Chicken or Porcine Aminopeptidase N Mediates Cellular Entry of Pseudoviruses Carrying Spike Glycoprotein from the Avian Deltacoronaviruses HKU11, HKU13, and HKU17.

Members of deltacoronavirus (DCoV) have mostly been identified in diverse avian species as natural reservoirs, though the porcine DCoV (PDCoV) is a major swine enteropathogenic virus with global spread. The important role of aminopeptidase N (APN) orthologues from various mammalian and avian species in PDCoV cellular entry and interspecies transmission has been revealed recently. In this study, comparative analysis indicated that three avian DCoVs, bulbul DCoV HKU11, munia DCoV HKU13, and sparrow DCoV HKU17 (Chinese strain), and PDCoV in the subgenera Buldecovirus are grouped together at whole-genome levels; however, the spike (S) glycoprotein and its S1 subunit of HKU17 are more closely related to night heron DCoV HKU19 in Herdecovirus. Nevertheless, the S1 protein of HKU11, HKU13, or HKU17 bound to or interacted with chicken APN (chAPN) or porcine APN (pAPN) by flow cytometry analysis of cell surface expression of APN and by coimmunoprecipitation in APN-overexpressing cells. Expression of chAPN or pAPN allowed entry of pseudotyped lentiviruses with the S proteins from HKU11, HKU13 and HKU17 into nonsusceptible cells and natural avian and porcine cells, which could be inhibited by the antibody against APN or anti-PDCoV-S1. APN knockdown by siRNA or knockout by CRISPR/Cas9 in chicken or swine cell lines significantly or almost completely blocked infection of these pseudoviruses. Hence, we demonstrate that HKU11, HKU13, and HKU17 with divergent S genes likely engage chAPN or pAPN to enter the cells, suggesting a potential interspecies transmission from wild birds to poultry and from birds to mammals by certain avian DCoVs. IMPORTANCE The receptor usage of avian deltacoronaviruses (DCoVs) has not been investigated thus far, though porcine deltacoronavirus (PDCoV) has been shown to utilize aminopeptidase N (APN) as a cell receptor. We report here that chicken or porcine APN also mediates cellular entry by three avian DCoV (HKU11, HKU13, and HKU17) spike pseudoviruses, and the S1 subunit of three avian DCoVs binds to APN in vitro and in the surface of avian and porcine cells. The results fill the gaps in knowledge about the avian DCoV receptor and elucidate important insights for the monitoring and prevention of potential interspecies transmission of certain avian DCoVs. In view of the diversity of DCoVs, whether this coronavirus genus will cause novel virus to emerge in other mammals from birds, are worthy of further surveillance and investigation.

Bile acids promote the caveolae-associated entry of swine acute diarrhea syndrome coronavirus in porcine intestinal enteroids.

Intestinal microbial metabolites have been increasingly recognized as important regulators of enteric viral infection. However, very little information is available about which specific microbiota-derived metabolites are crucial for swine enteric coronavirus (SECoV) infection in vivo. Using swine acute diarrhea syndrome (SADS)-CoV as a model, we were able to identify a greatly altered bile acid (BA) profile in the small intestine of infected piglets by untargeted metabolomic analysis. Using a newly established ex vivo model-the stem cell-derived porcine intestinal enteroid (PIE) culture-we demonstrated that certain BAs, cholic acid (CA) in particular, enhance SADS-CoV replication by acting on PIEs at the early phase of infection. We ruled out the possibility that CA exerts an augmenting effect on viral replication through classic farnesoid X receptor or Takeda G protein-coupled receptor 5 signaling, innate immune suppression or viral attachment. BA induced multiple cellular responses including rapid changes in caveolae-mediated endocytosis, endosomal acidification and dynamics of the endosomal/lysosomal system that are critical for SADS-CoV replication. Thus, our findings shed light on how SECoVs exploit microbiome-derived metabolite BAs to swiftly establish viral infection and accelerate replication within the intestinal microenvironment.

Evaluation of immunogenicity and protective efficacy of the outer membrane porin F (OprF) against Pseudomonas plecoglossicida in large yellow croaker (Larimichthys crocea).

Large yellow croaker (Larimichthys crocea) farming dominates the marine aquaculture industry in China. However, the epidemic outbreaks of visceral white nodules disease (VWND), caused by bacterial pathogen Pseudomonas plecoglossicida, have emerged as a significant concern within the large yellow croaker industry. Although vaccination is considered to be an effective method for preventing and controlling P. plecoglossicida infection, there is currently no commercially available vaccine targeting this bacterium. In the present study, the outer membrane porin F (OprF) of P. plecoglossicida was characterized and revealed a high sequence similarity with that of other Pseudomonas species. The recombinant OprF protein (rOprF) produced in Escherichia coli was then evaluated for its immunogenicity and protective role against P. plecoglossicida in large yellow croaker. The rOprF was identified to have immunogenicity by Western blot using large yellow croaker anti-P. plecoglossicida sera. Additionally, the indirect immunofluorescence assay (IIFA) provided evidence indicating the surface exposure of OprF in P. plecoglossicida. Fish vaccinated twice via intraperitoneal (IP) injection with the purified rOprF combined with commercial adjuvant ISA 763A VG exhibited a relative percent survival (RPS) of 70.60% after challenge with virulent P. plecoglossicida strain through immersion. The administration of rOprF resulted in a notable increase in specific serum antibody levels and serum lysozyme activity compared to the control groups. The immune-related genes in the spleen and head kidney of rOprF-vaccinated fish were remarkably upregulated compared with the PBS-vaccinated sham group after the P. plecoglossicida challenge. In summary, the findings of this study suggest that rOprF exhibits considerable potential in inducing a robust immune response, making it a viable candidate for vaccination against P. plecoglossicida infection in large yellow croaker.

Complete genome sequence and characterization of four Decapod iridescent virus 1 isolates from crab and shrimp.

Decapod iridescent virus 1 (DIV1) is an emerging viral pathogen that infects diverse freshwater and marine crustacean species and causes considerable economic losses that seriously threaten crustacean farming and has caused enormous financial losses in recent years. In this study, we detected DIV1 from diseased crabs, with clinical symptoms such as loss of vitality and white gill filaments with edema, in a Marsupenaeus japonicus and Portunus trituberculatus polyculture pond. Four DIV1 isolates from crab samples (two isolates) and shrimp samples (two isolates) were sequenced and assembled successfully. Molecular characterization and phylogenetic analysis of the four DIV1 isolates were conducted. The DIV1 isolates from crab samples have a close genetic relationship with shrimp DIV1s, indicating the viruses share the same ancestor with those from shrimps. Our study provides valuable insights into disease prevention and control of the shrimp-crab polyculture system.

Roles of Two Major Domains of the Porcine Deltacoronavirus S1 Subunit in Receptor Binding and Neutralization.

Determination of the mechanisms of interspecies transmission is of great significance for the prevention of epidemic diseases caused by emerging coronaviruses (CoVs). Recently, porcine deltacoronavirus (PDCoV) was shown to exhibit broad host cell range mediated by surface expression of aminopeptidase N (APN), and humans have been reported to be at risk of PDCoV infection. In the present study, we first demonstrated overexpression of APN orthologues from various species, including mice and felines, in the APN-deficient swine small intestine epithelial cells permitted PDCoV infection, confirming that APN broadly facilitates PDCoV cellular entry and perhaps subsequent interspecies transmission. PDCoV was able to limitedly infect mice in vivo, distributing mainly in enteric and lymphoid tissues, suggesting that mice may serve as a susceptible reservoir of PDCoV. Furthermore, elements (two glycosylation sites and four aromatic amino acids) on the surface of domain B (S1B) of the PDCoV spike glycoprotein S1 subunit were identified to be critical for cellular surface binding of APN orthologues. However, both domain A (S1A) and domain B (S1B) were able to elicit potent neutralizing antibodies against PDCoV infection. The antibodies against S1A inhibited the hemagglutination activity of PDCoV using erythrocytes from various species, which might account for the neutralizing capacity of S1A antibodies partially through a blockage of sialic acid binding. The study reveals the tremendous potential of PDCoV for interspecies transmission and the role of two major PDCoV S1 domains in receptor binding and neutralization, providing a theoretical basis for development of intervention strategies. IMPORTANCE Coronaviruses exhibit a tendency for recombination and mutation, which enables them to quickly adapt to various novel hosts. Previously, orthologues of aminopeptidase N (APN) from mammalian and avian species were found to be associated with porcine deltacoronavirus (PDCoV) cellular entry in vitro. Here, we provide in vivo evidence that mice are susceptible to PDCoV limited infection. We also show that two major domains (S1A and S1B) of the PDCoV spike glycoprotein involved in APN receptor binding can elicit neutralizing antibodies, identifying two glycosylation sites and four aromatic amino acids on the surface of the S1B domain critical for APN binding and demonstrating that the neutralization activity of S1A antibodies is partially attributed to blockage of sugar binding activity. Our findings further implicate PDCoV's great potential for interspecies transmission, and the data of receptor binding and neutralization may provide a basis for development of future intervention strategies.

Discovery of a novel short peptide with efficacy in accelerating the healing of skin wounds.

Despite extensive efforts to develop efficacious therapeutic approaches, the treatment of skin wounds remains a considerable clinical challenge. Existing remedies cannot sufficiently meet current needs, so the discovery of novel pro-healing agents is of growing importance. In the current research, we identified a novel short peptide (named RL-QN15, primary sequence 'QNSYADLWCQFHYMC') from Rana limnocharis skin secretions, which accelerated wound healing in mice. Exploration of the underlying mechanisms showed that RL-QN15 activated the MAPK and Smad signaling pathways, and selectively modulated the secretion of cytokines from macrophages. This resulted in the proliferation and migration of skin cells and dynamic regulation of TGF-ß1 and TGF-ß3 in wounds, which accelerated re-epithelialization and granulation tissue formation and thus skin regeneration. Moreover, RL-QN15 showed significant therapeutic potency against chronic wounds, skin fibrosis, and oral ulcers. Our results highlight frog skin secretions as a potential treasure trove of bioactive peptides with healing activity. The novel peptide (RL-QN15) identified in this research shows considerable capacity as a candidate for the development of novel pro-healing agents.

Mesoporous polydopamine nanoparticles carrying peptide RL-QN15 show potential for skin wound therapy.

BACKGROUND: Skin wound healing remains a considerable clinical challenge, thus stressing the urgent need for the development of new interventions to promote repair. Recent researches indicate that both peptides and nanoparticles may be potential therapies for the treatment of skin wounds. METHODS: In the current study, the mesoporous polydopamine (MPDA) nanoparticles were prepared and the peptide RL-QN15 that was previously identified from amphibian skin secretions and exhibited significant potential as a novel prohealing agent was successfully loaded onto the MPDA nanoparticles, which was confirmed by results of analysis of scanning electron microscopy and fourier transform infrared spectroscopy. The encapsulation efficiency and sustained release rate of RL-QN15 from the nanocomposites were determined. The prohealing potency of nanocomposites were evaluated by full-thickness injured wounds in both mice and swine and burn wounds in mice. RESULTS: Our results indicated that, compared with RL-QN15 alone, the prohealing potency of nanocomposites of MPDA and RL-QN15 in the full-thickness injured wounds and burn wounds in mice was increased by up to 50 times through the slow release of RL-QN15. Moreover, the load on the MPDA obviously increased the prohealing activities of RL-QN15 in full-thickness injured wounds in swine. In addition, the obvious increase in the prohealing potency of nanocomposites of MPDA and RL-QN15 was also proved by the results from histological analysis. CONCLUSIONS: Based on our knowledge, this is the first research to report that the load of MPDA nanoparticles could significantly increase the prohealing potency of peptide and hence highlighted the promising potential of MPDA nanoparticles-carrying peptide RL-QN15 for skin wound therapy.

Broad Cross-Species Infection of Cultured Cells by Bat HKU2-Related Swine Acute Diarrhea Syndrome Coronavirus and Identification of Its Replication in Murine Dendritic Cells In Vivo Highlight Its Potential for Diverse Interspecies Transmission.

Outbreaks of severe diarrhea in neonatal piglets in Guangdong, China, in 2017 resulted in the isolation and discovery of a novel swine enteric alphacoronavirus (SeACoV) derived from the species Rhinolophus bat coronavirus HKU2 (Y. Pan, X. Tian, P. Qin, B. Wang, et al., Vet Microbiol 211:15-21, 2017). SeACoV was later referred to as swine acute diarrhea syndrome CoV (SADS-CoV) by another group (P. Zhou, H. Fan, T. Lan, X.-L. Yang, et al., Nature 556:255-258, 2018). The present study was set up to investigate the potential species barriers of SADS-CoV in vitro and in vivo We first demonstrated that SADS-CoV possesses a broad species tropism and is able to infect cell lines from diverse species, including bats, mice, rats, gerbils, hamsters, pigs, chickens, nonhuman primates, and humans. Trypsin contributes to but is not essential for SADS-CoV propagation in vitro Furthermore, C57BL/6J mice were inoculated with the virus via oral or intraperitoneal routes. Although the mice exhibited only subclinical infection, they supported viral replication and prolonged infection in the spleen. SADS-CoV nonstructural proteins and double-stranded RNA were detected in splenocytes of the marginal zone on the edge of lymphatic follicles, indicating active replication of SADS-CoV in the mouse model. We identified that splenic dendritic cells (DCs) are the major targets of virus infection by immunofluorescence and flow cytometry approaches. Finally, we demonstrated that SADS-CoV does not utilize known CoV receptors for cellular entry. The ability of SADS-CoV to replicate in various cells lines from a broad range of species and the unexpected tropism for murine DCs provide important insights into the biology of this bat-origin CoV, highlighting its possible ability to cross interspecies barriers.IMPORTANCE Infections with bat-origin coronaviruses (CoVs) (severe acute respiratory syndrome CoV [SARS-CoV] and Middle East respiratory syndrome CoV [MERS-CoV]) have caused severe illness in humans after "host jump" events. Recently, a novel bat-HKU2-like CoV named swine acute diarrhea syndrome CoV (SADS-CoV) has emerged in southern China, causing lethal diarrhea in newborn piglets. It is important to assess the species barriers of SADS-CoV infection since the animal hosts (other than pigs and bats) and zoonotic potential are still unknown. An in vitro susceptibility study revealed a broad species tropism of SADS-CoV, including various rodent and human cell lines. We established a mouse model of SADS-CoV infection, identifying its active replication in splenic dendritic cells, which suggests that SADS-CoV has the potential to infect rodents. These findings highlight the potential cross-species transmissibility of SADS-CoV, although further surveillance in other animal populations is needed to fully understand the ecology of this bat-HKU2-origin CoV.

Porcine Deltacoronavirus Engages the Transmissible Gastroenteritis Virus Functional Receptor Porcine Aminopeptidase N for Infectious Cellular Entry.

Identification of cellular receptors used by coronavirus (CoV) entry into the host cells is critical to an understanding of pathogenesis and to development of intervention strategies. The fourth CoV genus, Deltacoronavirus, evolutionarily related to the Gammacoronavirus, has just been defined recently. In the current study, we demonstrate that porcine aminopeptidase N (pAPN) acts as a cross-genus CoV functional receptor for both enteropathogenic porcine deltacoronovirus (PDCoV) and alphacoronovirus (AlphaCoV) (transmissible gastroenteritis virus [TGEV]) based upon three lines of evidence. First, the soluble S1 protein of PDCoV bound to the surface of target porcine cell lines known to express pAPN as efficiently as TGEV-S1, which could be blocked by soluble pAPN pretreatment. Second, both PDCoV-S1 and TGEV-S1 physically recognized and interacted with pAPN by coimmunoprecipitation in pAPN cDNA-transfected cells and by dot blot hybridization assay. Finally, exogenous expression of pAPN in refractory cells conferred susceptibility to PDCoV-S1 binding and to PDCoV entry and productive infection. PDCoV-S1 appeared to have a lower pAPN-binding affinity and likely consequent lower infection efficiency in pAPN-expressing refractory cells than TGEV-S1, suggesting that there may be differences between these two viruses in the virus-binding regions in pAPN. This study paves the way for dissecting the molecular mechanisms of PDCoV-host interactions and pathogenesis as well as facilitates future vaccine development and intervention strategies against PDCoV infection.IMPORTANCE The emergence of new human and animal coronaviruses is believed to have occurred through interspecies transmission that is mainly mediated by a species-specific receptor of the host. Among the four genera of the Coronavirinae, a couple of functional receptors for the representative members in the genera Alphacoronavirus and Betacoronavirus have been identified, whereas receptors for Gammacoronavirus and Deltacoronavirus, which are believed to originate from birds, are still unknown. Porcine coronaviruses, including the newly discovered porcine deltacoronavirus (PDCoV) associated with diarrhea in newborn piglets, have posed a serious threat to the pork industry in Asia and North America. Here, we report that PDCoV employs the alphacoronavirus TGEV functional receptor porcine aminopeptidase N (pAPN) for cellular entry, demonstrating the usage of pAPN as a cross-genus CoV functional receptor. The identification of the PDCoV receptor provides another example of the expanded host range of CoV and paves the way for further investigation of PDCoV-host interaction and pathogenesis.

Targeted silencing of MYCL1 by RNA interference inhibits migration and invasion of MGC-803 gastric cancer cells.

MYCL1 protein expression encoded by a proto-oncogene MYCL1, a member of the MYC family, is correlated with poor prognosis in gastric cancer patients. Nevertheless, the role of MYCL1 in gastric cancer cells remains unknown. In this study, the expression levels of MYCL1 mRNA and protein were downregulated by lentiviral-mediated RNA interference (RNAi) in the MGC-803 gastric cancer cell line. Then, the influence of MYCL1 on the biological behaviour of gastric cancer cells was investigated. Finally, a stable animal model of the MGC-803 human gastric cancer tumour model in nude mice was made successfully. Functionally, silencing of MYCL1 inhibited migration and invasion of the MGC-803 line in vitro and was accompanied with some ultrastructural changes. These results provide some evidences that lentiviral-mediated MYCL1 silencing may be a novel therapeutic strategy for the treatment of gastric cancer. SIGNIFICANCE OF THE STUDY: Gastric cancer is one of the most common malignant tumours worldwide and the second leading cause of cancer-related death in China. Our previous study revealed that expression of MYCL1 in gastric cancer tissue was associated with poor prognosis of patients. However, the potential underlying mechanism is still unclear. In the current study, we displayed the influence of MYCL1 gene on invasion and migration phenotype of gastric cancer cells and provided a possible explanation from the aspect of structural alteration. Our results suggested that downregulation of MYCL1 may be a potential therapeutic strategy for gastric cancer.

Measurement of volatile organic compounds and associated risk assessments through ingestion and dermal routes in Dongjiang Lake, China.

This study aims to investigate the occurrence, distribution and risk assessment of volatile organic compounds (VOCs) in Dongjiang Lake of China. Twenty two kinds of VOCs were detected, and the major VOCs were alkene compounds. The total concentration of VOCs (∑VOCs) ranged from 2.93 to 4.69 µg/L, and none of the VOCs detected in Dongjiang Lake exceeded the concentration limits set in the National Drinking Water Quality Standards (GB5749-2006) or the National Environmental Quality Standards for Surface Water (GB3838-2002) of China. Risk quotients (RQ) model, Multimedia Environment Pollutant Assessment System (MEPAS) and value of odor hazard index (OHI) were used to assess the ecological risk, lifetime carcinogenic risk and olfactory risk of VOCs in Dongjiang Lake, respectively. The RQtotal values varied from 3.95 × 10-3 to 0.34 and the RQ values for all the 22 detected VOCs in 12 sample locations of Dongjiang Lake were below 0.01, which means negligible risk to aquatic organisms. The cancerous and non-cancerous risk indices were in the range of 2.31 × 10-9-5.16 × 10-7 and 1.68 × 10-7-1.45 × 10-2, respectively. Bromodichloromethane and 1,1-dichloroethene were associated with the highest and lowest carcinogenic risks in all 12 sample locations. Results also demonstrated that the olfactory risk in Dongjiang Lake is negligible. These data suggest that the VOCs in Dongjiang Lake may not lead great ecological and health risks for organism and human.

Occurrence of typical antibiotics and source analysis based on PCA-MLR model in the East Dongting Lake, China.

The antibiotics residues in freshwater lakes are being highlighted around the world because of high potential threat to environment and human health. Understanding the current state of antibiotics and potential sources in lakes are important. The potential sources of antibiotics (Sewage treatment plants (STPs)), livestock and poultry farms and fishponds in the East Dongting was studied. Compared with other surface water bodies, the concentration of antibiotic in the East Dongting Lake was at a moderate or low level. Ten of 12 antibiotics likely originated from veterinary applications in livestock and poultry farms, especially in swine farms, and concentrations at these sources (ND-1240.41 ng L-1) were 1-3 orders of magnitude higher than in the effluent of local sewage treatment plants and fishponds. Based on a principal component analysis with multiple linear regression (PCA-MLR) model, we estimated source contributions of 79.95% for livestock and poultry farms, 0.27% for STPs, and 19.79% for aquaculture source and livestock and poultry farms. Overall, the predominance of sulfonamides and livestock and poultry farms in the East Dongting Lake has been identified, which can provide important information for regulating their veterinary use and environmental management.

[Physical fingerprint for quality control of Reduning injection].

The method of physical fingerprint spectrum for Reduning injection (RI) was proposed in this paper to improve its quality standards based on the strong correlation between physicochemical properties of drugs, their safety, effectiveness and stability. The quality of RI was studied by the thought and method of physical chemistry. The physical fingerprint spectrum was visually showed by the radar map, and consisted of eight indexes (pH, conductivity, turbidity, refractive index, osmolarity, surface tension, relative density, and kinematic viscosity). Then 12 batch of samples were verified. It was found that the physical fingerprint spectra of 3 batches of RI were in line with the standards within their validity time, with similarity above 0.999; in addition for the expired 9 batches of RI, their physical fingerprint spectra did not meet the standards. The results showed that physical fingerprint spectrum can be used for the quality control of RI, with a certain exemplary role in the quality evaluation of traditional Chinese medicine injection.

Diagnostic and prognostic role of serum protein peak at 6449 m/z in gastric adenocarcinoma based on mass spectrometry.

BACKGROUND: Gastric cancer (GC) is a highly aggressive cancer type associated with significant mortality owing to delayed diagnosis and non-specific symptoms observed in the early stages. Therefore, identification of novel specific GC serum biomarkers for screening purposes is an urgent clinical requirement. METHODS: This study recruited a total of 432 serum samples from 296 GC patients split into the mining and testing sets. We aimed to screen for reliable protein biomarkers from matched serum samples based on mass spectrometry, followed by comparison with three representative conventional markers using receiver operating characteristic and survival curve analyses to ascertain their potential values as diagnostic and prognostic biomarkers for GC. RESULTS: We identified an apoC-III fragment with confirmation in an independent test set from a second hospital. We found that the diagnostic ability of this fragment performed better than current standard GC diagnostic biomarkers both individually and in combination in distinguishing patients with GC from healthy individuals. Moreover, we found that this apoC-III protein fragment represents a more robust potential prognostic factor for GC than the three conventional markers. CONCLUSIONS: In view of these findings, we suggest that apoC-III protein fragment is a novel diagnostic and prognostic biomarker, a complement to conventional biomarkers in detecting GC.

[Early screening of developmental dysplasia of the hip among hospitalized children].

OBJECTIVE: To summarize retrospectively developmental dysplasia of the hip (DDH) screening of children within 36 months. METHODS: Newborn infants underwent initial DDH screening at First Affiliated Hospital, Zhengzhou University from September 2011 to May 2013. The examinations included double hip function, abduction test and Ortolani/Barlow test. After initial DDH screening, suspected and abnormal infants were transferred to our department for re-screening. And clinical physical examinations, type B ultrasound or radiological imaging were performed for confirmation or elimination. RESULTS: A total of 10 428 children were DDH screened. And 1 260 children were examined with ultrasound and 346 suspected and abnormal children (445 hips) were transferred for further assessments. Among them, 33 children (49 hips) were positive with Ortolani or Barlow test, 61 children (88 hips) had dysplasia of hip and 48 children (14 boys, 34 girls) (69 hips) received a final diagnosis of DDH. Left (n = 52) and right hip (n = 17) were involved with a disease incidence of DDH at 0.46%. CONCLUSIONS: Ultrasonic examination is both simple and cost-effective for DDH screening of children within 6 months. And meticulous medical examinations and imaging studies are effective DDH screening for children from 6 to 36 months.

Improved hypertensive stroke classification based on multi-scale feature fusion of head axial CT angiogram and multimodal learning.

PURPOSE: Strokes are severe cardiovascular and circulatory diseases with two main types: ischemic and hemorrhagic. Clinically, brain images such as computed tomography (CT) and computed tomography angiography (CTA) are widely used to recognize stroke types. However, few studies have combined imaging and clinical data to classify stroke or consider a factor as an Independent etiology. METHODS: In this work, we propose a classification model that automatically distinguishes stroke types with hypertension as an independent etiology based on brain imaging and clinical data. We first present a preprocessing workflow for head axial CT angiograms, including noise reduction and feature enhancement of the images, followed by an extraction of regions of interest. Next, we develop a multi-scale feature fusion model that combines the location information of position features and the semantic information of deep features. Furthermore, we integrate brain imaging with clinical information through a multimodal learning model to achieve more reliable results. RESULTS: Experimental results show our proposed models outperform state-of-the-art models on real imaging and clinical data, which reveals the potential of multimodal learning in brain disease diagnosis. CONCLUSION: The proposed methodologies can be extended to create AI-driven diagnostic assistance technology for categorizing strokes.

[Identification and expression of cytochrome C in tumor-bearing mice model with neuroblastoma].

OBJECTIVE: To screen, identify and verify the serum specific protein of neuroblastoma in a tumor-bearing murine model and speculate about the source of cytochrome C. METHODS: NB cells (KP-N-NS) were inoculated subcutaneously into nude mice. And the sera samples of tumor-bearing mice (observation group, n = 14) and controls (control group, n = 25) were collected at 4 weeks to screen for and identify differentially expressed proteins. The method of surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF-MS) was employed to screen the serum specific protein of neuroblastoma between two groups. Then serum protein targets were purified by high-performance liquid chromatography (HPLC) and identified by LC-MS/MS (LTQ). RESULTS: By comparing protein peaks among two sera groups, we identified the peak (11 609) showing significant differential expression between two groups. The expression of peak (11 609) was 3338.4 ± 1410.9 in observation group and 59.8 ± 40.7 in control group. This peak was identified as murine cytochrome C. CONCLUSION: Cytochrome C is a serum specific protein for neuroblastoma tumor and it comes from the apoptosis of non-tumor cells.

A self-training subspace clustering algorithm based on adaptive confidence for gene expression data.

Gene clustering is one of the important techniques to identify co-expressed gene groups from gene expression data, which provides a powerful tool for investigating functional relationships of genes in biological process. Self-training is a kind of important semi-supervised learning method and has exhibited good performance on gene clustering problem. However, the self-training process inevitably suffers from mislabeling, the accumulation of which will lead to the degradation of semi-supervised learning performance of gene expression data. To solve the problem, this paper proposes a self-training subspace clustering algorithm based on adaptive confidence for gene expression data (SSCAC), which combines the low-rank representation of gene expression data and adaptive adjustment of label confidence to better guide the partition of unlabeled data. The superiority of the proposed SSCAC algorithm is mainly reflected in the following aspects. 1) In order to improve the discriminative property of gene expression data, the low-rank representation with distance penalty is used to mine the potential subspace structure of data. 2) Considering the problem of mislabeling in self-training, a semi-supervised clustering objective function with label confidence is proposed, and a self-training subspace clustering framework is constructed on this basis. 3) In order to mitigate the negative impact of mislabeled data, an adaptive adjustment strategy based on gravitational search algorithm is proposed for label confidence. Compared with a variety of state-of-the-art unsupervised and semi-supervised learning algorithms, the SSCAC algorithm has demonstrated its superiority through extensive experiments on two benchmark gene expression datasets.

Gamma distribution based predicting model for breast cancer drug response based on multi-layer feature selection.

In the pursuit of precision medicine for cancer, a promising step is to predict drug response based on data mining, which can provide clinical decision support for cancer patients. Although some machine learning methods for predicting drug response from genomic data already exist, most of them focus on point prediction, which cannot reveal the distribution of predicted results. In this paper, we propose a three-layer feature selection combined with a gamma distribution based GLM and a two-layer feature selection combined with an ANN. The two regression methods are applied to the Encyclopedia of Cancer Cell Lines (CCLE) and the Cancer Drug Sensitivity Genomics (GDSC) datasets. Using ten-fold cross-validation, our methods achieve higher accuracy on anticancer drug response prediction compared to existing methods, with an R 2 and RMSE of 0.87 and 0.53, respectively. Through data validation, the significance of assessing the reliability of predictions by predicting confidence intervals and its role in personalized medicine are illustrated. The correlation analysis of the genes selected from the three layers of features also shows the effectiveness of our proposed methods.