Diphosphine Ligand-Enabled Nickel-Catalyzed Chelate-Assisted Inner-Selective Migratory Hydroarylation of Alkenes.

The precise control of the regioselectivity in the transition metal-catalyzed migratory hydrofunctionalization of alkenes remains a big challenge. With a transient ketimine directing group, the nickel-catalyzed migratory ß-selective hydroarylation and hydroalkenylation of alkenyl ketones has been realized with aryl boronic acids using alkyl halide as the mild hydride source for the first time. The key to this success is the use of a diphosphine ligand, which is capable of the generation of a Ni(II)-H species in the presence of alkyl bromide, and enabling the efficient migratory insertion of alkene into Ni(II)-H species and the sequent rapid chain walking process. The present approach diminishes organosilanes reductant, tolerates a wide array of complex functionalities with excellent regioselective control. Moreover, this catalytic system could also be applied to the migratory hydroarylation of alkenyl azahetereoarenes, thus providing a general approach for the preparation of 1,2-aryl heteroaryl motifs with wide potential applications in pharmaceutical discovery.

Network-based drug discovery by integrating systems biology and computational technologies.

Network-based intervention has been a trend of curing systemic diseases, but it relies on regimen optimization and valid multi-target actions of the drugs. The complex multi-component nature of medicinal herbs may serve as valuable resources for network-based multi-target drug discovery due to its potential treatment effects by synergy. Recently, robustness of multiple systems biology platforms shows powerful to uncover molecular mechanisms and connections between the drugs and their targeting dynamic network. However, optimization methods of drug combination are insufficient, owning to lacking of tighter integration across multiple '-omics' databases. The newly developed algorithm- or network-based computational models can tightly integrate '-omics' databases and optimize combinational regimens of drug development, which encourage using medicinal herbs to develop into new wave of network-based multi-target drugs. However, challenges on further integration across the databases of medicinal herbs with multiple system biology platforms for multi-target drug optimization remain to the uncertain reliability of individual data sets, width and depth and degree of standardization of herbal medicine. Standardization of the methodology and terminology of multiple system biology and herbal database would facilitate the integration. Enhance public accessible databases and the number of research using system biology platform on herbal medicine would be helpful. Further integration across various '-omics' platforms and computational tools would accelerate development of network-based drug discovery and network medicine.

Palladium-Catalyzed Hiyama-Type Coupling of Thianthrenium and Phenoxathiinium Salts.

Here, we demonstrate palladium-catalyzed Hiyama-type cross-coupling reactions of aryl thianthrenium or phenoxathiinium salts. By employing stable and inexpensive organosilanes, the arylation, alkenylation, and alkynylation were realized in high efficiency using commercially available Pd(tBu3P)2 as the catalyst, thus providing a reliable method for preparation of biaryls, styrenes, and aryl acetylenes with a broad functional group tolerance under mild conditions. Given the accessibility of aryl thianthrenium or phenoxathiinium salts from simple arenes in a remarkable regioselective fashion, this protocol also provides an attractive approach for the late-stage modification of complex bioactive scaffolds.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

[Challenges Regarding the Co-emission of Emerging Pollutants to Eco-environmental Monitoring and Management].

Emerging pollutants have drawn global concerns under rapid urbanization and industrialization. However, research has been relatively independent on specific groups of pollutants due to the limitation of the discipline. In this study, from the perspective of interdisciplinary research, taking the fluorochemical industry as an example, two major categories of emerging pollutants, per-and polyfluoroalkyl substances (PFAS) and ozone-depleting substances (ODS), were discussed regarding their co-emission. The co-production mechanism of the two types of pollutants were discussed from the production processes to reveal their internal relationship; their differences and cross-processes in the emission routes were analyzed, as well as the technical approaches and challenges required in sample collection, pretreatment, and instrumental analysis. The eco-environmental effects, including ecological and human health risks, ozone depletion, and global warming effects caused by the two types of pollutants in different media were comprehensively summarized. We also further expanded the perspectives of stakeholder analysis, life cycle analysis, and mass balance analysis to provide suggestions for further research and management of emerging pollutant co-emissions.

Clarifying the signal network of salvianolic acid B using proteomic assay and bioinformatic analysis.

Salvianolic acid B (SB) is a natural compound with protective effect against ischemia-reperfusion heart injury. However, the signal network of SB including both direct target proteins and downstream signal-related proteins has not been clarified. In the present study, epidermal growth factor receptor (EGFR) was predicted to be the most possible direct protein target of SB by INVDOCK, a ligand-protein inverse-docking algorithm. Possible signal-related proteins of SB in H9C2 cells, including both under normal condition and under ischemia-reperfusion injury, were searched using 2-DE analysis. Totally, 14 signal-related proteins were found. Finally, signal network from EGFR to the signal-related proteins was established using bioinformatic analysis. Interestingly, 9 of the 14 signal-related proteins could be included in a network together with EGFR through direct interaction or only one intermediate partner. The signal cascade from EGFR to heat shock protein 27 (HSP27) and mitofilin (IMMT, inner membrane mitochondrial protein) might be the most important cascade. The signal network was certified by measuring the binding affinity of SB to EGFR in vitro, the effect of SB on internalization and phosphorylation of EGFR, the effect of SB on viability and proliferation of H9C2 cells, and the expression of inner membrane mitochondrial protein in the presence of EGFR inhibitor AG 1478.

Case Report: A Rare Case of Nasal Forehead Mass in Kimura's Disease.

Background: Kimura's disease is a rheumatic immune disease and head and neck lymph nodes are often involved. A mass occurring in the nasal forehead is rare. Good prognosis after surgical resection by glucocorticoid therapy is more rare. Case Summary: We report the rare case of a nasal forehead mass in a 45-year-old male patient with Kimura's disease. The patient underwent resection of the mass in October 2018 in a local hospital and the postoperative pathology was unclear. He then underwent a second resection in our department in December 2019 mainly because growth of the mass was affecting his appearance. Postoperative pathology confirmed that the patient had Kimura's disease, and he accepted systemic treatment with prednisone. We followed the patient for 10 months after surgery. He is now recovering well and continues to be closely monitored during follow-up. Conclusion: It is rare that the painless mass in the nasal forehead is diagnosed as a Kimura's disease.After completely resection of the mass and systemic treatment with prednisone, the patient had a good outcome. We provide experience for the treatment of Kimura's disease in nasal forehead.

Difference between CD25+Tregs and Helios+Tregs in a murine model of allergic rhinitis.

INTRODUCTION: Regulatory T or Treg cells, balance the peripheral immune response to allergens in allergic rhinitis. Traditionally, Treg (CD25+ Treg) is identified by the coexpression of Foxp3 and CD25, but this strategy does not represent the true inhibitory function of Treg cells. Helios has been thought of as novel marker of activated Tregs, with an important inhibitory function. Consequently, Helios was proposed as a marker of Treg. Recent articles have shown that Foxp3 and Helios co-expression (Helios+Tregs) is an important functional stage of Treg. OBJECTIVE: To compare the prevalence of CD25+Tregs and Helios+Tregs using a mouse model of allergic rhinitis. METHODS: Twenty mice were randomized into two groups. The test group comprised 10 allergic rhinitis model mice exposed to ovalbumin; the control group was exposed to saline. The fractions of CD25+Tregs, Helios+Tregs, Helios+CD25+, and Helios+Foxp3+CD25+Tregs present in the two groups were determined using flow cytometry. RESULTS: CD25+Tregs and Helios+Tregs were less abundant in the spleen and nasal mucosa cells of the allergic rhinitis model compared with the control. We also observed fewer Helios+Tregs than CD25+Tregs in nasal mucosa and splenic cells of both control and test groups. Moreover, we observed fewer Helios+Foxp3+, Helios+CD25+, and Helios+Foxp3+CD25+ Tregs in the nasal mucosa in the allergic rhinitis model. Helios was expressed the most in CD4+ CD25+Foxp3+ T-cells, followed by CD4+ CD25-Foxp3- T-cells. Approximately 75% of CD25+Tregs were Helios+ in spleens of allergic rhinitis and control mice. CONCLUSION: This is the first report of the proportions of Helios+Tregs in nasal mucosa and spleens of allergic rhinitis mice. Gating true inhibitory Tregs with the coexpression of Foxp3 and Helios might be more useful than relying on the expression of CD25. This study provides a new insight for Treg studies of allergic rhinitis, and the potential utility of the marker as a therapeutic target.

Simulation of crosstalk between small GTPase RhoA and EGFR-ERK signaling pathway via MEKK1.

MOTIVATION: Small GTPase RhoA regulates cell-cycle progression via several mechanisms. Apart from its actions via ROCK, RhoA has recently been found to activate a scaffold protein MEKK1 known to promote ERK activation. We examined whether RhoA can substantially affect ERK activity via this MEKK1-mediated crosstalk between RhoA and EGFR-ERK pathway. By extending the published EGFR-ERK simulation models represented by ordinary differential equations, we developed a simulation model that includes this crosstalk, which was validated with a number of experimental findings and published simulation results. RESULTS: Our simulation suggested that, via this crosstalk, RhoA elevation substantially prolonged duration of ERK activation at both normal and reduced Ras levels. Our model suggests ERK may be activated in the absence of Ras. When Ras is overexpressed, RhoA elevation significantly prolongs duration of ERK activation but reduces the amount of active ERK partly due to competitive binding between ERK and RhoA to MEKK1. Our results indicated possible roles of RhoA in affecting ERK activities via MEKK1-mediated crosstalk, which seems to be supported by indications from several experimental studies that may also implicate the collective regulation of cell fate and progression of cancer and other diseases.

Proteomics characterization of the cytotoxicity mechanism of ganoderic acid D and computer-automated estimation of the possible drug target network.

Triterpenes isolated from Ganoderma lucidum could inhibit the growth of numerous cancer cell lines and were thought to be the basis of the anticancer effects of G. lucidum. Ganoderic acid D (GAD) is one of the major components in Ganoderma triterpenes. GAD treatment for 48 h inhibited the proliferation of HeLa human cervical carcinoma cells with an IC(50) value of 17.3 +/- 0.3 microM. Flow cytometric analysis and DNA fragmentation analysis indicated that GAD induced G(2)/M cell cycle arrest and apoptosis. To identify the cellular targets of GAD, two-dimensional gel electrophoresis was performed, and proteins altered in expressional level after GAD exposure of cells were identified by MALDI-TOF MS/MS. The regulation of proteins was also confirmed by Western blotting. The cytotoxic effect of GAD was associated with regulated expression of 21 proteins. Furthermore these possible GAD target-related proteins were evaluated by an in silico drug target searching program, INVDOCK. The INVDOCK analysis results suggested that GAD could bind six isoforms of 14-3-3 protein family, annexin A5, and aminopeptidase B. The direct binding affinity of GAD toward 14-3-3 zeta was confirmed in vitro using surface plasmon resonance biosensor analysis. In addition, the intensive study of functional association among these 21 proteins revealed that 14 of them were closely related in the protein-protein interaction network. They had been found to either interact with each other directly or associate with each other via only one intermediate protein from previous protein-protein interaction experimental results. When the network was expanded to a further interaction outward, all 21 proteins could be included into one network. In this way, the possible network associated with GAD target-related proteins was constructed, and the possible contribution of these proteins to the cytotoxicity of GAD is discussed in this report.

Osthole induces cell cycle arrest and apoptosis in head and neck squamous cell carcinoma by suppressing the PI3K/AKT signaling pathway.

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) is one of the most common lethal tumors with a high recurrence rate and low survival rate. Therefore, an urgent need exists for novel and effective treatment strategies for HNSCC patients. METHODS: Osthole, a natural ingredient extracted from Cnidium monnieri (L.) 'Cusson', has multiple pharmacological effects including antineoplastic activity. Regrettably, the antineoplastic effect of osthole in HNSCC cells remains undefined. We utilize in vitro assays to assess the anti-proliferative effects of osthole in HNSCC cells and tumorigenesis assays using FaDu cells in murine HNSCC models to assess in vivo function. Moreover, the possible molecular mechanisms of Osthole on HNSCC cells was also investigated. RESULTS: Our findings show that the anti-proliferation effect of osthole might function through induction of cell cycle arrest (G2/M phase) and apoptosis in HNSCC. Osthole could also down-regulating the protein level of cell cycle and apoptosis related proteins, such as Bcl-2, PARP1, Survivin, CyclinB1 and Cdc2, while up-regulating expression of Cleaved Caspase3/9, Cleaved PARP1 and Bax. Similarly, osthole suppressed the in vivo growth of FaDu cells in a subcutaneous tumor model. In terms of mechanism, our data show that osthole can suppress the PI3K/AKT pathway. CONCLUSIONS: In the current study, our in vitro and in vivo assay showed the suppressive effect of Osthole on HNSCC cells through induce cell cycle arrest (G2/M phase) and apoptosis. Moreover, the action mechanisms of Osthole on proliferation related signaling pathways was disclosed. Our present study suggests that osthole might be used as an effective therapeutic agent for patients with HNSCC.

Nonylphenol can aggravate allergic rhinitis in a murine model by regulating important Th cell subtypes and their associated cytokines.

Nonylphenol (NP) is a widely distributed, toxic endocrine-disrupting chemical exhibiting estrogenic activity. However, its effect on allergic rhinitis (AR) remains unclear. In this study, the effects of NP on a murine model of AR were investigated. Mice were divided into ovalbumin (OVA), NP, and control groups. OVA was used for sensitization and challenge. Mice in the NP group were administered NP during the sensitization period. Allergic nasal symptoms and eosinophil counts in nasal mucosa were measured. Serum levels of OVA-specific IgE were determined by enzyme-linked immunosorbent assay. The mRNA levels of transcription factors of Th cells were determined with real-time polymerase chain reaction. Th cell subtypes and Treg numbers were counted with the aid of multi-color flow cytometry. Cytokine concentrations in nasal mucosa were determined using the cytometric bead array method. Subcutaneous injection of NP into mice exhibiting AR enhanced not only the nasal allergic symptoms, but also eosinophil infiltration and OVA-specific IgE. Moreover, NP upregulated IL-4, IL-5, IL-13, IL-9, IL-6 and IL-17, and downregulated IL-10, in the AR mouse model; IFN-γ and IL-23 were not affected. Transcription factors and Th cell percentages were evaluated to determine whether NP regulates Th cell subtypes in an AR mouse model. GATA3, PU.1, and RORγt levels were significantly increased, but FoxP3 and Helios were decreased. In addition, Th2, Th9, and Th17 subtype percentages significantly increased, and Treg cell percentages decreased, in NP administration groups; the percentage of Th1 subtypes was not affected. NP enhanced allergic inflammation in the AR mouse model through upregulation of Th2, Th9, and Th17 responses and negative regulation of Treg responses. These results suggest that NP may be trigger AR.

Computer-aided identification of protein targets of four polyphenols in Alzheimer's disease (AD) and validation in a mouse AD model.

Natural polyphenols are a large class of phytochemicals with neuroprotective effects. Four polyphenolic compounds: hesperidin, icariin, dihydromyricetin and baicalin were selected to evaluate their effects on Alzheimer's disease (AD). We analyzed by an inverse docking procedure (INVDOCK) the potential protein targets of these polyphenols within the KEGG AD pathway. Consequently, their therapeutic effects were evaluated and compared in a transgenic APP/PS1 mouse model of AD. These polyphenols were docked to several targets, including APP, BACE, PSEN, IDE, CASP, calpain and TNF-α, suggesting potential in vivo activities. Five month old transgenic mice were treated with these polyphenols. Icariin and hesperidin restored behavioral deficits and ameliorated Aß deposits in both the cortex and hippocampus while baicalin and dihydromyricetin showed no substantial effects. Our findings suggest that hesperidin and icariin could be considered potential therapeutic candidates of human AD.

Computer prediction of allergen proteins from sequence-derived protein structural and physicochemical properties.

BACKGROUND: Computational methods have been developed for predicting allergen proteins from sequence segments that show identity, homology, or motif match to a known allergen. These methods achieve good prediction accuracies, but are less effective for novel proteins with no similarity to any known allergen. METHODS: This work tests the feasibility of using a statistical learning method, support vector machines, as such a method. The prediction system is trained and tested by using 1005 allergen proteins from the Allergome database and 22,469 non-allergen proteins from 7871 Pfam families. RESULTS: Testing results by an independent set of 229 allergen and 6717 non-allergen proteins from 7871 Pfam families show that 93.0% and 99.9% of these are correctly predicted, which are comparable to the best results of other methods. Of the 18 novel allergen proteins non-homologous to any other proteins in the Swissprot database, 88.9% is correctly predicted. A further screening of 168,128 proteins in the Swissprot database finds that 2.9% of the proteins are predicted as allergen proteins, which is consistent with the estimated numbers from motif-based methods. CONCLUSIONS: Our study suggests that SVM is a potentially useful method for predicting allergen proteins and it has certain capability for predicting novel allergen proteins. Our software can be accessed at .

Modular co-evolution of metabolic networks.

BACKGROUND: The architecture of biological networks has been reported to exhibit high level of modularity, and to some extent, topological modules of networks overlap with known functional modules. However, how the modular topology of the molecular network affects the evolution of its member proteins remains unclear. RESULTS: In this work, the functional and evolutionary modularity of Homo sapiens (H. sapiens) metabolic network were investigated from a topological point of view. Network decomposition shows that the metabolic network is organized in a highly modular core-periphery way, in which the core modules are tightly linked together and perform basic metabolism functions, whereas the periphery modules only interact with few modules and accomplish relatively independent and specialized functions. Moreover, over half of the modules exhibit co-evolutionary feature and belong to specific evolutionary ages. Peripheral modules tend to evolve more cohesively and faster than core modules do. CONCLUSION: The correlation between functional, evolutionary and topological modularity suggests that the evolutionary history and functional requirements of metabolic systems have been imprinted in the architecture of metabolic networks. Such systems level analysis could demonstrate how the evolution of genes may be placed in a genome-scale network context, giving a novel perspective on molecular evolution.

Are herb-pairs of traditional Chinese medicine distinguishable from others? Pattern analysis and artificial intelligence classification study of traditionally defined herbal properties.

Multi-herb prescriptions of traditional Chinese medicine (TCM) often include special herb-pairs for mutual enhancement, assistance, and restraint. These TCM herb-pairs have been assembled and interpreted based on traditionally defined herbal properties (TCM-HPs) without knowledge of mechanism of their assumed synergy. While these mechanisms are yet to be determined, properties of TCM herb-pairs can be investigated to determine if they exhibit features consistent with their claimed unique synergistic combinations. We analyzed distribution patterns of TCM-HPs of TCM herb-pairs to detect signs indicative of possible synergy and used artificial intelligence (AI) methods to examine whether combination of their TCM-HPs are distinguishable from those of non-TCM herb-pairs assembled by random combinations and by modification of known TCM herb-pairs. Patterns of the majority of 394 known TCM herb-pairs were found to exhibit signs of herb-pair correlation. Three AI systems, trained and tested by using 394 TCM herb-pairs and 2470 non-TCM herb-pairs, correctly classified 72.1-87.9% of TCM herb-pairs and 91.6-97.6% of the non-TCM herb-pairs. The best AI system predicted 96.3% of the 27 known non-TCM herb-pairs and 99.7% of the other 1,065,100 possible herb-pairs as non-TCM herb-pairs. Our studies suggest that TCM-HPs of known TCM herb-pairs contain features distinguishable from those of non-TCM herb-pairs consistent with their claimed synergistic or modulating combinations.

Neutralization of interleukin-9 ameliorates symptoms of allergic rhinitis by reducing Th2, Th9, and Th17 responses and increasing the Treg response in a murine model.

A novel independent Th-cell subset, characterized by high expression of interleukin (IL)-9, has been recognized as the "Th9" subset. Although Th9 cells are important in many diseases, their contribution to allergic rhinitis (AR) remains unclear. We therefore first determined whether Th9 cells were present in a mouse model of AR. We then investigated the their involvement in the distribution of CD4+ T-cell subsets and the symptoms of AR by treating mice with anti-IL-9 antibodies (Abs). Anti-IL-9 Abs were administered intranasally during rechallenge of ovalbumin (OVA)-induced AR in BALB/c mice. We measured nasal rubbing motion, sneezing and eosinophils, as well as the Th1 (Th1 cell percentage, Ifn-γ mRNA/protein, T-bet mRNA), Th2 (Th2 cell percentage, Il-4 mRNA/protein, Gata3 mRNA), Th9 (Th9 cell percentages Il-9 mRNA/protein, PU.1 and Irf4 mRNA), Th17 (Th17 cell percentage, Il-17 mRNA/protein, Rorγt mRNA), and Treg (Treg cell percentage, Foxp3 mRNA) responses in the nasal mucosa. Treatment with anti-IL-9 Abs markedly reduced nasal rubbing, sneezing, eosinophil infiltration, and Th2, Th9, and Th17 responses, and increased the Treg response. Our findings emphasize the importance of IL-9/Th9 in the pathogenesis of AR, and suggest that anti-IL-9 Ab treatment may be an effective therapeutic strategy for AR.

Neutralization of interleukin-17 suppresses allergic rhinitis symptoms by downregulating Th2 and Th17 responses and upregulating the Treg response.

Allergic rhinitis (AR) has long been considered to predominantly involve the actions of Th2 cells, with relatively small contributions from Th1 cells. In recent years, the discovery of Th17 and regulatory T (Treg) cells has rendered the Th1/Th2 balance paradigm more complex and expanded our understanding of the pathogenesis of AR. IL-17, a key cytokine produced by Th17 cells, is known to induce allergen-specific Th2 cell activation, eosinophil and neutrophil accumulation, and serum IgE production in asthma; all of these features may play important roles in AR. To the best of our knowledge, only a few studies have assessed the feasibility of using IL-17 antagonists to treat AR. Thus, the principal objectives of the present study were, first, to determine the status of Th17 and Treg cells in the nasal mucosa of a mouse model of AR, and, second, to investigate the effects of IL-17 on such cells and the therapeutic efficacy of anti-IL-17 antibodies (Abs) in the context of AR. Anti-IL-17 Abs were given intranasally during the re-challenge of BALB/c mice with ovalbumin (OVA)-induced AR. We measured the numbers of nasal rubbing motions and sneezes, eosinophil and neutrophil levels, Th1, Th2, Th17, and Treg parameters in the nasal mucosa. Anti-IL-17 Abs markedly reduced the number of nasal rubbing motions and sneezes, decreased eosinophil and neutrophil infiltration, reduced Th2 and Th17 responses, and increased the Treg response. Anti-IL-17 Ab treatment protects against AR. These results will improve our understanding of AR pathogenesis and may lead to the development of novel therapeutic approaches for management of the condition.

Key symptoms selection for two major syndromes diagnosis of Chinese medicine in chronic hepatitis B.

OBJECTIVE: To identify key symptoms of two major syndromes in chronic hepatitis B (CHB), which can be the clinical evidence for Chinese medicine (CM) doctors to make decisions. METHODS: Standardization scales on diagnosis for CHB in CM were designed including physical symptoms, tongue and pulse appearance. The total of 695 CHB cases with dampness-heat (DH) syndrome or Pi (Spleen) deficiency (SD) syndrome were collected for feature selection and modeling, another 275 CHB patients were collected in different locations for validation. Key symptoms were selected based on modified information gain (IG), and 5 classifiers were applied to assist with models training and validation. Classification accuracy and area under receiver operating characteristic curves (AUC) were evaluated. RESULTS: (1) Thirteen DH syndrome key symptoms and 13 SD syndrome key symptoms were selected from original 125 symptoms; (2) The key symptoms could achieve similar or better diagnostic accuracy than the original total symptoms; (3) In the validation phase, the key symptoms could identify syndromes effectively, especially in DH syndrome, which average prediction accuracy on 5 classifiers could achieve 0.864 with the average AUC 0.772. CONCLUSION: The selected key symptoms could be simple DH and SD syndromes diagnostic elements applied in clinical directly. (Registration N0.: ChiCTR-DCC-10000759).

Hierarchical modularity of nested bow-ties in metabolic networks.

BACKGROUND: The exploration of the structural topology and the organizing principles of genome-based large-scale metabolic networks is essential for studying possible relations between structure and functionality of metabolic networks. Topological analysis of graph models has often been applied to study the structural characteristics of complex metabolic networks. RESULTS: In this work, metabolic networks of 75 organisms were investigated from a topological point of view. Network decomposition of three microbes (Escherichia coli, Aeropyrum pernix and Saccharomyces cerevisiae) shows that almost all of the sub-networks exhibit a highly modularized bow-tie topological pattern similar to that of the global metabolic networks. Moreover, these small bow-ties are hierarchically nested into larger ones and collectively integrated into a large metabolic network, and important features of this modularity are not observed in the random shuffled network. In addition, such a bow-tie pattern appears to be present in certain chemically isolated functional modules and spatially separated modules including carbohydrate metabolism, cytosol and mitochondrion respectively. CONCLUSION: The highly modularized bow-tie pattern is present at different levels and scales, and in different chemical and spatial modules of metabolic networks, which is likely the result of the evolutionary process rather than a random accident. Identification and analysis of such a pattern is helpful for understanding the design principles and facilitate the modelling of metabolic networks.