Electronic Preresonance Stimulated Raman Scattering Spectromicroscopy Using Multiple-Plate Continuum.

Stimulated Raman scattering (SRS) spectromicroscopy is a powerful technique that enables label-free detection of chemical bonds with high specificity. However, the low Raman cross section due to typical far-electronic resonance excitation seriously restricts the sensitivity and undermines its application to bio-imaging. To address this bottleneck, the electronic preresonance (EPR) SRS technique has been developed to enhance the Raman signals by shifting the excitation frequency toward the molecular absorption. A fundamental weakness of the previous demonstration is the lack of dual-wavelength tunability, making EPR-SRS only applicable to a limited number of species in the proof-of-concept experiment. Here, we demonstrate the EPR-SRS spectromicroscopy using a multiple-plate continuum (MPC) light source able to examine a single vibration mode with independently adjustable pump and Stokes wavelengths. In our experiments, the C═C vibration mode of Alexa 635 is interrogated by continuously scanning the pump-to-absorption frequency detuning throughout the entire EPR region enabled by MPC. The results exhibit 150-fold SRS signal enhancement and good agreement with the Albrecht A-term preresonance model. Signal enhancement is also observed in EPR-SRS images of the whole Drosophila brain stained with Alexa 635. With the improved sensitivity and potential to implement hyperspectral measurement, we envision that MPC-EPR-SRS spectromicroscopy can bring the Raman techniques closer to a routine in bio-imaging.

Baseline Pydiflumetofen Sensitivity of Fusarium pseudograminearum Isolates Collected from Henan, China, and Potential Resistance Mechanisms.

Fusarium crown rot (FCR), caused by Fusarium pseudograminearum, is one of the most important diseases impacting wheat production in the Huanghuai region, the most important wheat-growing region of China. The current study found that the SDHI fungicide pydiflumetofen, which was recently developed by Syngenta Crop Protection, provided effective control of 67 wild-type F. pseudograminearum isolates in potato dextrose agar, with an average EC50 value of 0.060 ± 0.0098 µg/ml (SE). Further investigation revealed that the risk of fungicide resistance in pydiflumetofen was medium to high. Four F. pseudograminearum mutants generated by repeated exposure to pydiflumetofen under laboratory conditions indicated that pydiflumetofen resistance was associated with fitness penalties. Mutants exhibited significantly (P < 0.05) reduced sporulation in mung bean broth and significantly (P < 0.05) reduced pathogenicity in wheat seedlings. Sequence analysis indicated that the observed pydiflumetofen resistance of the mutants was likely associated with amino acid changes in the different subunits of the succinate dehydrogenase target protein, including R18L and V160M substitutions in the FpSdhA sequence; D69V, D147G, and C257R in FpSdhB; and W78R in FpSdhC. This study found no evidence of cross-resistance between pydiflumetofen and the alternative fungicides tebuconazole, fludioxonil, carbendazim, or fluazinam, which all have distinct modes of action and could therefore be used in combination or rotation with pydiflumetofen to reduce the risk of resistance emerging in the field. Taken together, these results indicate that pydiflumetofen has potential as a novel fungicide for the control of FCR caused by F. pseudograminearum and could therefore be of great significance in ensuring high and stable wheat yields in China.

Identification of a Novel Streptomyces sp. Strain HU2014 Showing Growth Promotion and Biocontrol Effect Against Rhizoctonia spp. in Wheat.

Wheat sharp eyespot is a serious disease caused by the phytopathogens Rhizoctonia cerealis and R. solani. Some species in the genus Streptomyces have been identified as potential biocontrol agents against phytopathogens. In this investigation, the physiological, biochemical, phylogenetic, and genomic characteristics of strain HU2014 indicate that it is a novel Streptomyces sp. most closely related to Streptomyces albireticuli. Strain HU2014 exhibited strong antifungal activity against R. cerealis G11 and R. solani YL-3. Ultraperformance liquid chromatography-mass spectrometry on the four extracts from the extracellular filtrate of strain HU2014 identified 10 chemical constituents in the Natural Products Atlas with high match levels (more than 90%). In an antifungal efficiency test on wheat sharp eyespot, two extracts significantly reduced the lesion areas on bean leaves infected by R. solani YL-3. The drenching of wheat in pots with spore suspension of strain HU2014 demonstrated a control efficiency of 65.1% against R. cerealis G11 (compared with 66.9% when treated by a 30% hymexazol aqueous solution). Additionally, in vitro and pot experiments demonstrated that strain HU2014 can produce indoleacetic acid, siderophores, extracellular enzymes, and solubilized phosphate, and it can promote plant growth. We conclude that strain HU2014 could be a valuable microbial resource for growth promotion of wheat and biological control of wheat sharp eyespot.

Analgesic Effectiveness of Dinalbuphine Sebacate in Video-Assisted Thoracoscopic Wedge Resection and Its Effect on Reducing Postoperative Pulmonary Complications: A Retrospective Cohort Study.

BACKGROUND: Inadequate postoperative analgesia may cause postoperative complications, such as pulmonary complications. This study evaluated the analgesic effectiveness of a single preoperative injection of dinalbuphine sebacate (DS) in patients undergoing video-assisted thoracoscopic wedge resection and assessed whether it can reduce the incidence of postoperative pulmonary complications (PPCs). METHODS: In this study, the data of 757 patients who underwent VATS wedge resection at a medical center were retrospectively reviewed. The patients were divided into the DS group and the conventional analgesia (CA) group. The following parameters were analyzed: analgesic consumption during hospitalization, the incidence of PPCs, and the postoperative use of oxygen therapy. RESULTS: Compared with the CA group, the DS group had lower nalbuphine, tramadol, parecoxib, acetaminophen, diclofenac, and utraphen consumption during the postoperative period; higher morphine and ketorolac consumption; and comparable fentanyl consumption. Nonetheless, the frequency of requesting pain relief was significantly lower in the DS group. No significant between-group differences were noted in the incidence of PPCs. However, the DS group had fewer requirements for oxygen therapy in the ward, early removal of chest tubes, and shorter length of hospital stay. CONCLUSION: A single preoperative injection of DS reduced the frequency of salvage analgesic administration and total consumption of certain postoperative analgesics, suggesting the effective pain relief of DS, and it did not increase the incidence of PPCs. Additionally, it reduced the need for postoperative oxygen therapy, which may suggest a better prognosis and smoother postoperative pulmonary recovery for patients.

Baseline Sensitivity and Potential Resistance Mechanisms for Fusarium pseudograminearum to Fludioxonil.

Fusarium crown rot (FCR), which is caused by Fusarium pseudograminearum, is one of the most important diseases affecting wheat production in the Huanghuai wheat-growing region of China. Although the phenylpyrrole fungicide fludioxonil is known to have a broad-spectrum activity against a wide range of plant pathogens, including F. pseudograminearum, it has not yet been registered for the control of FCR in China, and further research is needed to assess the biological characteristics and molecular mechanisms associated with fludioxonil resistance, and especially the potential for highly resistant isolates to emerge. The current study demonstrated that the baseline fludioxonil sensitivity of 61 F. pseudograminearum isolates collected from the Henan province of China during the summers of 2019 to 2021 conformed to a unimodal distribution with a mean effective concentration for 50% inhibition (EC50) value of 0.021 ± 0.003 µg/ml, which indicated that none of the isolates exhibited natural resistance to fludioxonil. Nevertheless, four fludioxonil-resistant mutants were attained after repeated exposure to fludioxonil under laboratory conditions. All resistant mutants exhibited significantly lower growth rates on potato dextrose agar (PDA) and lower levels of sporulation and pathogenicity in wheat seedlings. In addition, the resistant mutants also exhibited less growth on PDA amended with either 0.5 M mannitol, 0.5 M glucose, 0.5 M MgCl2, or 0.5 M NaCl, which indicated that they had greater sensitivity to osmotic stress. Molecular analysis of the proposed fludioxonil target protein FpOs1 indicated that the predicted sequences of the resistant mutants contained none of the characteristic amino acid changes previously associated with fludioxonil resistance in other species. Further investigation via quantitative real-time PCR analysis revealed that expression of the FpOs1 gene was significantly altered in the resistant mutants in both the absence and presence of fludioxonil. Meanwhile, plate assays found evidence of cross-resistance between fludioxonil and cyprodinil, as well as with the triazole fungicides tebuconazole and difenoconazole, but not with other commonly used fungicides including prochloraz, fluazinam, and carbendazim. Taken together, these results provide new insights into the mechanism and biological characteristics associated with fludioxonil resistance in F. pseudograminearum and indicate that fludioxonil could provide effective and sustained control of FCR during wheat production.

Mechanism of Pydiflumetofen Resistance in Fusarium graminearum in China.

Fusarium head blight (FHB), which is primarily caused by Fusarium graminearum, is a widespread and devastating disease of wheat. In the absence of resistant varieties, the control of FHB relies heavily on the application of fungicides, and the new generation SDHI fungicide, pydiflumetofen, has recently been registered in China for the control of FHB in wheat. The current study explored three genetically stable, highly resistant laboratory mutants (S2-4-2R, S27-3R, and S28-2R, with EC50 values of 25.10, 28.57, and 19.22 µg/mL, respectively) to investigate the potential risks associated with pydiflumetofen resistance. Although the mycelial growth of the mutants differed little compared to their parental isolates, the study found that the resistant mutants exhibited significantly reduced (p < 0.05) levels of sporulation and pathogenicity, which suggests a significant fitness cost associated with pydiflumetofen resistance in F. graminearum. Sequence analysis of the Sdh target protein identified numerous amino acid substitutions in the predicted sequences of the four subunits: FgSdhA, FgSdhB, FgSdhC, and FgSdhD. Indeed, the mutants were found to have a series of substitution in multiple subunits such that all three exhibited five identical changes, including Y182F in the FgSdhA subunit; H53Q, C90S, and A94V in FgSdhB; and S31F in FgSdhC. In addition, gene expression analysis revealed that all of the FgSdh genes had significantly altered expression (p < 0.05), particularly FgSdhA and FgdhC, which exhibited remarkably low levels of expression. However, the study found no evidence of cross-resistance between pydiflumetofen and tebuconazole, fludioxonil, prochloraz, fluazinam, carbendazim, pyraclostrobin, or difenoconazole, which indicates that these fungicides, either in rotation or combination with pydiflumetofen, could mitigate the risk of resistance emerging and provide ongoing control of FHB to ensure high and stable wheat yields.

Practice in Information Technology Support for Fangcang Shelter Hospital during COVID-19 Epidemic in Wuhan, China.

In confronting the sudden epidemic of COVID-19, China and other countries have been under great deal of pressure to block virus transmission and reduce death cases. Fangcang shelter hospital, which is converted from large-scale public venue, is proposed and proven to be an effective way for administering medical care and social isolation. This paper presents the practice in information technology support for a Fangcang shelter hospital in Wuhan, China. The experiences include the deployment strategy of IT infrastructure, the redesign of function modules in the hospital information system (HIS), equipment maintenance and medical staff training. The deployment strategy and HIS modules have ensured smoothness and efficiency of clinical work. The team established a quick response mechanism and adhered to the principle of nosocomial infection control. Deployment of network and modification of HIS was finished in the 48 hours before patient admittance. A repair hotline and remote support for equipment and software were available whenever medical workers met with any questions. No engineer ever entered the contaminated areas and no one was infected by the coronavirus during the hospital operation. Up to now, Fangcang shelter hospital is adopted by many regions around the world facing the collapse of their medical systems. This valuable experience in informatization construction and service in Wuhan may help participators involving in Fangcang shelter hospital get better information technology support, and find more practical interventions to fight the epidemic.

Protein tyrosine phosphatase L1 represses endothelial-mesenchymal transition by inhibiting IL-1ß/NF-κB/Snail signaling.

Endothelial-mesenchymal transition (EnMT) plays a pivotal role in various diseases, including pulmonary hypertension (PH), and transcription factors like Snail are key regulators of EnMT. In this study we investigated how these factors were regulated by PH risk factors (e.g. inflammation and hypoxia) in human umbilical vein endothelial cells (HUVECs). We showed that treatment with interleukin 1ß (IL-1ß) induced EnMT of HUVECs via activation of NF-κB/Snail pathway, which was further exacerbated by knockdown of protein tyrosine phosphatase L1 (PTPL1). We demonstrated that PTPL1 inhibited NF-κB/Snail through dephosphorylating and stabilizing IκBα. IL-1ß or hypoxia could downregulate PTPL1 expression in HUVECs. The deregulation of PTPL1/NF-κB signaling was validated in a monocrotaline-induced rat PH (MCT-PH) model and clinical PH specimens. Our findings provide novel insights into the regulatory mechanisms of EnMT, and have implications for identifying new therapeutic targets for clinical PH.

Biological Characteristics and Molecular Mechanism of Fludioxonil Resistance in Botrytis cinerea From Henan Province of China.

The gray mold caused by Botrytis cinerea has a significant impact on tomato production throughout the world. Although the synthetic fungicide fludioxonil can effectively control B. cinerea, there have been several reports of resistance to this fungicide. This study indicated that all of the fludioxonil-resistant strains tested, including one field-resistant isolate and four laboratory strains, had reduced fitness relative to sensitive isolates. In addition to having reduced growth, sporulation, and pathogenicity, the resistant strains were more sensitive to osmotic stress and had significantly (P < 0.05) higher peroxidase activity. BOs1, a kinase in the high-osmolarity glycerol stress response signal transduction pathway, is believed to harbor mutations related to fludioxonil resistance. Sequence analysis of their BOs1 sequences indicated that the fludioxonil-resistant field isolate, XXtom1806, had four point mutations resulting in four amino acid changes (I365S, S531G, T565N, and T1267A) and three amino acids (I365S, S531G, and T565N) in the histidine kinases, adenylyl cyclases, methyl-accepting chemotaxis receptors, and phosphatases domain, which associated with fludioxonil binding. Similarly, two of the laboratory strains, XXtom-Lab1 and XXtom-Lab4, had three (Q846S, I1126S, and G415D) and two (P1051S and V1241M) point mutations, respectively. A third strain, XXtom-lab3, had a 52-bp insertion that included a stop codon at amino acid 256. Interestingly, the BOs1 sequence of the fourth laboratory strain, XXtom-lab5, was identical to those of the sensitive isolates, indicating that an alternative resistance mechanism exists. The study also found evidence of positive cross-resistance between fludioxonil and the dicarboximide fungicides procymidone and iprodione, but no cross-resistance was detected with any other fungicides tested, including boscalid, carbendazim, tebuconazole, and fluazinam.

The clinical characteristics and prognosis of ABPA are closely related to the mucus plugs in central bronchiectasis.

INTRODUCTION: The characteristics of Allergic Bronchopulmonary Aspergillosis (ABPA) based on its radiological classification is still unclear. OBJECTIVES: To investigate the clinical significances of ABPA patients with central bronchiectasis (ABPA-CB) by different radiological classifications of mucus plugs. METHODS: ABPA-CB patients from a pulmonary hospital between 2008 and 2015 were retrospectively included and analysed. According to the chest imaging in their first visit to physician, the ABPA-CB patients were divided into two groups based on the presence of high-attenuation mucus (HAM) or low-attenuation mucus (LAM). The primary endpoint was ABPA relapse within 1 year since the glucocorticoid withdrawal. The relationship between the imaging findings and the clinical prognosis was illuminated. RESULTS: A total of 125 ABPA patients were analysed in this study. Compared to the LAM group, the HAM group presented higher blood eosinophil cells counts, higher rates of Aspergillus detection isolated in sputum and expectoration of brownish-black mucus plugs, more affected lobes and segments, poorer pulmonary function and higher rate of relapse. CONCLUSIONS: The clinical characteristics and prognosis of ABPA-CB patients are closely related to its radiological phenotype of mucus plugs in the central bronchiectasis. Clinicians should promote a diversity of personalized treatments for different patients with different radiological characteristics.

NAA at a high concentration promotes efficient plant regeneration via direct somatic embryogenesis and SE-mediated transformation system in Ranunculus sceleratus.

The novel methods for efficient plant regeneration via direct somatic embryogenesis (SE) and SE-mediated transformation system under high concentration of NAA in Ranunculus sceleratus were established. On MS media containing a high concentration of NAA (10.0 mg/L) in the dark, all inoculated explants (root, stem and leaf) formed somatic embryos at high frequencies, respectively, 66.03, 126.47 and 213.63 embryoids per explant, and 100% of the embryoids developed into plantlets on 1/2 MS rooting media. Morphological and histological analyses revealed that SE in R. sceleratus followed a classical pattern. All inoculated explants can be used as receptors for genetic transformation in R. sceleratus, through direct SE-mediated method after Agrobacterium infection. RcLEC1-B, as a marker gene, changed the number and morphology of flower organs and the development of cuticle in R. sceleratus, which indicated that the efficient transgenic system of R. sceleratus was established. To our knowledge, this is the first observation that both direct SE and transgenic transformation system, via induction of a single plant growth regulator, have been successfully constructed in R. sceleratus.

Investigation mechanisms between normal, developing and regenerating livers for regenerative liver drug design.

Aim: A systematic multimolecule drug design procedure is proposed for promoting hepatogenesis and liver regeneration. Materials & methods: Genome-wide microarray data including three hepatic conditions are obtained from the GEO database (GSE15238). System modeling and big data mining methods are used to construct real genome-wide genetic-and-epigenetic networks (GWGENs). Then, we extracted the core GWGENs by applying principal network projection on real GWGENs of normal, developing and regenerating livers, respectively. After that, we investigated the significant signal pathways and epigenetic modifications in the core GWGENs to identify potential biomarkers as drug targets. Result & conclusion: A multimolecule drug consisting of sulmazole, clofibrate, colchicine, furazolidone, nadolol, eticlopride and felbinac is proposed to target on novel biomarkers for promoting hepatogenesis and liver regeneration.

Comparing progression molecular mechanisms between lung adenocarcinoma and lung squamous cell carcinoma based on genetic and epigenetic networks: big data mining and genome-wide systems identification.

Non-small-cell lung cancer (NSCLC) is the predominant type of lung cancer in the world. Lung adenocarcinoma (LADC) and lung squamous cell carcinoma (LSCC) are subtypes of NSCLC. We usually regard them as different disease due to their unique molecular characteristics, distinct cells of origin and dissimilar clinical response. However, the differences of genetic and epigenetic progression mechanism between LADC and LSCC are complicated to analyze. Therefore, we applied systems biology approaches and big databases mining to construct genetic and epigenetic networks (GENs) with next-generation sequencing data of LADC and LSCC. In order to obtain the real GENs, system identification and system order detection are conducted on gene regulatory networks (GRNs) and protein-protein interaction networks (PPINs) for each stage of LADC and LSCC. The core GENs were extracted via principal network projection (PNP). Based on the ranking of projection values, we got the core pathways in respect of KEGG pathway. Compared with the core pathways, we found significant differences between microenvironments, dysregulations of miRNAs, epigenetic modifications on certain signaling transduction proteins and target genes in each stage of LADC and LSCC. Finally, we proposed six genetic and epigenetic multiple-molecule drugs to target essential biomarkers in each progression stage of LADC and LSCC, respectively.

Systems Biology Approaches to Investigate Genetic and Epigenetic Molecular Progression Mechanisms for Identifying Gene Expression Signatures in Papillary Thyroid Cancer.

Thyroid cancer is the most common endocrine cancer. Particularly, papillary thyroid cancer (PTC) accounts for the highest proportion of thyroid cancer. Up to now, there are few researches discussing the pathogenesis and progression mechanisms of PTC from the viewpoint of systems biology approaches. In this study, first we constructed the candidate genetic and epigenetic network (GEN) consisting of candidate protein-protein interaction network (PPIN) and candidate gene regulatory network (GRN) by big database mining. Secondly, system identification and system order detection methods were applied to prune candidate GEN via next-generation sequencing (NGS) and DNA methylation profiles to obtain the real GEN. After that, we extracted core GENs from real GENs by the principal network projection (PNP) method. To investigate the pathogenic and progression mechanisms in each stage of PTC, core GEN was denoted in respect of KEGG pathways. Finally, by comparing two successive core signaling pathways of PTC, we not only shed light on the causes of PTC progression, but also identified essential biomarkers with specific gene expression signature. Moreover, based on the identified gene expression signature, we suggested potential candidate drugs to prevent the progression of PTC with querying Connectivity Map (CMap).

Investigating Pathogenic and Hepatocarcinogenic Mechanisms from Normal Liver to HCC by Constructing Genetic and Epigenetic Networks via Big Genetic and Epigenetic Data Mining and Genome-Wide NGS Data Identification.

The prevalence of hepatocellular carcinoma (HCC) is still high worldwide because liver diseases could develop into HCC. Recent reports indicate nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NAFLD&NASH) and primary biliary cirrhosis and primary sclerosing cholangitis (PBC&PSC) are significant of HCC. Therefore, understanding the cellular mechanisms of the pathogenesis and hepatocarcinogenesis from normal liver cells to HCC through NAFLD&NASH or PBC&PSC is a priority to prevent the progression of liver damage and reduce the risk of further complications. By the genetic and epigenetic data mining and the system identification through next-generation sequencing data and its corresponding DNA methylation profiles of liver cells in normal, NAFLD&NASH, PBC&PSC, and HCC patients, we identified the genome-wide real genetic and epigenetic networks (GENs) of normal, NAFLD&NASH, PBC&PSC, and HCC patients. In order to get valuable insight into these identified genome-wide GENs, we then applied a principal network projection method to extract the corresponding core GENs for normal liver cells, NAFLD&NASH, PBC&PSC, and HCC. By comparing the signal transduction pathways involved in the identified core GENs, we found that the hepatocarcinogenesis through NAFLD&NASH was induced through DNA methylation of HIST2H2BE, HSPB1, RPL30, and ALDOB and the regulation of miR-21 and miR-122, and the hepatocarcinogenesis through PBC&PSC was induced through DNA methylation of RPL23A, HIST2H2BE, TIMP1, IGF2, RPL30, and ALDOB and the regulation of miR-29a, miR-21, and miR-122. The genetic and epigenetic changes in the pathogenesis and hepatocarcinogenesis potentially serve as potential diagnostic biomarkers and/or therapeutic targets.

Viral infection in community acquired pneumonia patients with fever: a prospective observational study.

BACKGROUND: Patients with community acquired pneumonia (CAP) caused by viruses can develop severe complications, which result in hospitalization and death. The purpose of this study was to analyse the aetiology, incidence, clinical characteristics, and outcomes of CAP patients with fever during non-pandemics, and then to provide theoretical basis for accurate diagnosis and treatment in CAP patients. METHODS: An enrolment system was established for monitoring the CAP patients with fever. Multiplex polymerase chain reaction (mPCR) kits were used to detect 10 viruses [influenza A and B, adenovirus (ADV), respiratory syncytial virus (RSV) A and B, picornavirus, parainfluenza virus (PIV), coronavirus, human metapneumovirus (HMPV), and bocavirus]. Data on age, gender, underlying diseases, complications, laboratory indexes, and outcomes were collected by physicians. RESULTS: This prospective study included 320 patients with fever. Among them, 23.4% were viral-positive by mPCR, with influenza virus most prominent followed by picornavirus. Strong variation in seasonal distribution was shown in viral infections, with peak months from December to February. Patients with influenza infection were likely to be taken to emergency rooms and have respiratory failure with higher creatinine kinase levels and lower white blood cell counts. Streptococcus pneumoniae followed by haemophilus influenzae were the most common bacteria in viral co-infections, which accounted for one third of virus-positive patients. Viral CAP and mixed CAP were not independent factors for death. In addition, lactate dehydrogenase (LDH) >246 IU/L [odds ratio (OR) =7.06, 95% confidence interval (CI): 2.15-23.2, P=0.001], and serum calcium <2.18 mmol/L (OR =6.67, 95% CI: 1.42-31.3, P=0.016) were associated with death. CONCLUSIONS: Viruses play an important role in CAP patients with fever, a systematic clinical, radiological and biological analysis of these patients can contribute to effective therapy that may prevent the development of CAP and improve the outcomes. The present work showed an elaborate analysis evidence of viral infection among fever CAP inpatients.

Investigating genetic-and-epigenetic networks, and the cellular mechanisms occurring in Epstein-Barr virus-infected human B lymphocytes via big data mining and genome-wide two-sided NGS data identification.

Epstein-Barr virus (EBV), also known as human herpesvirus 4, is prevalent in all human populations. EBV mainly infects human B lymphocytes and epithelial cells, and is therefore associated with their various malignancies. To unravel the cellular mechanisms during the infection, we constructed interspecies networks to investigate the molecular cross-talk mechanisms between human B cells and EBV at the first (0-24 hours) and second (8-72 hours) stages of EBV infection. We first constructed a candidate genome-wide interspecies genetic-and-epigenetic network (the candidate GIGEN) by big database mining. We then pruned false positives in the candidate GIGEN to obtain the real GIGENs at the first and second infection stages in the lytic phase by their corresponding next-generation sequencing data through dynamic interaction models, the system identification approach, and the system order detection method. The real GIGENs are very complex and comprise protein-protein interaction networks, gene/microRNA (miRNA)/long non-coding RNA regulation networks, and host-virus cross-talk networks. To understand the molecular cross-talk mechanisms underlying EBV infection, we extracted the core GIGENs including host-virus core networks and host-virus core pathways from the real GIGENs using the principal network projection method. According to the results, we found that the activities of epigenetics-associated human proteins or genes were initially inhibited by viral proteins and miRNAs, and human immune responses were then dysregulated by epigenetic modification. We suggested that EBV exploits viral proteins and miRNAs, such as EBNA1, BPLF1, BALF3, BVRF1 and miR-BART14, to develop its defensive mechanism to defeat multiple immune attacks by the human immune system, promotes virion production, and facilitates the transportation of viral particles by activating the human genes NRP1 and CLIC5. Ultimately, we propose a therapeutic intervention comprising thymoquinone, valpromide, and zebularine to act as inhibitors of EBV-associated malignancies.

Clinical characteristics and validation of bronchiectasis severity score systems for post-tuberculosis bronchiectasis.

INTRODUCTION: Lung damage related to tuberculosis is a major contributor to the etiology of bronchiectasis in China. It is unknown whether bronchiectasis severity score systems are applicable in these cases. OBJECTIVES: To evaluate the clinical characteristics and validation of bronchiectasis severity score systems for post-tuberculosis bronchiectasis. METHODS: The study enrolled 596 bronchiectasis patients in Shanghai Pulmonary Hospital between January 2011 and December 2012. The data for calculating FACED and bronchiectasis severity index (BSI) scores along with mortality, readmission, and exacerbation outcomes were collected and analyzed within a follow-up period with a median length of 48 months (interquartile range 43-54 months). RESULTS: The study enrolled 101 post-tuberculosis bronchiectasis patients and 495 non-tuberculosis bronchiectasis patients. Compared with non-post-tuberculosis bronchiectasis, post-tuberculosis bronchiectasis patients experienced less bilateral bronchiectasis (P = .004), a higher frequency of right upper lobe involvement (P < .001) and showed the cylindrical type more often (P < .001). Follow-up data indicated that both scoring systems were able to predict 48(43-54) month mortality in post-tuberculosis patients as assessed by the area under the receiver operator characteristic curve (AUC) (FACED AUC = 0.81, BSI AUC = 0.70), but they did not predict readmission (FACED and BSI = 0.56) or exacerbation (FACED and BSI = 0.52) well. CONCLUSIONS: There are apparent differences on radiologic features between bronchiectasis patients with and without history of pulmonary tuberculosis. Both FACED and BSI can predict mortality in post-tuberculosis bronchiectasis.

Changes of signal transductivity and robustness of gene regulatory network in the carcinogenesis of leukemic subtypes via microarray sample data.

Mutation accumulation and epigenetic alterations in genes are important for carcinogenesis. Because leukemogenesis-related signal pathways have been investigated and microarray sample data have been produced in acute myeloid leukemia (AML), myelodysplastic syndromes (MDS) and normal cells, systems analysis in coupling pathways becomes possible. Based on system modeling and identification, we could construct the coupling pathways and their associated gene regulatory networks using microarray sample data. By applying system theory to the estimated system model in coupling pathways, we can then obtain transductivity sensitivity, basal sensitivity and error sensitivity of each protein to identify the potential impact of genetic mutations, epigenetic alterations and the coupling of other pathways from the perspective of energy, respectively. By comparing the results in AML, MDS and normal cells, we investigated the potential critical genetic mutations and epigenetic alterations that activate or repress specific cellular functions to promote MDS or AML leukemogenesis. We suggested that epigenetic modification of ß-catenin and signal integration of CSLs, AP-2α, STATs, c-Jun and ß-catenin could contribute to cell proliferation at AML and MDS. Epigenetic regulation of ERK and genetic mutation of p53 could lead to the repressed apoptosis, cell cycle arrest and DNA repair in leukemic cells. Genetic mutation of JAK, epigenetic regulation of ERK, and signal integration of C/EBPα could result in the promotion of MDS cell differentiation. According to the results, we proposed three drugs, decitabine, genistein, and monorden for preventing AML leukemogenesis, while three drugs, decitabine, thalidomide, and geldanamycin, for preventing MDS leukemogenesis.

Pseudomonas aeruginosa isolation in patients with non-cystic fibrosis bronchiectasis: a retrospective study.

OBJECTIVES: Pseudomonas aeruginosa (P. aeruginosa) occupies an important niche in the pathogenic microbiome of bronchiectasis. The objective of this study is to evaluate the clinical characteristics and prognostic value of P. aeruginosa in Chinese adult patients with bronchiectasis. METHODS: This retrospective and follow-up study enrolled 1188 patients diagnosed with bronchiectasis at Shanghai Pulmonary Hospital between January 2011 and December 2012. The patients' clinical data including anthropometry, clinical symptoms, serum biomarkers, radiographic manifestations and lung function indices were reviewed. The median follow-up duration (IQR) was 44 (40-54) months, during which 289 patients were lost to follow-up. Data from 899 patients were collected and analysed for the outcomes of mortality, annual exacerbation frequency and health-related quality of life. RESULTS: P. aeruginosa was isolated from 232 patients, alongside other pathogens such as Aspergillus (n=75) and Candida albicans (n=72). There were 74 deaths (12% of patients with P. aeruginosa, 7.3% of those without) over the course of the follow-up. The isolation of P. aeruginosa was a risk factor for all-cause mortality (HR, 3.07; 95% CI 1.32 to 7.15) and was associated with high rates of exacerbations (ie, ≥3 exacerbations per year of follow-up) (HR, 2.40; 95% CI 1.20 to 4.79). Patients with P. aeruginosa also had worse scores on the Hospital Anxiety and Depression Scale (anxiety, p=0.005; depression, p<0.001), the Leicester Cough Questionnaire (p=0.033) and the modified Medical Research Council scale (p=0.001) compared with those without P. aeruginosa. CONCLUSIONS: Isolation of P. aeruginosa in patients with bronchiectasis is a significant prognostic indicator and should be a major factor in the clinical management of the disease.