Genome-scale approach to reconstructing the phylogenetic tree of psyllids (superfamily Psylloidea) with account of systematic bias.

Psyllids (class Insecta: order Hemiptera: superfamily Psylloidea) are a taxonomically and phylogenetically challenging clade. Recent studies have largely advanced the phylogeny of this group, yet the family-level relationships among Aphalaridae, Carsidaridae, and others remain unresolved. Genome-scale phylogenetic analysis is known to provide a finer resolution for problems like that. However, such phylogenomics also introduces new problems: incorrect trees with high confidence yielded due to systematic error (bias). Here we addressed these issues using hundreds of single-copy orthologous (SCO) genes in psyllid transcriptomes and genomes. Our analyses revealed conflicts between the nucleotide-based and amino-acid-based phylogenetic trees. While the nucleotide-based phylogeny strongly supported the (Aphalaridae + Carsidaridae) + Others relationship, the amino-acid-based one recovered Aphalaridae + (Carsidaridae + Others) with 100% support. Further inspection revealed significant compositional heterogeneity in nucleotide sequences for 67% of SCO genes, but not in the corresponding translated amino acid sequences. We then used different strategies to combat this compositional bias, and found that using the RY-coding strategy (coding the standard nucleotides as purines and pyrimidines) the nucleotide-based phylogeny became consistent with the amino-acid-based one. We further applied RY-coding to a published concatenated nucleotide dataset and recovered the Aphalaridae monophyly (which is refuted by the original literature on non-recoded sequences) at the base of psyllid tree. Moreover, it was found that variations in evolutionary rate could lead to errors in nucleotide-based phylogeny. The fast-evolving Heteropsylla cubana (Psyllidae: Ciriacreminae) was incorrectly placed within the subfamily Psyllinae. This bias can be avoided by using data removal or RY-coding strategies. Together, our results strongly support the family relationship of Aphalaridae + (Carsidaridae + Others), and show that the amino-acid-based concatenation analysis is more robust than nucleotide-based one. Future phylogenomic analysis of psyllid nucleotide sequences should take into account methods such as the RY-coding scheme to address potential systematic biases arising from composition and rate heterogeneities.

Higher-order matrix nonlinear Schrödinger equation with the negative coherent coupling: binary Darboux transformation, vector solitons, breathers and rogue waves.

Optical fiber communication plays a crucial role in modern communication. In this work, we focus on the higher-order matrix nonlinear Schrödinger equation with negative coherent coupling in a birefringent fiber. For the slowly varying envelopes of two interacting optical modes, we construct a binary Darboux transformation using the corresponding Lax pair. With vanishing seed solutions and the binary Darboux transformation, we investigate vector degenerate soliton and exponential soliton solutions. By utilizing these soliton solutions, we demonstrate three types of degenerate solitons and double-hump bright solitons. Furthermore, considering non-vanishing seed solutions and applying the binary Darboux transformation, we obtain vector breather solutions, and present the vector single-hump beak-type Akhmediev breather, Kuznetsov-Ma breathers, double-hump beak-type Akhmediev breather, Kuznetsov-Ma breathers, and vector degenerate beak-type breathers. Additionally, we take the limit in the breather solutions and derive vector rogue wave solutions. We illustrate the beak-type rogue waves and bright-dark rogue waves. Humps of these vector double-hump waves can separate into two individual humps. The results obtained in this work may potentially provide valuable insights for experimentally manipulating the separation of two-hump solitons, breathers, and rogue waves in optical fibers.

Bubble Management for Electrolytic Water Splitting by Surface Engineering: A Review.

During electrocatalytic water splitting, the management of bubbles possesses great importance to reduce the overpotential and improve the stability of the electrode. Bubble evolution is accomplished by nucleation, growth, and detachment. The expanding nucleation sites, decreasing bubble size, and timely detachment of bubbles from the electrode surface are key factors in bubble management. Recently, the surface engineering of electrodes has emerged as a promising strategy for bubble management in practical water splitting due to its reliability and efficiency. In this review, we start with a discussion of the bubble behavior on the electrodes during water splitting. Then we summarize recent progress in the management of bubbles from the perspective of surface physical (electrocatalytic surface morphology) and surface chemical (surface composition) considerations, focusing on the surface texture design, three-dimensional construction, wettability coating technology, and functional group modification. Finally, we present the principles of bubble management, followed by an insightful perspective and critical challenges for further development.

Inhibition of YAP Sensitizes the Selumetinib Treatment for Neurofibromatosis Type 1 Related Plexiform Neurofibroma.

Background: Targeted therapy of Neurofibromatosis type 1 (NF1) related plexiform neurofibroma (pNF) aiming at MEK molecule has not demonstrated a convincing result for complete disease inhibition, probably due to other signal pathways crosstalk. Our previous study revealed an increased nuclear translocation of YAP molecule in NF1 related pNF. Herein, we decided to further investigate the therapeutic relations of YAP interference during the MEK treatment against NF1 related pNF. Methods: By means of selumetinib (MEK-inhibitor), RNA-sequencing was firstly performed to identify the changes of signal pathways in pNF Schwann cells, which was probably related to YAP regulation. Nuclear-cytoplasmic fractionation and western blotting were performed to show the intracellular YAP changes under selumetinib treatment. Thirdly, a series of in vitro assays were performed including flow cytometry, CCK-8, and colony/sphere formation under dual treatment of selumetinib and verteporfin (YAP-inhibitor). In addition, Chou-Talalay method was adopted to evaluate the synergistic inhibiting effects of such drug combination. Xenograft study was also used to detect the combining effects in vivo. Results: RNA-sequencing revealed that selumetinib treatment might be associated with the undesirable activation of Hippo pathway in NF1 related pNF tumor cells, which might reduce its pharmaceutic effects. Next, nuclear-cytoplasmic fractionation and further studies demonstrated that selumetinib could promote the nuclear translocation and transcriptional activation of YAP in vitro, which might cause the aforementioned resistance to selumetinib treatment. Additionally, when combined treatments were performed based on verteporfin and selumetinib, synergistic effects were observed on cytotoxicity of NF1 related pNF tumor cells in vitro and in vivo xenograft models. Conclusion: YAP inhibition can effectively sensitize NF1 related pNF tumor cells to selumetinib. Dual targeting of YAP and MEK might be a promising therapeutic strategy for treating NF1 related pNF.

Diagnostic value of multiple b-value diffusion-weighted imaging in discriminating the malignant from benign breast lesions.

OBJECTIVE: The conventional breast Diffusion-weighted imaging (DWI) was subtly influenced by microcirculation owing to the insufficient selection of the b values. However, the multiparameter derived from multiple b-value exhibits more reliable image quality and maximize the diagnostic accuracy. We aim to evaluate the diagnostic performance of stand-alone parameter or in combination with multiparameter derived from multiple b-value DWI in differentiating malignant from benign breast lesions. METHODS: A total of forty-one patients diagnosed with benign breast tumor and thirty-eight patients with malignant breast tumor underwent DWI using thirteen b values and other MRI functional sequence at 3.0 T magnetic resonance. Data were accepted mono-exponential, bi-exponential, stretched-exponential, aquaporins (AQP) model analysis. A receiver operating characteristic curve (ROC) was used to evaluate the diagnostic performance of quantitative parameter or multiparametric combination. The Youden index, sensitivity and specificity were used to assess the optimal diagnostic model. T-test, logistic regression analysis, and Z-test were used. P value < 0.05 was considered statistically significant. RESULT: The ADCavg, ADCmax, f, and α value of the malignant group were lower than the benign group, while the ADCfast value was higher instead. The ADCmin, ADCslow, DDC and ADCAQP showed no statistical significance. The combination (ADCavg-ADCfast) yielded the largest area under curve (AUC = 0.807) with sensitivity (68.42%), specificity (87.8%) and highest Youden index, indicating that multiparametric combination (ADCavg-ADCfast) was validated to be a useful model in differentiating the benign from breast malignant lesion. CONCLUSION: The current study based on the multiple b-value diffusion model demonstrated quantitatively multiparametric combination (ADCavg-ADCfast) exhibited the optimal diagnostic efficacy to differentiate malignant from benign breast lesions, suggesting that multiparameter would be a promising non-invasiveness to diagnose breast lesions.

Clinical indocyanine green-based silk fibroin theranostic nanoprobes for in vivo NIR-I/II fluorescence imaging of cervical diseases.

Cervical diseases such as lymph node disease and tubal obstruction have threatened women's health. However, the traditional diagnostic methods still have shortcomings. NIR-II fluorescence imaging with advantages of low scattering, negligible autofluorescence, and high spatial resolution could be an ideal option. To obtain high quality NIR-II fluorescence imaging, selecting appropriate nanoprobes becomes the important issue. As a small molecular photothermal agent, extensive applications of ICG are rather limited because of its drawbacks. Herein, natural silk fibroin (SF) was synthesized and encapsulated ICG molecules to form SF@ICG nanoparticles (NPs). After detailed analysis, SF@ICG NPs showed excellent stability and long circulation time, as well as strong NIR-II fluorescence emission, well photo-stability, biocompatibility and well photothermal property under 808 nm laser irradiation. Furthermore, SF@ICG NPs were utilized for NIR-II fluorescence imaging of lymph node/lymphangiography and angiography of fallopian tubes. The process of fallopian tubes could be detected with high resolution and high sensitivity.

The Value of Contrast-Enhanced Ultrasound in the Detection of Sentinel Lymph Nodes in Malignant Melanoma.

OBJECTIVE: To evaluate the location and characterization value of contrast-enhanced ultrasound (CEUS) in the detection of sentinel lymph nodes (SLNs) in malignant melanoma. METHODS: SLNs and the lymph node network were tracked by subcutaneous injection of ultrasonic contrast agent around the tumor and preoperative localization, and qualitative analyses were performed. The SLNs were also detected by the intraoperative subcutaneous injection of carbon nanoparticles, and the findings were compared with lymph nodes located by CEUS. The accuracy of the preoperative lymph node identification was evaluated by the results of postoperative pathology, which served as the gold standard of detection. RESULTS: In 47 patients with malignant melanoma, the mean number of SLNs detected by CEUS was 1.72 ± 0.10, while that by carbon nanoparticle administration it was 1.79 ± 1.07 (P = .371 > .05). Seven cases of lymph node metastasis were detected by CEUS, with a sensitivity of 70.0%, specificity of 97.3%, positive predictive value of 87.5%, negative predictive value of 92.3%, and accuracy of 91.5%. There was high consistency between the findings of CEUS and pathology in differentiating benign and malignant lymph nodes (kappa = 0.726, χ2  = 25.243, P < .001). CONCLUSIONS: CEUS can localize and differentiate SLNs in malignant melanoma, and thus, may potentially guide clinical treatment in the future.

[Diagnosis and treatment of incomplete Kawasaki disease in children]. / å„¿ç«¥ä¸å®Œå ¨æ€§å·å´Žç— çš„è¯Šæ²».

Kawasaki disease (KD) is a febrile disease mainly observed in children aged <5 years, with medium- and small-vessel vasculitis as the main lesion. Although KD has been reported for more than 50 years and great progress has been made in the etiology and pathology of KD in recent years, there is still a lack of specific indicators for the early diagnosis of KD, especially with more difficulties in the diagnosis of incomplete Kawasaki disease (IKD). At present, there are no clear diagnostic criteria for IKD, which leads to the failure of the timely identification and standardized treatment of IKD in clinical practice and even induce the development of coronary artery lesion. This article reviews the concept, epidemiological features, diagnosis, treatment, and follow-up management of IKD, in order to deepen the understanding of IKD among clinical workers and help to improve the clinical diagnosis and treatment of KD in China.

Response of net reduction rate in vegetation carbon uptake to climate change across a unique gradient zone on the Tibetan Plateau.

The Tibetan Plateau (TP) has a variety of vegetation types that range from alpine tundra to tropic evergreen forest, which play an important role in the global carbon (C) cycle and is extremely vulnerable to climate change. The vegetation C uptake is crucial to the ecosystem C sequestration. Moreover, net reduction in vegetation C uptake (NRVCU) will strongly affect the C balance of terrestrial ecosystem. Until now, there is limited knowledge on the recovery process of vegetation net C uptake and the spatial-temporal patterns of NRVCU after the disturbance that caused by climate change and human activities. Here, we used the MODIS-derived net primary production to characterize the spatial-temporal patterns of NRVCU. We further explored the influence factors of the net reduction rate in vegetation C uptake (NRRVCU) and recovery processes of vegetation net C uptake across a unique gradient zone on the TP. Results showed that the total net reduction amount of vegetation C uptake gradually decreased from 2000 to 2015 on the TP (Slope = -0.002, P < 0.05). Specifically, an increasing gradient zone of multi-year average of net reduction rate in vegetation carbon uptake (MYANRRVCU) from east to west was observed. In addition, we found that the recovery of vegetation net C uptake after the disturbance caused by climate change and anthropogenic disturbance in the gradient zone were primarily dominated by precipitation and temperature. The findings revealed that the effects of climate change on MYANRRVCU and vegetation net C uptake recovery differed significantly across geographical space and vegetation types. Our results highlight that the biogeographic characteristics of the TP should be considered for combating future climate change.

[Association of liver damage with coronary artery lesion and no response to intravenous immunoglobulin in the acute stage of Kawasaki disease]. / å·å´Žç— æ€¥æ€§æœŸè‚æŸå®³ä¸Žå† çŠ¶åŠ¨è„‰æŸä¼¤å’Œå ç–«çƒè›‹ç™½æ— ååº”çš„å ³ç³».

OBJECTIVES: To summarize the clinical features of liver damage in children in the acute stage of Kawasaki disease (KD), and to investigate the clinical value of liver damage in predicting coronary artery lesion and no response to intravenous immunoglobulin (IVIG) in children with KD. METHODS: The medical data were collected from 925 children who were diagnosed with KD for the first time in Beijing Children's Hospital from January 1, 2016 to December 31, 2017. According to the presence or absence of abnormal alanine aminotransferase (ALT) level on admission, the children were divided into a liver damage group (n=284) and a non-liver damage group (n=641). A logistic regression analysis was used to investigate the clinical value of the indicators including liver damage in predicting coronary artery lesion and no response to IVIG in children with KD. RESULTS: Compared with the non-liver damage group, the liver damage group had a significantly earlier admission time and significantly higher serum levels of inflammatory indicators (P<0.05). The liver damage group had a significantly higher incidence rate of coronary artery lesion on admission than the non-liver damage group (P=0.034). After initial IVIG therapy, the liver damage group had a significantly higher proportion of children with no response to IVIG than the non-liver damage group (P<0.001). In children with KD, coronary artery lesion was associated with the reduction in the hemoglobin level and the increases in platelet count, C-reactive protein, and ALT (P<0.05), and no response to IVIG was associated with limb changes, the reduction in the hemoglobin level, the increases in platelet count, C-reactive protein, and ALT, and coronary artery lesion (P<0.05). CONCLUSIONS: Compared with those without liver damage, the children in the early stage of KD with liver damage tend to develop clinical symptoms early and have higher levels of inflammatory indicators, and they are more likely to have coronary artery lesion and show no response to IVIG treatment.

Dopamine receptor D2 on CD4+ T cells is protective against neuroinflammation and neurodegeneration in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is a chronic neurodegenerative disease. Recently, neuroinflammation driven by CD4+ T cells has been involved in PD pathophysiology. Human and murine lymphocytes express all the five subtypes of dopamine receptors (DRs), DRD1 to DRD5. However, roles of DRs particularly DRD2 expressed on CD4+ T cells in PD remain elucidated. Global Drd1- or Drd2-knockout (Drd1-/- or Drd2-/-) mice or CD4+ T cell-specific Drd2-knockout (Drd2fl/fl/CD4Cre) mice were intraperitoneally injected with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to induce PD with the different mutants. On the 7th day following MPTP injection, mice were assessed for dopaminergic neurodegeneration, locomotor impairments, microglial activation, as well as CD4+ T-cell differentiation and function. Furthermore, in vitro CD4+ T cells were exposed to DRD2 agonist and antagonist and then differentiation and function of the cells were determined. MPTP induced dopaminergic neuronal loss in the nigrostriatal system, motor coordinative and behavioral impairments, microglial activation, and CD4+ T-cell polarization to pro-inflammatory T-helper (Th)1 and Th17 phenotypes. Importantly, either Drd2-/- or Drd2fl/fl/CD4Cre mice manifested more severe dopaminergic neurodegeneration, motor deficits, microglial activation, and CD4+ T-cell bias towards Th1 and Th17 phenotypes in response to MPTP, but Drd1-/- did not further alter MPTP intoxication. DRD2 agonist sumanirole inhibited shift of CD4+ T cells obtained from MPTP-intoxicated mice to Th1 and Th17 phenotypes and DRD2 antagonist L-741,626 reversed sumanirole effects. These findings suggest that DRD2 expressed on CD4+ T cells is protective against neuroinflammation and neurodegeneration in PD. Thus, developing a therapeutic strategy of stimulating DRD2 may be promising for mitigation of PD.

Increased nuclear translation of YAP might act as a potential therapeutic target for NF1-related plexiform neurofibroma.

Plexiform neurofibroma (pNF) in the head and neck is a characteristic feature in patients with neurofibromatosis type 1 (NF1) and is associated with significant disfigurement and psychological distress. Yes-associated protein (YAP), the key molecule involved in the Hippo pathway, is a vital transductor that regulates the proliferation and remyelinating of Schwann cells. The functional status of YAP and its feasibility as a potential target are still unknown in pNF. A total of 17 pNF tumor tissue specimens from the head and neck were collected at the Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. Histologically, diagnosis of the Schwann cell region in pNF was achieved with hematoxylin-eosin staining, positive reactions for S100, SOX10, ERK and p-ERK, and low identification of Ki67 and SMA. Compared with normal nerve tissue, obviously increased nuclear YAP was detected in the Schwann cell region of pNF, with a mean nuclear staining rate of 67.11%. Based on the shNF1 Schwann cell model (the RSC96 cell line), with upregulated expression of RAS, ERK and p-ERK, p-YAP (Ser127) and p-YAP (Ser397) were significantly decreased and total YAP and nuclear YAP were increased. According to a confocal assay, the interference of shNF1 substantially promoted YAP nuclear translocation. Compared with control Schwann cells, the YAP inhibitor CA3 might have a more sensitive effect (IC50: NC=0.96±0.04, shNF1=0.71±0.02, P<0.05) on the shNF1 Schwann cell model than the classic MEK1/2 inhibitor selumetinib (IC50: NC=14.36±0.95, shNF1=24.83±0.98, P>0.05). For in vivo inhibition, the CA3 group and the selumetinib group displayed a similar inhibition effect with no significant difference. Increased nuclear translation and the functional state of YAP implies that the YAP-Hippo pathway might play an important role in the formation and remyelination of pNF. Compared with selumetinib, the YAP inhibitor can exhibit a similar but more sensitive effect on NF1-/- Schwann cells. These observations imply that YAP as a novel or adjuvant therapy target in the treatment of pNF.

A Novel Laryngoscope-assisted Method for Sealing Pharyngocutaneous Fistula.

ABSTRACT: Pharyngocutaneous fistula (PCF) is one of the most common but stranded complications for salvage laryngectomy. As for localized fistula, there is no convincing standard and method to cure. This paper described a patient who was submitted to extensive resection of mass in right lingual root, total laryngectomy, and pharyngoesophageal reconstruction with an anterolateral thigh flap (ALTF), because of recurred carcinoma of right lingual root which invaded bilateral epiglottis. 2 weeks after surgery, subsequent pharyngocutaneous fistula developed at the junction of the tracheostomy, and maintained over 2 months under conservative treatment. With the assistance of laryngoscope, inner and outer orificiums of fistula were found and sealed by bundled iodoform strip. 9 days after sealing, fistula had been already filled with fresh granulation tissue. During 2 years after surgery, the fistula area dose not recur. This technique provides a safe and effective way for sealing the inner and outer orificiums of fistula.

Evaluation of a beneficial effect of adjuvant chemotherapy in patients with stage I triple-negative breast cancer: a population-based study using the SEER 18 database.

PURPOSE: To evaluate the effect of adjuvant chemotherapy on improving the prognosis of patients with stage I triple-negative breast cancer (TNBC). METHODS: TNBC patients diagnosed in the SEER 18 database from 2010 to 2015 were included. Kaplan-Meier plots and log-rank tests were used to compare the differences in breast cancer-specific survival (BCSS) and overall survival (OS) between subgroups of variables. A Cox proportional hazard model was used to determine the prognostic factors affecting BCSS and OS. RESULTS: A total of 9256 patients were enrolled in this study. Among these patients, 380 died from breast cancer, and 703 died from all causes. Patients who received chemotherapy had significantly better BCSS and OS than those who did not receive chemotherapy for stage T1cN0M0 (BCSS, hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.51-0.90; OS, HR = 0.54, 95% CI 0.44-0.67) and stage IB (BCSS, HR = 0.39, 95% CI 0.16-0.95; OS, HR = 0.41, 95% CI 0.19-0.87) disease. Patients who received chemotherapy did not have significantly better BCSS or OS than those who did not receive chemotherapy for stage T1aN0M0 or T1bN0M0 disease. The patients who received chemotherapy in the poorly differentiated and undifferentiated groups had better BCSS (HR = 0.68, 95% CI 0.52-0.88) and OS (HR = 0.54, 95% CI 0.44-0.66) than the patients who did not receive chemotherapy. CONCLUSION: According to current clinical guidelines, patients with stage T1bN0M0 TNBC are probably overtreated. The prognosis of these patients with stage T1aN0M0 or T1bN0M0 disease is good enough that adjuvant chemotherapy cannot improve it further.

Septic pulmonary embolism in China: clinical features and analysis of prognostic factors for mortality in 98 cases.

BACKGROUND: To investigate the clinical features of septic pulmonary embolism (SPE) cases and prognostic factors for in-hospital mortality in China. METHODS: A retrospective analysis was conducted of SPE patients hospitalized between January 2007 and June 2018 in the Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University. RESULTS: A total of 98 patients with SPE were identified. All patients had bilateral multiple peripheral nodules on chest computed tomography. The most common pathogen found in blood culture was Staphylococcus aureus (10/33, 30.3%). Transthoracic echocardiography was performed in 39 patients and 20 showed vegetations. Bronchoscopy was performed in 24 patients. Bronchoalveolar lavage fluid (BALF) was obtained from 15 patients (62.5%) and showed predominantly polymorphonuclear cell infiltration (52%, range of 48%~ 63%). Four patients received transbronchial lung biopsy, and histopathological examinations revealed suppurative pneumonia and organizing pneumonia. The in-hospital mortality rate was 19.4%. Age (odds ratio [OR] 1.100; 95% confidence interval [CI] 1.035-1.169), hypotension (OR 7.260; 95% CI 1.126-46.804) and ineffective or delay of empirical antimicrobial therapy (OR 7.341; 95% CI 1.145-47.045) were found to be independent risk factors for in-hospital mortality, whereas drainage treatment was found to be a protective factor (OR 0.33; 95% CI 0.002-0.677). CONCLUSIONS: SPE cases presented with nonspecific clinical manifestations and radiologic features. Blood cultures and bronchoscopy are important measures for early diagnosis and differential diagnosis. There is relationship between primary infection sites and the type of pathogen. Maintaining normal blood pressure and providing timely and appropriate initial antimicrobial therapy for effective control of the infection could improve prognosis.

Transgenic Expression of A Venous Malformation Related Mutation, TIE2-R849W, Significantly Induces Multiple Malformations of Zebrafish.

A TIE2 mutation causing arginine-to-tryptophan substitution at residue 849 (TIE2-R849W) is commonly identified in heredofamilial venous malformation. However, there is no in vivo model to confirm the pathogenic role of TIE2-R849W. Humanized TIE2-R849W plasmid was constructed via PCR-mediated site-directed mutagenesis. After transcription and micro-injection, TIE2-R849W significantly induces multiple malformations in zebrafish: caudal vein plexus (CVP) defect, eye abnormalities, forebrain formation perturbations, and mandibular malformation. Histologically, these phenotypes accompany aphakia, confused retina plexiform layer, abnormal mandibular cartilage, ectopic myelencephalon proliferation and aberrant location of neurogliocytes. According to qRT-PCR, except for high expression of egfl7, the other CVP-related genes cd146, nr2f1a, and s1pr1 are not significantly different from control. TIE2-R849W also induced upregulation of the wnt signaling pathway. Gene array in vitro shows that under the effect of TIE2-R849W, consistent with high expression of pik3 and foxo1, high levels of egfl7, wnt9a, lrp5 and dkk1 were partly confirmed. This in vivo model directly identifies the venous-related pathogenic role of TIE2-R849W. Under up-regulation of TIE2-R849W, egfl7 could be considered a potential reason for venous defects. Moreover, the wnt pathway may perform an important role as a key trigger for head multi-malformations.

Gut Microbiota Disruption in Septic Shock Patients: A Pilot Study.

BACKGROUND The composition of the intestinal microbiota and its effect on septic shock patients in the intensive care unit (ICU) is unknown. In the present study we explored the hypothesis that bacterial diversity is decreased in septic shock patients and that this diversity may be improved by use of probiotics or enteral nutrition. MATERIAL AND METHODS A total of 15 stool samples were collected prospectively from septic shock patients in the ICU, while 15 samples from healthy subjects served as controls. Bacterial DNA was submitted for 16S rDNA gene sequencing. The relationship between intestinal microbiota and prognosis was evaluated. RESULTS Significantly lower bacterial diversity was found in septic shock patients compared with healthy subjects (p<0.05). However, there was no difference in bacterial diversity in the presence or absence of probiotics (p=0.59), enteral nutrition (p=0.59), or in-hospital death (p=0.93) in septic shock patients. A high abundance of Proteobacteria and Fusobacteria was observed in most septic shock patients, whereas low abundance was observed in healthy subjects (mean relative proportion: 23.71% vs. 3.53%, p<0.05; 1.27% vs. 0.12%, p=0.59). CONCLUSIONS Bacterial diversity was decreased, and 1 or 2 rare bacterial species were overgrown in septic shock patients. Bacterial diversity was not improved by use of probiotics or enteral nutrition. The small sample size of our study limits the interpretation of results.

[Improvement and application of a fast labeling system for bulk internalized vesicles].

To study trafficking of bulk internalized vesicles such as macropinosome and lysosome in live cells, an efficient and convenient assay was established according to the axon turning assay. By injecting indicator or fluorescent dyes through a micropipette with air pressure into cell cultures to create a stable gradient around the micropipette tip, vesicles were indicated and labeled. With live cell imaging, the whole process was recorded. Without wash-out of fluorescent dyes and transferring, this assay is an effective, fast labeling system for bulk internalized vesicles, and can also be combined with imaging system.

Screening and identification of potential hypoglycemic components in Zeng Ye Tang by high-performance liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry.

Zeng Ye Tang, a famous prescription consisting of Xuanshen, Maidong, and Shengdi (5:4:4), has been used in China for a long time to treat diabetes caused by excessive heat with yin deficiency. Although many studies have investigated the pharmacological effects of Zeng Ye Tang, the compounds responsible for its hypoglycemic effect have not been identified. In this study, 50 compounds in Zeng Ye Tang were identified by high-performance liquid chromatography coupled with tandem quadrupole time-of-flight mass spectrometry. From these 50 compounds, nine cell-interacted compounds were identified by biospecific cell extraction using 3T3-L1 adipocytes. Moreover, nine potential active compounds that could be released into the blood were also acquired through serum pharmacochemical analysis in normal and diabetic rats after administration with Zeng Ye Tang. According to the established quantitative analytical method of nine constituents by high-performance liquid chromatography, six shared prototype constituents (catalpol/harpagide/p-coumaric acid/harpagoside/angoroside C/cinnamic acid (75.56:19.74:1.00:15.11:20.36:7.65), were screened and verified to exert remarkable hypoglycemic activity on type 2 diabetic mice. In conclusion, the six shared constituents may be responsible for the hypoglycemic activity of Zeng Ye Tang.

miR-200 and miR-96 families repress neural induction from human embryonic stem cells.

The role of miRNAs in neuroectoderm specification is largely unknown. We screened miRNA profiles that are differentially changed when human embryonic stem cells (hESCs) were differentiated to neuroectodermal precursors (NEP), but not to epidermal (EPI) cells and found that two miRNA families, miR-200 and miR-96, were uniquely downregulated in the NEP cells. We confirmed zinc-finger E-box-binding homeobox (ZEB) transcription factors as a target of the miR-200 family members and identified paired box 6 (PAX6) transcription factor as the new target of miR-96 family members via gain- and loss-of-function analyses. Given the essential roles of ZEBs and PAX6 in neural induction, we propose a model by which miR-200 and miR-96 families coordinate to regulate neural induction.