully utilize the SSFMs and make up for the insufficiency of CNN in capturing the relationship information between the land-use objects of RSI, while reducing the loss of important information, we propose an effective dual-branch hybrid framework, HFCC-Net, for the LUSC task. The CNN in the upper branch extracts multi-scale DSFMs of the same scene using transfer learning techniques; the graph routing-based CapsNet in the lower branch is used to obtain SSFMs from DSFMs in different scales, and element-by-element summation achieves enhanced representations of SSFMs; a newly designed function is used to fuse the top-level DSFMs with SSFMs to generate discriminant feature maps (DFMs); and, finally, the DFMs are fed into classifier. We conducted sufficient experiments using HFCC-Net on four public datasets. The results show that our method has better classification performance compared to some existing CNN-based state-of-the-art methods.

This study aimed to explore the effects of different starch source diets on the growth performance and hepatopancreas RNA-seq of grass carp. Juvenile grass carp (initial body weight of 39.4 ± 1.6 g) were fed diets containing 25% corn (CO), potato (PO), and wheat (WH) starch for 8 weeks, respectively. The weight gain ratio (WGR) was significantly lower, whereas the visceral somatic index (VSI) and feed conversion ratio (FCR) were significantly higher in the CO group than those in the PO and WH groups. These indicators did not significantly differ between the PO and WH groups. Hepatopancreas RNA-seq analysis showed that 536, 514, and 647 differentially expressed genes (DEGs) were screened out in the comparisons of PO vs. WH, PO vs. CO, and CO vs. WH. The DEGs were mainly enriched in the several known pathways involved in steroid biosynthesis, cell cycle, fatty acid metabolism, and fat digestion and absorption according to Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis. The major DEGs related to lipid and carbohydrate metabolism were analyzed, in which lipogenesis-related DEGs (fasn, acc1, scd1, elovl6, and me1), fat digestion and absorption-related DEGs (fabp7, apoa1, apoa4, and pla2), and glycometabolism-related DEGs (gk, g6pd, and pepck) were down-regulated in the PO group compared with those in the CO and WH groups. Conversely, steroid synthesis-related DEGs (hmgcs, fdft1, sqle, lss, cyp51, msmo1, nsdhl, ugt, cyp1b1, and cyp7a1) were up-regulated in the PO group. These results indicate that the long-term PO ingestion could modulate hepatic lipid metabolism by reducing fatty acid biosynthesis and increasing bile acid biosynthesis. PO may be healthier in contrast to CO alone, which may not be suitable as a starch source in grass carp diet.

Remote sensing scene objective recognition (RSSOR) plays a serious application value in both military and civilian fields. Convolutional neural networks (CNNs) have greatly enhanced the improvement of intelligent objective recognition technology for remote sensing scenes, but most of the methods using CNN for high-resolution RSSOR either use only the feature map of the last layer or directly fuse the feature maps from various layers in the “summation” way, which not only ignores the favorable relationship information between adjacent layers but also leads to redundancy and loss of feature map, which hinders the improvement of recognition accuracy. In this study, a contextual, relational attention-based recognition network (CRABR-Net) was presented, which extracts different convolutional feature maps from CNN, focuses important feature content by using a simple, parameter-free attention module (SimAM), fuses the adjacent feature maps by using the complementary relationship feature map calculation, improves the feature learning ability by using the enhanced relationship feature map calculation, and finally uses the concatenated feature maps from different layers for RSSOR. Experimental results show that CRABR-Net exploits the relationship between the different CNN layers to improve recognition performance, achieves better results compared to several state-of-the-art algorithms, and the average accuracy on AID, UC-Merced, and RSSCN7 can be up to 96.46%, 99.20%, and 95.43% with generic training ratios.

Abstract Background Transcriptome sequencing has been broadly available in clinical studies. However, it remains a challenge to utilize these data effectively for clinical applications due to the high dimension of the data and the highly correlated expression between individual genes. Methods We proposed a method to transform RNA sequencing data into artificial image objects (AIOs) and applied convolutional neural network (CNN) algorithms to classify these AIOs. With the AIO technique, we considered each gene as a pixel in an image and its expression level as pixel intensity. Using the GSE96058 (n = 2976), GSE81538 (n = 405), and GSE163882 (n = 222) datasets, we created AIOs for the subjects and designed CNN models to classify biomarker Ki67 and Nottingham histologic grade (NHG). Results With fivefold cross-validation, we accomplished a classification accuracy and AUC of 0.821 ± 0.023 and 0.891 ± 0.021 for Ki67 status. For NHG, the weighted average of categorical accuracy was 0.820 ± 0.012, and the weighted average of AUC was 0.931 ± 0.006. With GSE96058 as training data and GSE81538 as testing data, the accuracy and AUC for Ki67 were 0.826 ± 0.037 and 0.883 ± 0.016, and that for NHG were 0.764 ± 0.052 and 0.882 ± 0.012, respectively. These results were 10% better than the results reported in the original studies. For Ki67, the calls generated from our models had a better power for prediction of survival as compared to the calls from trained pathologists in survival analyses. Conclusions We demonstrated that RNA sequencing data could be transformed into AIOs and be used to classify Ki67 status and NHG with CNN algorithms. The AIO method could handle high-dimensional data with highly correlated variables, and there was no need for variable selection. With the AIO technique, a data-driven, consistent, and automation-ready model could be developed to classify biomarkers with RNA sequencing data and provide more efficient care for cancer patients.

This study identified the constituents of purified flavonoid (PEF) isolated from Mesembryanthemum crystallinum and examined their inhibitory effects on low-density lipoprotein (LDL) oxidation and non-enzymatic glycosylation. More than 30 kinds of flavonoid compounds were identified in M. crystallinum, including tangeretin, nobiletin, farrerol, protocatechuic aldehyde, diosmin, and rutin. Moreover, tangeretin corresponds to approximately 51% of the total identified flavonoids. PEF had a low IC50 value for 1,1-diphenyl-2-picrylhydrazyl radicals (DPPH·), hydroxyl radical (·OH), and superoxide anion free radical (O2-·) scavenging. They were found to effectively delay and inhibit the production of conjugated diene (CD) and thiobarbituric acid reactive substance (TBARS) during LDL oxidation. Meanwhile, scanning electron microscopy (SEM) of the LDL oxidation incubation system with PEF showed a smooth and dense surface, with no obvious cavitation phenomenon. Furthermore, PEF effectively inhibited the production of LDL glycosylation products and showed a strong inhibitory effect in the latter stage. The electrophoresis of advanced glycosylation end products (AGEs) further confirmed that PEF can effectively prevent the cross-linking between glucose and proteins, protecting LDL from glycosylation-induced damage.

The threat of bacterial septicemia caused by Aeromonas hydrophila infection to aquaculture growth can be prevented through vaccination, but differences among A. hydrophila strains may affect the effectiveness of non-conserved subunit vaccines or non-inactivated A. hydrophila vaccines, making the identification and development of conserved antigens crucial. In this study, a bioinformatics analysis of 4268 protein sequences encoded by the A. hydrophila J-1 strain whole genome was performed based on reverse vaccinology. The specific analysis included signal peptide prediction, transmembrane helical structure prediction, subcellular localization prediction, and antigenicity and adhesion evaluation, as well as interspecific and intraspecific homology comparison, thereby screening the 39 conserved proteins as candidate antigens for A. hydrophila vaccine. The 9 isolated A. hydrophila strains from diseased fish were categorized into 6 different molecular subtypes via enterobacterial repetitive intergenic consensus (ERIC)-PCR technology, and the coding regions of 39 identified candidate proteins were amplified via PCR and sequenced to verify their conservation in different subtypes of A. hydrophila and other Aeromonas species. In this way, conserved proteins were screened out according to the comparison results. Briefly, 16 proteins were highly conserved in different A. hydrophila subtypes, of which 2 proteins were highly conserved in Aeromonas species, which could be selected as candidate antigens for vaccines development, including type IV pilus secretin PilQ (AJE35401.1) and TolC family outer membrane protein (AJE35877.1). The present study screened the conserved antigens of A. hydrophila by using reverse vaccinology, which provided basic foundations for developing broad-spectrum protective vaccines of A. hydrophila.

Mannan oligosaccharides (MOS) have been studied and applied as a feed additive, whereas their regulation on the growth performance and immunity of aquatic animals lacks consensus. Furthermore, their immunoprotective effects on the freshwater fish Megalobrama amblycephala have not been sufficiently studied. Thus, we investigated the effects of dietary MOS of 0, 200, and 400 mg/kg on the growth performance, non-specific immunity, intestinal health, and resistance to Aeromonas hydrophila infection in juvenile M. amblycephala. The results showed that the weight gain rate of juvenile M. amblycephala was not significantly different after 8 weeks of feeding, whereas the feed conversion ratio decreased in the MOS group of 400 mg/kg. Moreover, dietary MOS increased the survival rate of juvenile M. amblycephala upon infection, which may be attributed to enhanced host immunity. For instance, dietary MOS increase host bactericidal and antioxidative abilities by regulating the activities of hepatic antimicrobial and antioxidant enzymes. In addition, MOS supplementation increased the number of intestinal goblet cells, and the intestine was protected from necrosis of the intestinal folds and disruption of the microvilli and junctional complexes, thus maintaining the stability of the intestinal epithelial barrier. The expression levels of M. amblycephala immune and tight junction-related genes increased after feeding dietary MOS for 8 weeks. However, the upregulated expression of immune and tight junction-related genes in the MOS supplemental groups was not as notable as that in the control group postinfection. Therefore, MOS supplementation might suppress the damage caused by excessive intestinal inflammation. Furthermore, dietary MOS affected the richness and composition of the gut microbiota, which improved the gut health of juvenile M. amblycephala by increasing the relative abundance of beneficial gut microbiota. Briefly, dietary MOS exhibited significant immune protective effects to juvenile M. amblycephala, which is a functional feed additive and immunostimulant.

As the basis of stereo observation, epipolar resampling is a critical technology for 3D reconstruction. With the development of the 3D reconstruction using multi-view satellite images, the epipolar resampling of the multi-view satellite images has become a new challenging problem. In this paper, we propose an epipolar resampling method for multi-view high resolution satellite images based on block. Firstly, we establish the relationship between the vertical parallax and image block size for the epipolar resampling based on block. Using this relationship, we can choose the block size to limit the maximum vertical parallax in epipolar resampling. Secondly, we use the rational function model (RFM) to generate virtual corresponding points for fundamental matrix estimation, so image pairs with large stereo angles and poor consistency in multi-view satellite images which are difficult to extract feature matching point can be rectified. Experiments with multi-view satellite images demonstrated the universality and effectiveness of the proposed method. All the image pairs in the multi-view satellite image dataset were rectified successfully. The average epipolar resampling error is only 0.25 pixels when we rectify the multi-view satellite images acquired by WorldView-3 with the block size of 3000*3000 pixels, significantly less than the similar method.

Lipid was an essential constituent of aquatic feeds, among which fish oil (FO) was the most excellent lipid source for its nutritive values. However, high price and limited production restricted its application, thus leading to the consideration of developing other alternative lipid sources, and soybean oil (SO) instead of FO was applied as the main lipid source in the commercial feed of grass carp. In the present study, two typical lipids sources FO and SO were used to prepare grass carp feed, and their comparative effects on the growth performance, nutrient composition and metabolic signaling were investigated. The growth performance of two groups exhibited no significant difference, while crude lipid was much higher in the muscle of SO group. Additionally, muscle fatty acid composition of both groups were highly correlated with that of diets, and the proportion of muscle n-3 polyunsaturated fatty acids was notably higher in the FO group, especially that of C20:5n-3 (EPA) and C22:6n-3 (DHA). Comparative digital gene expression profiles (DGE) was conducted and 1261 differentially expressed genes (DEGs) had been identified, then gene ontology (GO) enrichment analysis revealed the enriched functional subterms were primarily focused on cellular metabolic processes and regulation. KEGG pathway analysis elucidated the main metabolism related pathways, and DEGs involved in fatty acid elongation, fatty acid metabolism, and glycerolipid metabolism pathways were listed, including elongation of very long chain fatty acids protein 7 (el7), lysophospholipid acyltransferase 4 (lpcat4), long-chain acyl-CoA synthetase (acs), phosphatidate phosphatase LPIN (lpin), cathepsin L, and glucose-6-phosphate isomerase (gpi) et al. In conclusion, the nutritional composition rather than growth performance of grass carp was affected by different lipid sources, and the underlying regulatory signaling was predicted, which would provide theoretical basis for fish diet formulation.

Epipolarity is the foundation of epipolar resampling, which is used to eliminate the vertical disparity between stereo pairs in stereo matching. To analyze the epipolarity of pushbroom satellite images, this paper compares three methods based on the rational function model (RFM): the projection trajectory method (PTM), the piecewise projection trajectory method (PPTM) and our extended projection trajectory method (EPTM). To evaluate the quality of epipolar curves, we defined the deviation coefficient as a metric to evaluate the bending degree of epipolar curves. We also defined the maximum deviation coefficient of an image that can be used to determinate the tile size in multiview satellite image 3D reconstruction based on image dividing. Comparison experiments have been carried out with pushbroom satellite images using these three methods. Experimental results show that our EPTM is more convenient and practical. It only needs the forward form of the RFM to analyze the epipolarity and can be used in the epipolarity analysis of a single image. By projecting straight lines in the ground space into the image space, the EPTM can be used to perform comprehensive epipolarity analysis for pushbroom satellite images. In addition, the EPTM can be used to calculate the maximum deviation coefficient of an image that the PTM and the PPTM cannot calculate, which is important in 3D reconstruction using multiview satellite images.

Fish in natural and cultivated environments can be challenged by starvation. However, inducing starvation in a controlled manner cannot only reduce feed consumption but also reduces aquatic eutrophication and even improves farmed fish quality. This study investigated the effects of starvation on the muscular function, morphology, and regulatory signaling in javelin goby (Synechogobius hasta) by evaluating the biochemical, histological, antioxidant, and transcriptional changes in the musculature of S. hasta subjected to 3, 7, and 14 days fasting. The muscle glycogen and triglyceride levels in S. hasta were gradually reduced under starvation, reaching their lowest at the end of the trial (P

Mannan oligosaccharides (MOS) are functional oligosaccharides with beneficial effects on the non-specific immunity of Megalobrama amblycephala, but systematic studies on the immunomodulatory mechanisms of MOS are still lacking. To investigate the protective mechanisms of three different levels of dietary MOS supplementation on the intestinal immunity of juvenile M. amblycephala, comparative digital gene expression (DGE) profiling was performed. In this study, 622 differentially expressed genes (DEGs) were identified, while the similar expression tendency of 34 genes by qRT-PCR validated the accuracy of the DGE analyses. Gene Ontology (GO) enrichment revealed that the DEGs were mainly enriched in two functional categories of biological process and molecular function. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that the DEGs were mainly related to complement and coagulation cascades, coagulation cascades, platelet activation, natural killer cell mediated cytotoxicity, Fc gamma R-mediated phagocytosis and antigen processing and presentation. In addition, the pro-inflammatory, apoptosis and tight junction-related genes were more significantly up-regulated upon infection in the dietary MOS groups to enhance host immune functions and maintain the stability of the intestinal barrier. These results will be helpful to clarify the regulatory mechanism of MOS on the intestinal immunity of M. amblycephala and lay the theoretical foundation for the prevention and protection of fish bacterial diseases.

GaoFen-5 (02) (GF5-02) is a new Chinese operational satellite that was launched on 7 September 2021. The Directional Polarimetric Camera (DPC) is one of the main payloads and is mainly used for the remote sensing monitoring of atmospheric components such as aerosols and water vapor. At present, the DPC is in the stage of on-orbit testing, and no public DPC precipitable water vapor (PWV) data are available. In this study, a PWV retrieval algorithm based on the spectral characteristics of DPC data is developed. The algorithm consists of three parts: (1) the construction of the lookup table, (2) the calculation of water vapor absorption transmittance (WVAT) in the band at 910 nm, and (3) DPC PWV retrieval. The global PWV results derived from DPC data are spatially continuous, which can illustrate the global distribution of water vapor content well. The validation based on the Aerosol Robotic Network (AERONET) PWV data shows that the DPC PWV data have accuracy similar to that of Moderate-resolution Imaging Spectroradiometer (MODIS) PWV data, with coefficient correlation of determination (R2), mean absolute error (MAE), and relative error (RE) of 0.32, 0.30, and 0.93 using the DPC and 0.23, 0.36, and 0.96 using the MODIS, respectively. The results show that our proposed DPC PWV retrieval algorithm is feasible and has high accuracy. By analyzing the errors, we found that the calibration coefficients of the DPC in the 865 nm and 910 nm bands need to be updated.

Change detection technology is an important key to analyze remote sensing data and is of great significance for accurate comprehension of the earth's surface changes. With the continuous development and progress of deep learning technology, fully convolutional neural networks are applied gradually in remote sensing change detection tasks. The present methods mainly encounter the problems of simple network structure, poor detection of small change areas, and poor robustness since they cannot completely obtain the relationships and differences between the features of bi-temporal images. To solve such problems, we propose an attention mechanism-based deep supervision network (ADS-Net) for the change detection of bi-temporal remote sensing images. First, an encoding–decoding full convolutional network is designed with a dual-stream structure. Various level features of bi-temporal images are extracted in the encoding stage, then in the decoding stage, feature maps of different levels are inserted into a deep supervision network with different branches to reconstruct the change map. Ultimately, to obtain the final change detection map, the prediction results of each branch in the deep supervision network are fused with various weights. To highlight the characteristics of change, we propose an adaptive attention mechanism combining spatial and channel features to capture the relationship of different scale changes and achieve more accurate change detection. ADS-Net has been tested on the LEVIR-CD and SVCD datasets of challenging remote sensing image change detection. The results of quantitative analysis and qualitative comparison indicate that the ADS-Net method comprises better effectiveness and robustness compared to the other state-of-the-art change detection methods.

The surface of fresh-cut carrots is apt to white blush, however the physiological and molecular mechanism for this process is not yet fully understood. In this study, exogenous abscisic acid (ABA) and ethylene separately promoted and inhibited the white-blush formation after three days after treatment, respectively. Metabolome analysis found that white-blush components mainly consist of p-hydroxyphenyl lignin and guaiacyl lignin. Transcriptome analysis found an increase in the whiteness values was consistent with the higher expression of genes encoding O-methyltransferase, trans-anol O-methyltransferase, bergaptol O-methyltransferase, caffeic acid 3-O-methyltransferase, phenylalanine ammonia-lyase, and ferulate-5-hydroxylase, together with the lower expression of genes encoding cinnamic acid 4-hydroxylase caffeoyl-CoA O-methyltransferase and 5-O-(4-coumaroyl)-D-quinate 3′-monooxygenase. In conclusion, ABA plays an important role in lignin biosynthesis essential to the formation of white blush in fresh-cut carrots. This is the first report that uncovers the physiological and molecular causes of white blush in fresh-cut carrots, providing a basis for white-blush control in fresh-cut carrots.

CD68 is a highly glycosylated transmembrane glycoprotein that belongs to the lysosome-associated membrane glycoprotein family and is involved in various immune processes. In this study, Megalobrama amblycephala CD68 (MaCD68) was cloned and characterized, and its expression patterns and evolutionary characteristics were analyzed. The coding region of MaCD68 was 987 bp, encoding 328 amino acids, and the predicted protein molecular weight was 34.9 kDa. MaCD68 contained two transmembrane helical structures and 18 predicted N-glycosylation sites. Multiple sequence alignments showed that the MaCD68 protein had high homology with other fish, and their functional sites were also highly conserved. Phylogenetic analysis revealed that MaCD68 and other cypriniformes fish clustered into one branch. Adaptive evolution analysis identified several positively selected sites of teleost CD68 using site and branch-site models, indicating that it was under positive selection pressure during evolution. Quantitative real-time reverse transcription polymerase chain reaction analysis showed that MaCD68 was highly expressed in the head kidney, spleen, and heart. After Aeromonas hydrophila infection, MaCD68 was significantly upregulated in all tested tissues, peaking at 12 h post-infection (hpi) in the kidney and head kidney and at 120 hpi in the liver and spleen, suggesting that MaCD68 participated in the innate immune response of the host against bacterial infection. Immunohistochemical and immunofluorescence analyses also showed that positive signals derived from the MaCD68 protein were further enhanced after bacterial and lipopolysaccharide treatment, which suggested that MaCD68 is involved in the immune response and could be used as a macrophage marker. Biological activity analysis indicated that recombinant MaCD68 (rMaCD68) protein had no agglutination or bactericidal effects on A. hydrophila but did have these effects on Escherichia coli. In conclusion, these results suggest that MaCD68 plays a vital role in the immune response against pathogens, which is helpful in understanding the immune responses and mechanisms of M. amblycephala.

Alcohol can cause injury and lead to an inflammatory response in the liver. The NF-κB/AMPK signaling pathway plays a vital role in regulating intracellular inflammatory cytokine levels. In this study, corn oligopeptides (CPs), as the research objects, were obtained from corn gluten meal, and their regulation of the activation of the Kupffer cell NF-κB/AMPK signal pathway induced by LPS was investigated. Results showed that ALT, AST, and inflammatory cytokines in mice serum after the administration of CPs at 0.2, 0.4, and 0.8 g/kg of body weight displayed a distinct (p < 0.05) reduction. On the other hand, the CPs also inhibited the expression of recognized receptor CD14 and TLR4, down-regulated P-JNK, P-ERK, and P-p-38, and thus inhibited inflammatory cytokine levels in Kupffer cells (KCs). Furthermore, four kinds of dipeptides with a leucine residue at the C-terminus that might exhibit down-regulated inflammatory cytokines in the NF-κB/AMPK signaling pathway functions were detected using HPLC-MS/MS. These results indicated that CPs have a potential application value in acute alcoholic liver disease.

Currently, the non-maximum suppression (NMS) algorithm is a commonly used method in the post-processing stage of object detection. However, the NMS algorithm cannot effectively eliminate missing and false object detection results because of the simple constraint condition. To solve the problem of the poor detection effect in highly overlapping dense object scenes in the traditional NMS algorithm, we design an RGB-D object detection network model based on the YOLO v3 framework, and using level-by-level metaphase fusion on the RGB and depth information, we propose an improved NMS algorithm which fuses depth characteristics. According to the depth of the object in the detection boxes, it is determined whether another object is the same object in highly overlapping detection boxes, and the average depth of the internal pixels in the detection boxes is calculated as a penalty term, then the penalty term is added to the detection box score to obtain a new constraint condition for non-maximum suppression. The experimental results on the NYU Depth V2 dataset show that the mean average precision (mAP) of the Depth Fusion NMS algorithm proposed in this paper is 0.8%, 0.5% and 0.3% higher than those of the Greedy-NMS, Soft NMS-L and Soft NMS-G methods, respectively. After comparison and analysis, our method can not only detect more overlapping objects but also achieve a better object localization accuracy.

Microglia are the primary resident immune cells of the central nervous system that maintain physiological homeostasis in the brain and contribute to the pathogenesis of many psychiatric disorders and neurodegenerative diseases. Due to the lack of appropriate human cellular models, it is difficult to study the basic pathophysiological processes linking microglia to brain diseases. In this study, we adopted a microglia-like cellular model derived from peripheral blood monocytes with granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-34 (IL-34). We characterized and validated this in vitro cellular model by morphology, immunocytochemistry, gene expression profiles, and functional study. Our results indicated that the iMG cells developed typical microglial ramified morphology, expressed microglial specific surface markers (P2RY12 and TMEM119), and possessed phagocytic activity. Principal component analyses and multidimensional scaling analyses of RNA-seq data showed that iMG cells were distinct from monocytes and induced macrophages (iMacs) but clustered closer to human microglia and hiPSC-induced microglia. Heatmap analyses also found that iMG cells, but not monocytes, were closely clustered with human primary microglia. Further pathway and relative expression analysis indicated that unique genes from iMG cells were involved in the regulation of the complement system, especially in the synapse and ion transport. Overall, our data demonstrated that the iMG model mimicked many features of the brain resident microglia, highlighting its utility in the study of microglial function in many brain diseases, such as schizophrenia and Alzheimer's disease (AD).

Polychlorinated biphenyls (PCBs) are well-known persistent organic pollutants; they have toxic effects on the immune system, reproductive system, and endocrine system by changing the metabolism of the body. To elucidate the underlying molecular mechanism, the clam Meretrix meretrix was exposed to 10 and 1000 ng/L Aroclor 1254 and natural seawater (control). Samples from clams exposed to natural seawater and those exposed to Aroclor 1254 for 1 and 3 days were individually collected for transcriptome analysis. After assembly, more than 535,157 transcripts with a mean length of 949 bp and an N50 length of 1279 bp were obtained; a final set of 177,142 unigenes was generated. In the present study, 5101 differentially expressed genes were identified. The differentially expressed genes were related to detoxification metabolism, oxidative stress, immune response, and endocrine system disruption. Of these genes, under the Aroclor 1254 exposure, cytochrome P450 20A1 (2.06–4.46 folds), glutathione S-transferase (2.25–3.80 folds), multidrug resistance-associated protein 1-like (1.49–2.92 folds), peroxidase-like protein (1.33–4.26 folds), lysozyme (1.61–2.05 folds), bcl-2 like 1 protein (1.14–2.29 folds) and vitellogenin (1.09–1.19 folds) showed been significantly induced expressed. At the same time, some genes were down regulated, including cytochrome P450 2J5 (−1.20 ~ −2.86 folds), cytochrome P450 3A24 (−1.40 ~ −4.08 folds), C1q (−1.27 ~ −1.66 folds), Sulfotransferase (−1.51 ~ −1.84 folds), monocarboxylate transporter 10 (−1.30 ~ −4.70 folds), 3-beta hydroxysteroid dehydrogenase (−1.43 ~ −2.81 folds) and beta-galactosidase (−1.23 ~ −2.23 folds). Furthermore, it showed that the expression levels of CYP2J5, glutathione S-transferase, 3-beta hydroxysteroid dehydrogenase and beta-galactosidase had time responses and dose responses. The present study provided insights into the toxic effects of Aroclor 1254 exposure in M. meretrix.

With the progress of society and the rapid development of computer technology, rumors arise on social media, which seriously affects the social economy. How to detect rumors accurately and rapidly has become one hot research topic. In this paper, a new early rumor detection model is proposed. The aim of this model is to increase the efficiency and the accuracy of rumor detection simultaneously. Specifically, in this model, the input data is firstly refined through account filtering and data standardization, then the BiGRU is used to consider the context relationship, and a reinforcement learning algorithm is applied to detection. Experimental results show that compared with other early rumor detection models (e.g., checkpoints), the accuracy of the proposed model is improved by 0.5% with the same speed, which testifies the effectiveness of this model.

Schizophrenia is a complex disorder with many comorbid conditions. In this study, we used polygenic risk scores (PRSs) from schizophrenia and comorbid traits to explore consistent cluster structure in schizophrenia patients. With 10 comorbid traits, we found a stable 4-cluster structure in two datasets (MGS and SSCCS). When the same traits and parameters were applied for the patients in a clinical trial of antipsychotics, the CATIE study, a 5-cluster structure was observed. One of the 4 clusters found in the MGS and SSCCS was further split into two clusters in CATIE, while the other 3 clusters remained unchanged. For the 5 CATIE clusters, we evaluated their association with the changes of clinical symptoms, neurocognitive functions, and laboratory tests between the enrollment baseline and the end of Phase I trial. Class I was found responsive to treatment, with significant reduction for the total, positive, and negative symptoms (p=0.0001, 0.0099, and 0.0028, respectively), and improvement for cognitive functions (VIGILANCE, p=0.0099; PROCESSING SPEED, p=0.0006; WORKING MEMORY, p=0.0023; and REASONING, p=0.0015). Class II had modest reduction of positive symptoms (p=0.0492) and better PROCESSING SPEED (p=0.0071). Class IV had a specific reduction of negative symptoms (p=0.0111) and modest cognitive improvement for all tested domains. Interestingly, Class IV was also associated with decreased lymphocyte counts and increased neutrophil counts, an indication of ongoing inflammation or immune dysfunction. In contrast, Classes III and V showed no symptom reduction but a higher level of phosphorus. Overall, our results suggest that PRSs from schizophrenia and comorbid traits can be utilized to classify patients into subtypes with distinctive clinical features. This genetic susceptibility based subtyping may be useful to facilitate more effective treatment and outcome prediction.

Rice noodles is a common food, but it is faced with the characteristics of hard texture and poor nutrition after aging. Quinoa is rich in dietary fiber and nutritious and can enrich the color and taste of rice noodles. In this paper, red quinoa is used as an additive, gelatinization time, quinoa added amount, and water added are selected as influencing factors on a single factor basis, and the hardness of rice quinoa gel is used as the response value to carry out experiments to optimize rice quinoa gelling Glue production process. The results show that the best process is: gelatinization time 30min, quinoa addition amount 30%, material to water ratio 1:2 (g/mL). The test product of this formula has uniform color, uniform gel, strong aroma, good taste and fine mouthfeel.

A novel all-fiber low-pedestal spectral compression scheme is proposed and demonstrated. The scheme is based on an anomalously dispersive single-mode fiber (SMF) cascading a nonlinear optical loop mirror with a highly nonlinear fiber (HNLF) in the loop. Both numerical and experimental results show that the spectral pedestal after spectral compression in the HNLF can be efficiently suppressed by the nonlinear optical loop mirror through the chirp-related intensity filtering effect. The measured spectral pedestal energy ratio is 9.59% using the proposed scheme, which is nearly a quarter of that using the conventional alternative based on an anomalously dispersive SMF followed by a feedthrough HNLF.

Large-scale three-dimensional (3D) reconstruction from multi-view images is used to generate 3D mesh surfaces, which are usually built for urban areas and are widely applied in many research hotspots, such as smart cities. Their simplification is a significant step for 3D roaming, pattern recognition, and other research fields. The simplification quality has been assessed in several studies. On the one hand, almost all studies on surface simplification have measured simplification errors using the surface comparison tool Metro, which does not preserve sufficient detail. On the other hand, the reconstruction precision of urban surfaces varies as a result of homogeneity or heterogeneity. Therefore, it is difficult to assess simplification quality without surface classification. These difficulties are addressed in this study by first classifying urban surfaces into planar surfaces, detailed surfaces, and urban frameworks according to the simplification errors of different types of surfaces and then measuring these errors after sampling. A series of assessment indexes are also provided to contribute to the advancement of simplification algorithms.

There are two independent serotonin (5-HT) systems of organization: one in the central nervous system and the other in the periphery. 5-HT affects feeding behavior and obesity in the central nervous system. On the other hand, peripheral 5-HT also may play an important role in obesity, as it has been reported that 5-HT regulates glucose and lipid metabolism. Here we show that the intraperitoneal injection of 5-HT to mice inhibits weight gain, hyperglycemia and insulin resistance and completely prevented the enlargement of intra-abdominal adipocytes without having any effect on food intake when on a high fat diet, but not on a chow diet. 5-HT increased energy expenditure, O2 consumption and CO2 production. This novel metabolic effect of peripheral 5-HT is critically related to a shift in the profile of muscle fiber type from fast/glycolytic to slow/oxidative in soleus muscle. Additionally, 5-HT dramatically induced an increase in the mRNA expression of peroxisome proliferator-activated receptor coactivator 1α (PGC-1α)-b and PGC-1α-c in soleus muscle. The elevation of these gene mRNA expressions by 5-HT injection was inhibited by treatment with 5-HT receptor (5HTR) 2A or 7 antagonists. Our results demonstrate that peripheral 5-HT may play an important role in the relief of obesity and other metabolic disorders by accelerating energy consumption in skeletal muscle.

In mice, peripheral 5-HT induces an increase in the plasma concentrations of glucose, insulin and bile acids, and a decrease in plasma triglyceride, NEFA and cholesterol concentrations. However, given the unique characteristics of the metabolism of ruminants relative to monogastric animals, the physiological role of peripheral 5-HT on glucose and lipid metabolism in sheep remains to be established. Therefore, in this study, we investigated the effect of 5-HT on the circulating concentrations of metabolites and insulin using five 5-HT receptor (5HTR) antagonists in sheep. After fasting for 24 h, sheep were intravenously injected with 5-HT, following which-, plasma glucose, insulin, triglyceride and NEFA concentrations were significantly elevated. In contrast, 5-HT did not affect the plasma cholesterol concentration, and it induced a decrease in bile acid concentrations. Increases in plasma glucose and insulin concentrations induced by 5-HT were attenuated by pre-treatment with Methysergide, a 5HTR 1, 2 and 7 antagonist. Additionally, decreased plasma bile acid concentrations induced by 5-HT were blocked by pre-treatment with Ketanserin, a 5HTR 2A antagonist. However, none of the 5HTR antagonists inhibited the increase in plasma triglyceride and NEFA levels induced by 5-HT. On the other hand, mRNA expressions of 5HTR1D and 1E were observed in the liver, pancreas and skeletal muscle. These results suggest that there are a number of differences in the physiological functions of peripheral 5-HT with respect to lipid metabolism between mice and sheep, though its effect on glucose metabolism appears to be similar between these species.

Integrating evidence from multiple domains is useful in prioritizing disease candidate genes for subsequent testing. We ranked all known human genes (n=3819) under linkage peaks in the Irish Study of High-Density Schizophrenia Families using three different evidence domains: 1) a meta-analysis of microarray gene expression results using the Stanley Brain collection, 2) a schizophrenia protein-protein interaction network, and 3) a systematic literature search. Each gene was assigned a domain-specific p-value and ranked after evaluating the evidence within each domain. For comparison to this ranking process, a large-scale candidate gene hypothesis was also tested by including genes with Gene Ontology terms related to neurodevelopment. Subsequently, genotypes of 3725 SNPs in 167 genes from a custom Illumina iSelect array were used to evaluate the top ranked vs. hypothesis selected genes. Seventy-three genes were both highly ranked and involved in neurodevelopment (category 1) while 42 and 52 genes were exclusive to neurodevelopment (category 2) or highly ranked (category 3), respectively. The most significant associations were observed in genes PRKG1, PRKCE, and CNTN4 but no individual SNPs were significant after correction for multiple testing. Comparison of the approaches showed an excess of significant tests using the hypothesis-driven neurodevelopment category. Random selection of similar sized genes from two independent genome-wide association studies (GWAS) of schizophrenia showed the excess was unlikely by chance. In a further meta-analysis of three GWAS datasets, four candidate SNPs reached nominal significance. Although gene ranking using integrated sources of prior information did not enrich for significant results in the current experiment, gene selection using an a priori hypothesis (neurodevelopment) was superior to random selection. As such, further development of gene ranking strategies using more carefully selected sources of information is warranted.

The influx of Ca(2+) through calcium-permeable nicotinic acetylcholine receptors (nAChRs) leads to activation of various downstream processes that may be relevant to nicotine-mediated behaviors. The calcium activated protein, calcium/calmodulin-dependent protein kinase IV (CaMKIV) phosphorylates the downstream transcription factor cyclic AMP response element binding protein (CREB), which mediates nicotine responses; however the role of CaMKIV in nicotine dependence is unknown. Given the proposed role of CaMKIV in CREB activation, we hypothesized that CaMKIV might be a crucial molecular component in the development of nicotine dependence. Using male CaMKIV genetically modified mice, we found that nicotine reward is attenuated in CaMKIV knockout (-/-) mice, but cocaine reward is enhanced in these mice. CaMKIV protein levels were also increased in the nucleus accumbens of C57Bl/6 mice after nicotine reward. In a nicotine withdrawal assessment, anxiety-related behavior, but not somatic signs or the hyperalgesia response are attenuated in CaMKIV -/- mice. To complement our animal studies, we also conducted a human genetic association analysis and found that variants in the CaMKIV gene are associated with a protective effect against nicotine dependence. Taken together, our results support an important role for CaMKIV in nicotine reward, and suggest that CaMKIV has opposing roles in nicotine and cocaine reward. Further, CaMKIV mediates affective, but not physical nicotine withdrawal signs, and has a protective effect against nicotine dependence in human genetic association studies. These findings further indicate the importance of calcium-dependent mechanisms in mediating behaviors associated with drugs of abuse.

Individuals with schizophrenia tend to be heavy smokers and are at high risk for tobacco dependence. However, the nature of the comorbidity is not entirely clear. We previously reported evidence for association of schizophrenia with SNPs and SNP haplotypes in a region of chromosome 5q containing the SPEC2, PDZ-GEF2 and ACSL6 genes. In this current study, analysis of the control subjects of the Molecular Genetics of Schizophrenia (MGS) sample showed similar pattern of association with number of cigarettes smoked per day (numCIG) for the same region. To further test if this locus is associated with tobacco smoking as measured by numCIG and FTND, we conducted replication and meta-analysis in 12 independent samples (n>16,000) for two markers in ACSL6 reported in our previous schizophrenia study. In the meta-analysis of the replication samples, we found that rs667437 and rs477084 were significantly associated with numCIG (p = 0.00038 and 0.00136 respectively) but not with FTND scores. We then used in vitro and in vivo techniques to test if nicotine exposure influences the expression of ACSL6 in brain. Primary cortical culture studies showed that chronic (5-day) exposure to nicotine stimulated ACSL6 mRNA expression. Fourteen days of nicotine administration via osmotic mini pump also increased ACSL6 protein levels in the prefrontal cortex and hippocampus of mice. These increases were suppressed by injection of the nicotinic receptor antagonist mecamylamine, suggesting that elevated expression of ACSL6 requires nicotinic receptor activation. These findings suggest that variations in the ACSL6 gene may contribute to the quantity of cigarettes smoked. The independent associations of this locus with schizophrenia and with numCIG in non-schizophrenic subjects suggest that this locus may be a common liability to both conditions.

Recently, genetic association findings for nicotine dependence, smoking behavior, and smoking-related diseases converged to implicate the chromosome 15q25.1 region, which includes the CHRNA5-CHRNA3-CHRNB4 cholinergic nicotinic receptor subunit genes. In particular, association with the nonsynonymous CHRNA5 SNP rs16969968 and correlates has been replicated in several independent studies. Extensive genotyping of this region has suggested additional statistically distinct signals for nicotine dependence, tagged by rs578776 and rs588765. One goal of the Consortium for the Genetic Analysis of Smoking Phenotypes (CGASP) is to elucidate the associations among these markers and dichotomous smoking quantity (heavy versus light smoking), lung cancer, and chronic obstructive pulmonary disease (COPD). We performed a meta-analysis across 34 datasets of European-ancestry subjects, including 38,617 smokers who were assessed for cigarettes-per-day, 7,700 lung cancer cases and 5,914 lung-cancer-free controls (all smokers), and 2,614 COPD cases and 3,568 COPD-free controls (all smokers). We demonstrate statistically independent associations of rs16969968 and rs588765 with smoking (mutually adjusted p-values

Schizophrenia (SZ) is a heritable, complex mental disorder. We have seen limited success in finding causal genes for schizophrenia from numerous conventional studies. Protein interaction network and pathway-based analysis may provide us an alternative and effective approach to investigating the molecular mechanisms of schizophrenia.We selected a list of schizophrenia candidate genes (SZGenes) using a multi-dimensional evidence-based approach. The global network properties of proteins encoded by these SZGenes were explored in the context of the human protein interactome while local network properties were investigated by comparing SZ-specific and cancer-specific networks that were extracted from the human interactome. Relative to cancer genes, we observed that SZGenes tend to have an intermediate degree and an intermediate efficiency on a perturbation spreading throughout the human interactome. This suggested that schizophrenia might have different pathological mechanisms from cancer even though both are complex diseases. We conducted pathway analysis using Ingenuity System and constructed the first schizophrenia molecular network (SMN) based on protein interaction networks, pathways and literature survey. We identified 24 pathways overrepresented in SZGenes and examined their interactions and crosstalk. We observed that these pathways were related to neurodevelopment, immune system, and retinoic X receptor (RXR). Our examination of SMN revealed that schizophrenia is a dynamic process caused by dysregulation of the multiple pathways. Finally, we applied the network/pathway approach to identify novel candidate genes, some of which could be verified by experiments.This study provides the first comprehensive review of the network and pathway characteristics of schizophrenia candidate genes. Our preliminary results suggest that this systems biology approach might prove promising for selection of candidate genes for complex diseases. Our findings have important implications for the molecular mechanisms for schizophrenia and, potentially, other psychiatric disorders.

Apoptosis has been speculated to be involved in schizophrenia. In a previously study, we reported the association of the MEGF10 gene with the disease. In this study, we followed the apoptotic engulfment pathway involving the MEGF10, GULP1, ABCA1 and ABCA7 genes and tested their association with the disease.Ten, eleven and five SNPs were genotyped in the GULP1, ABCA1 and ABCA7 genes respectively for the ISHDSF and ICCSS samples. In all 3 genes, we observed nominally significant associations. Rs2004888 at GULP1 was significant in both ISHDSF and ICCSS samples (p = 0.0083 and 0.0437 respectively). We sought replication in independent samples for this marker and found highly significant association (p = 0.0003) in 3 Caucasian replication samples. But it was not significant in the 2 Chinese replication samples. In addition, we found a significant 2-marker (rs2242436 * rs3858075) interaction between the ABCA1 and ABCA7 genes in the ISHDSF sample (p = 0.0022) and a 3-marker interaction (rs246896 * rs4522565 * rs3858075) amongst the MEGF10, GULP1 and ABCA1 genes in the ICCSS sample (p = 0.0120). Rs3858075 in the ABCA1 gene was involved in both 2- and 3-marker interactions in the two samples.From these data, we concluded that the GULP1 gene and the apoptotic engulfment pathway are involved in schizophrenia in subjects of European ancestry and multiple genes in the pathway may interactively increase the risks to the disease.