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Objective In the present study, we evaluated the feasibility of a self-expanding venous stent for treating iliofemoral venous obstruction. Methods The present retrospective study reviewed the data from 49 patients who had undergone Zilver Vena (Cook Medical, Bloomington, Ind) stent placement for treatment of iliofemoral venous obstruction from September 2017 to March 2019. All patients had undergone received follow-up duplex ultrasound examinations to assess for stent patency. The Villalta scores and Venous Clinical Severity Scores (VCSSs) were also calculated to stratify the postoperative improvement in disease. Results Of the 49 patients, 19 had had acute deep vein thrombosis, 7, nonthrombotic iliac venous lesions, and 23, post-thrombotic syndrome. At 1 year after Zilver Vena stent placement, the primary, assisted primary, and secondary patency rates were 93.8%, 95.9%, and 97.9%, respectively. The baseline median Villalta score before treatment for those with post-thrombotic syndrome was 19 (range, 11-30), and the median VCSS for the patients with post-thrombotic syndrome and nonthrombotic iliac venous lesions was 11 (range, 6-25). At 1 year after stent placement, the median Villalta score for the post-thrombotic syndrome patients was 4.0 (range, 2-18), and the median VCSS for the post-thrombotic syndrome and nonthrombotic iliac venous lesions patients was 3.0 (range, 2-12). Conclusions Venous placement of self-expanding stents offers excellent 1-year patency rates and improved the outcomes of patients with iliofemoral venous obstruction caused by acute deep vein thrombosis, nonthrombotic iliac venous lesions, and post-thrombotic syndrome.

Homocysteine (Hcy) is considered as a modifiable risk factor for vascular disease. This study was aimed to explore the association between serum concentration and the severity of primary chronic venous disease (CVD).Clinical data of 582 patients diagnosed with primary CVD were collected and analyzed retrospectively. The Clinical Etiology Anatomy Pathophysiology classification system was used to grade the severity of chronic venous disease. Patients were divided into 2 groups (group A: C1-C3; group B: C4-C6). The association between serum homocysteine levels and the severity of primary chronic venous disease was investigated using rank sum test and logistic regression.The difference between the level of homocysteine in each grade has statistical significance. Group A has higher median Hcy concentrations than Group B (15.40 μmol/L vs. 14.05 μmol/L, P0.01). Further binary logistic regression showed no statistical significance among the level of Hcy (11.00-14.75 μmol/L [OR 0.66, 95% CI 0.40-1.11, P= 0.12], 14.75-20.38μmol/L [OR 0.97, 95% CI 0.59-1.69, P = 0.89], ≥20.38 μmol/L [OR 0.67, 95% CI 0.41-1.10, P = 0.11]), but age (OR 1.03, 95% CI 1.01-1.04, P0.01) and female (OR 0.41, 95% CI 0.28-0.59, P0.01) are associated with more severe stages of CVD.Higher level of Hcy is associated with more severe stages of CVD, but it not an independent risk factor. However, Advanced age and female are risk factors for CVD development based on logistic regression analysis.

Objective:The aim of this study was to present the clinical characteristics and dynamic changes in laboratory parameters of the coronavirus disease 2019 (COVID-19) in Guangzhou, and explore the probable early warning indicators of disease progression.Method:We enrolled all the patients diagnosed with COVID-19 in the Guangzhou No. 8 People’s Hospital. The patients’ demographic and epidemiologic data were collected, including chief complaints, lab results, and imaging examination findings.Results:The characteristics of the patients in Guangzhou are different from those in Wuhan. The patients were younger in age, predominately female, and their condition was not commonly combined with other diseases. A total of 75% of patients suffered fever on admission, followed by cough occurring in 62% patients. Comparing the mild/normal and severe/critical patients, being male, of older age, combined with hypertension, abnormal blood routine test results, raised creatine kinase, glutamic oxaloacetic transaminase, lactate dehydrogenase, C-reactive protein, procalcitonin, D-dimer, fibrinogen, activated partial thromboplastin time, and positive proteinuria were early warning indicators of severe disease.Conclusion:The patients outside epidemic areas showed different characteristics from those in Wuhan. The abnormal laboratory parameters were markedly changed 4 weeks after admission, and also were different between the mild and severe patients. More evidence is needed to confirm highly specific and sensitive potential early warning indicators of severe disease.

High-throughput sequencing and Degradome sequencing revealed that miRNAs play crucial roles during the juvenile-to-mature stages in Chinese fir. In woody plants, the vascular cambium is a continuous cylinder of meristematic cells in the stem that produces secondary xylem (wood) and secondary phloem via cell division, expansion, secondary wall formation, lignification, and programmed cell death. MicroRNAs (miRNAs) are endogenous single-stranded non-coding RNAs that play important roles in plant growth and development. However, little is known about the roles of miRNAs in age-related changes in the vascular cambium, especially in conifers. Here, we compared age-related miRNAs in the vascular cambium of 3-(juvenile), 13-(transition), and 35-year-old (mature) Chinese fir (Cunninghamia lanceolata) trees. Transmission electron microscopy revealed changes in the morphology and cell wall thickness of the vascular cambium during the juvenile-to-mature phase transition. In addition, high-throughput sequencing and subsequent analyses identified 700 miRNAs, including 651 known and 49 novel miRNAs. We identified 105, 120, and 94 differentially expressed miRNAs at the three stages of growth. These miRNAs included various differentially expressed development-related and phytohormone-related miRNAs involved in cambium activity, cell division, and cell wall modification. Degradome sequencing revealed 38 target genes that were cleaved by 88 known miRNAs and 16 target genes that were cleaved by seven novel miRNAs. Additionally, miR159, miR164, and miR166 were highly expressed in the 13-transition stage; these miRNAs are involved in the auxin-signaling pathway. Moreover, miR156 levels were abundant in VC13 along with miR172 levels decreased during the juvenile-to-mature stages. These results provide insight into the roles of age-specific miRNAs in the growth of C. lanceolata and shed light on vascular cambium development in conifers.

In multicellular and even single-celled organisms, individual components are interconnected at multiscale levels to produce enormously complex biological networks that help these systems maintain homeostasis for development and environmental adaptation. Systems biology studies initially adopted network analysis to explore how relationships between individual components give rise to complex biological processes. Network analysis has been applied to dissect the complex connectivity of mammalian brains across different scales in time and space in The Human Brain Project. In plant science, network analysis has similarly been applied to study the connectivity of plant components at the molecular, subcellular, cellular, organic, and organism levels. Analysis of these multiscale networks contributes to our understanding of how genotype determines phenotype. In this review, we summarized the theoretical framework of plant multiscale networks and introduced studies investigating plant networks by various experimental and computational modalities. We next discussed the currently available analytic methodologies and multi-level imaging techniques used to map multiscale networks in plants. Finally, we highlighted some of the technical challenges and key questions remaining to be addressed in this emerging field.

Progranulin (PGRN) is a secreted glycoprotein with multiple biological functions in early embryogenesis, anti-inflammation, and neurodegeneration. A good model for the functional study of PGRN is the zebrafish with knockdown or knockout of grn, the gene encoding PGRN. Morpholino oligonucleotides (MOs) and zinc finger nucleases have been used to generate zebrafish grn models, yet they have shown inconsistent phenotypes due to either the neurotoxicity of the MOs or possible genetic compensation responses during gene editing. In this study, we generated stable grna (one of the major grn homologues of zebrafish) knockout zebrafish by using CRISPR/Cas9-mediated genome editing. A grna sgRNA was designed to target the similar repeated sequence shared by exon 13, exon 15, and exon 19 in zebrafish. The F1 generation with the frameshift mutation of + 4 bp (the addition of 4 bp to exon15), which causes a premature termination, was obtained and subjected to morphological and behavioral evaluation. The grna knockout zebrafish showed neurodevelopmental defects, including spinal motor neurons with shorter axons, decreased sensory hair cells, thinning of the outer nuclear layer and thickening of the inner nuclear layer of the retina, decreased expression of rhodopsin in the cone cells, and motor behavior changes. Moreover, the phenotypes of grna knockout zebrafish could be rescued with the Tol2 system carrying the grna gene. The grna knockout zebrafish model generated in this study provides a useful tool to study PGRN function and has potential for high-throughput drug screening for disease therapy.

KNSTRN is a component of the mitotic spindle, which was rarely investigated in tumorigenesis. AKT plays an essential role in tumorigenesis by modulating the phosphorylation of various substrates. The activation of AKT is regulated by PTEN and PIP3. Here, we prove KNSTRN is positively correlated with malignancy of bladder cancer and KNSTRN activates AKT phosphorylation at Thr308 and Ser473. More importantly, our study reveals that both KNSTRN and PTEN interact with PH domain of AKT at cell membrane. The amount of KNSTRN interacted with AKT is negatively related to PTEN. Furthermore, PIP3 pull-down assay proves that KNSTRN promoted AKT movement to PIP3. These data suggest KNSTRN may activate AKT phosphorylation by promoting AKT movement to PIP3 and alleviating PTEN suppression. Based on the activation of AKT phosphorylation, our study demonstrates that KNSTRN promotes bladder cancer metastasis and gemcitabine resistance in vitro and in vivo. Meanwhile, the effect of KNSTRN on tumorigenesis and gemcitabine resistance could be restored by AKT specific inhibitor MK2206 or AKT overexpression. In conclusion, we identify an oncogene KNSTRN that promotes tumorigenesis and gemcitabine resistance by activating AKT phosphorylation and may serve as a therapeutic target in bladder cancer.

Galectin-3 (Gal-3), a member of the β-galactoside-binding lectin family, involved in tumor angiogenesis and metastasis, is considered a diagnostic biomarker and a promising treatment target for early cancer. Gal-3 recognizes the poly-N-acetyllactosamine (poly-LacNAc)-based carbohydrate motifs of glycoproteins and glycolipids. To date, protein glycosylation with poly-LacNAc has been mainly achieved by chemical or chemoenzymatic strategies. In this study, a green artificial biosynthesis pathway for catalyzing the poly-LacNAc glycosylation of protein was designed and developed in the cytoplasm of Escherichia coli. The pathway enlists a cytoplasmic sequential O-glycosylation polypeptide-glycosyltransferase from Streptococcus parasanguinis to establish a site-specific primer N-acetylglucosamine on the target protein, and two glycosyltransferases from Neisseria meningitidis and Helicobacter pylori to extend the poly-LacNAc chain. Rewiring the metabolic network of the strain, by applying a carbon absorption enforced intersection and orthogonal utilization system, achieved the goal of poly-LacNAc glycoprotein biosynthesis in the cytoplasm. This approach coupled phosphoenolpyruvate (PEP) generation from the second carbon source, glycerol, with PEP consumption by the PEP-dependent phosphotransferase system, to facilitate noncatabolic utilization of glucose. The content of LacNAc-linked and poly-LacNAc-linked glycoprotein purified from the engineered strain reached 17 mg L−1, ∼10 times that purified from the starting strain. Furthermore, the degree of polymerization of the poly-LacNAc glycoprotein was further improved by optimizing the pathway flux toward the availability of the two key nucleotide sugars. The purified glycoprotein carrying the LacNAc epitope displayed a high affinity for Gal-3. Finally, the concentration of poly-LacNAc glycoprotein reached 45.7 mg L−1 through optimizing various culture conditions. The cytoplasmic glycoengineering strategies used in this study open up new avenues for the efficient and green manufacturing of various glycoprotein structures with diverse biomedical applications, thus reducing or eliminating the use or generation of hazardous substances.

This study sought to validate the performance of simultaneous non-contrast angiography and intraplaque hemorrhage (SNAP) imaging in characterizing carotid IPH by histology. Thirty-five patients with carotid atherosclerotic disease (symptomatic 50–70% stenosis or > 70% stenosis) scheduled for carotid endarterectomy underwent 3.0-T carotid MR imaging by acquiring SNAP and magnetization-prepared rapid acquisition gradient-echo (MP-RAGE) sequences. Presence and area of IPH were separately evaluated on SNAP and MP-RAGE images. Presence and area of IPH were also assessed on histology. Agreement between SNAP/MP-RAGE and histology was determined in identify and quantify IPH using Cohen kappa, Spearman correlation, and Bland-Altman analyses. Of all 35 patients (mean age: 63.1 ± 8.8 years; 27 males), 128 slices with successful registration were eligible for analysis. The accuracy, sensitivity, specificity, and positive and negative predictive values were 86.7%, 85%, 89.6%, 93.2%, and 78.2% for SNAP, and 76.6%, 75%, 79.2%, 85.7%, and 65.5% for MP-RAGE in identification of IPH, respectively. In identification of IPH, the kappa value between SNAP and histology and between MP-RAGE and histology was 0.725 and 0.520, respectively. The correlation between SNAP and histology (r = 0.805, p < 0.001) was stronger than that between MP-RAGE and histology (r = 0.637, p < 0.001) in measuring IPH area. Bland-Altman analysis showed that, in measuring IPH area, the bias of SNAP (1.4 mm2, 95% CI: − 0.016 to 2.883) was smaller than that of MP-RAGE (1.7 mm2, 95% CI: − 0.039 to 3.430) compared with histology. This validation study by histology demonstrates that SNAP sequence better identifies and quantifies carotid intraplaque hemorrhage compared with traditional MP-RAGE sequence. • SNAP imaging showed better agreement with histology compared with MP-RAGE imaging, especially for the IPHs with small size. • SNAP sequence is a more effective tool to identify and quantify carotid IPH than traditional sequence of MP-RAGE that can help clinicians to optimizing the treatment strategy. • The plaque components of rich lipid pools or loose matrix and chronic/old IPH (cholesterol crystals) can lead to false positive and false negative results in SNAP and MP-RAGE imaging for identifying IPH.

Summary Almost all plants form trichomes, which protect them against insect herbivores by forming a physical barrier and releasing chemical repellents. Glandular trichomes produce a variety of specialized defensive metabolites, including volatile terpenes. Previous studies have shown that the defence hormone jasmonic acid (JA) affects trichome development and induces terpene synthases (TPSs) but the underlying molecular mechanisms remain unclear. Here, we characterized a loss‐of‐function allele of the HD‐ZIP IV transcription factor woolly (wo) and analysed its role in mediating JA signalling in tomato. We showed that knockout of wo led to extensive trichome defects, including structural and functional changes in type VI glandular trichomes, and a dramatic reduction in terpene levels. We further found that wo directly binds to TPS gene promoters to recruit SlMYC1, a JA signalling modulator, and that together these transcription factors promote terpene biosynthesis in tomato trichomes. The wo/SlMYC1 regulatory module is inhibited by SlJAZ2 through a competitive binding mechanism, resulting in a fine‐tuned JA response in tomato trichomes. Enhanced expression of SlMYC1 substantially increased terpene levels and improved tomato resistance to spider mites. Interestingly, we also found that SlMYC1 plays an additional role in glandular cell division and expansion in type VI trichomes, independent of JA. Together, our results reveal a novel, JA‐mediated regulatory mechanism that promotes insect resistance in tomato.

Secondary growth is a key characteristic of trees, which requires the coordination of multiple regulatory mechanisms including transcriptional regulators and microRNAs (miRNAs). However, the roles of microRNAs in the regulation of secondary growth need to be explored in depth. Here, the role of miR319a and its target, PtoTCP20, in the secondary growth of Populus tomentosa stem was investigated using genetic and molecular analyses. The expression level of miR319a gradually decreased from primary to secondary growth in P. tomentosa, while that of PtoTCP20 gradually increased. MiR319a overexpression in seedlings resulted in delayed secondary growth and decreased xylem production, while miR319a knockdown and PtoTCP20 overexpression promoted secondary growth and increased xylem production. Further analysis showed that PtoTCP20 interacted with PtoWOX4a and activated PtoWND6 transcription in vitro and in vivo. Our data show that PtoTCP20 controls vascular cambium proliferation by binding to PtoWOX4a, and promotes secondary xylem differentiation by activating PtoWND6 transcription, thereby regulating secondary growth in P. tomentosa. Our findings provide insight into the molecular mechanisms underlying secondary growth in trees.

Background MicroRNAs (miRNAs) play important roles in the development and progression of sepsis. This study investigated the clinical value of miR-19b-3p in sepsis patients, and explored its role in regulating inflammatory responses in HUVECs cells. Methods 103 patients with sepsis and 98 healthy individuals were recruited. qRT-PCR was used for the measurement of miR-19b-3p level. Cell viability was evaluated using CCK-8. The protein levels of TNF-α and IL-6 were measured using ELISA. Receiver operating characteristic (ROC) curve and logistic regression analysis were constructed to evaluate the diagnostic and prognostic values of miR-19b-3p in sepsis patients. Results MiR-19b-3p level was significantly reduced in the serum from patients with sepsis compared with healthy controls (P P P = 0.037). MiR-19b-3p level was negatively associated with serum levels of IL-6 (r = − 0.852, P r = − 0.761, P P Conclusion MiR-19b-3p might be a potential biomarker for the early diagnosis and prognosis of sepsis patients. Overexpression of miR-19b-3p alleviated sepsis-induced inflammatory responses.

We compared plaque characteristics between symptomatic and asymptomatic sides in patients with bilateral carotid vulnerable plaques using magnetic resonance imaging (MRI). Participants (n = 67; mean age: 65.8 ± 7.7 years, 61 males) with bilateral carotid vulnerable plaques were included. Vulnerable plaques were characterized by intraplaque hemorrhage (IPH), large lipid-rich necrotic core (LRNC), or fibrous cap rupture (FCR) on MRI. Symptomatic vulnerable plaques showed greater plaque burden, LRNC volume (median: 221.4 vs 134.8 mm3, P = .003), IPH volume (median: 32.2 vs 22.5 mm3, P = .030), maximum percentage (Max%) LRNC (median: 51.3% vs 41.8%, P = .002), Max%IPH (median: 13.4% vs 9.5%, P = .022), cumulative slices of LRNC (median: 10 vs 8, P = .005), and more juxtaluminal IPH and/or thrombus (29.9% vs 6.0%, P = .001) and FCR (37.3% vs 16.4%, P = .007) than asymptomatic ones. After adjusting for plaque burden, differences in juxtaluminal IPH and/or thrombus (odds ratio [OR]: 5.49, 95% CI: 1.61-18.75, P = .007) and FCR (OR: 2.90, 95% CI: 1.16-7.24, P = .022) between bilateral sides remained statistically significant. For patients with bilateral carotid vulnerable plaques, symptomatic plaques had greater burden, more juxtaluminal IPH and/or thrombus, and FCR compared with asymptomatic ones. The differences in juxtaluminal IPH and/or thrombus and FCR between bilateral sides were independent of plaque burden.

Background: Prediction of protein subcellular location is a meaningful task which attracts much attention in recent years. Particularly, the number of new protein sequences yielded by the highthroughput sequencing technology in the post genomic era has increased explosively. Objective: Protein subcellular localization prediction based solely on sequence data remains to be a challenging problem of computational biology. Methods: In this paper, three sets of evolutionary features are derived from the position-specific scoring matrix, which has shown great potential in other bioinformatics problems. A fusion model is built up by the optimal parameters combination. Finally, principal component analysis and support vector machine classifier is applied to predict protein subcellular localization on NNPSL dataset and Cell- PLoc 2.0 dataset. Results: Our experimental results show that the proposed method remarkably improved the prediction accuracy, and the features derived from PSI-BLAST profile only are appropriate for protein subcellular localization prediction.

miRNAs (microRNAs) are ~ 21-nt non-coding small RNAs (sRNAs) that play crucial regulatory roles in plant biotic and abiotic stress responses. Phosphorus (Pi) deficiency constrains plant growth and reduces yields worldwide. To identify tree miRNAs and evaluate their functions in the response to low Pi, we identified 261 known and 31 candidate novel miRNA families from three sRNA libraries constructed from Populus tomentosa subjected to sufficient or Pi deficiency condition or to restoration of a sufficient Pi level after Pi deficiency. Pi deficiency resulted in significant changes in the abundance of TPM (transcript per million) of 65 known and 3 novel miRNAs. Interestingly, four miRNAs responsive to low N-miR167, miR394, miR171, and miR857-were found to be involved in the response to low Pi. Thirty-five known and one novel miRNAs responded dynamically to Pi fluctuations, suggesting their involvement in the response to Pi deficiency. miRNA clusters comprising 36 miRNAs were identified in 10 chromosomes. Intriguingly, nine pairs of sense and antisense miRNAs transcribed from the same loci were detected in P. tomentosa, which is the first such report in woody plants. Moreover, target genes of the known miRNAs and novel miRNA candidates with significantly changed abundance were predicted, and their functions were annotated. Degradome sequencing supported the identified targets of miRNAs in P. tomentosa. These findings will enhance our understanding of universal and specific molecular regulatory mechanisms of trees under nutrition stress and may facilitate improvement of the Pi utilization efficiency of woody plants.

Sugarcane is a major sugar-producing crop, which contributed 80% of the world’s sugar in 2010. Saccarhum officinarum is a domestic species with high sugar content, while, Saccarhum spontaneum is a wild species with stress tolerance. The highly complex polyploid genome of modern sugarcane cultivars arose from the interspecific hybridization between S. officinarum and S. spontaneum. Sucrose synthase (SUS) is a key enzyme for sucrose metabolism in plants, where activity is bidirectional: both synthetic and separate. In this study, nine genomic sequences of S. officinarum and eight genomic sequences of S. spontaneum for five SUS genes were identified. Phylogenetic analysis showed that the Saccharum SUS3 and SUS5 genes were generated from ρ duplication, SUS1 and SUS2 were duplicated after the split of dicot and monocot species, and SUS4 was retained from the last common ancestor before the origination of Angiospermae. The gene structure and Ka/Ks analysis suggested the functional constraint of SUS genes in the two Saccharum species. Gene expression based on RNA-seq analysis revealed that SUS1was dominantly expressed in source tissues including the internodes and the basal zone of the leaves, SUS2 was detectable in all tissues examined, and the remaining three SUS genes were expressed at low levels in the examined tissues, indicating SUS1 is the key member involved in sucrose accumulation. In addition, SUS genes were observed to be present at higher expression levels in S. officinarum than in S. spontaneum, while SUS2 presented different expression patterns during the circadian rhythm in S. spontaneum and S. officinarum, suggesting the two SUS genes contribute to the differential sugar levels in these species. Our comprehensive study in Saccharum provides the foundations for further functional studies of the SUS gene family.

E3 ubiquitin ligase RNF126 (ring finger protein 126) is highly expressed in various cancers and strongly associated with tumorigenesis. However, its specific function in bladder cancer (BCa) is still debatable. Here, we found that RNF126 was significantly upregulated in BCa tissue by TCGA database, and our studies indicated that downregulation of RNF126 significantly inhibited cell proliferation and metastasis through the EGFR/PI3K/AKT signaling pathway in BCa cells. Furthermore, we identified PTEN, an inhibitor of the PI3K/AKT signaling pathway, as a novel substrate for RNF126. By co-immunoprecipitation assays, we proved that RNF126 directly interacts with PTEN. Predominantly, PTEN binds to the C-terminal containing the RING domain of RNF126. The in vivo ubiquitination assay showed that RNF126 specifically regulates PTEN stability through poly-ubiquitination. Furthermore, PTEN knockdown restored cell proliferation, metastasis, and tumor formation of BCa cells inhibited by RNF126 silencing in vitro and in vivo. In conclusion, these results identified RNF126 as an oncogene that functions through ubiquitination and degradation of PTEN in BCa.

Background Tetracentron sinense is an endemic and endangered deciduous tree. It belongs to the Trochodendrales, one of four early diverging lineages of eudicots known for having vesselless secondary wood. Sequencing and resequencing of the T. sinense genome will help us understand eudicot evolution, the genetic basis of tracheary element development, and the genetic diversity of this relict species. Results Here, we report a chromosome-scale assembly of the T. sinense genome. We assemble the 1.07 Gb genome sequence into 24 chromosomes and annotate 32,690 protein-coding genes. Phylogenomic analyses verify that the Trochodendrales and core eudicots are sister lineages and showed that two whole-genome duplications occurred in the Trochodendrales approximately 82 and 59 million years ago. Synteny analyses suggest that the γ event, resulting in paleohexaploidy, may have only happened in core eudicots. Interestingly, we find that vessel elements are present in T. sinense, which has two orthologs of AtVND7, the master regulator of vessel formation. T. sinense also has several key genes regulated by or regulating TsVND7.2 and their regulatory relationship resembles that in Arabidopsis thaliana. Resequencing and population genomics reveals high levels of genetic diversity of T. sinense and identifies four refugia in China. Conclusions The T. sinense genome provides a unique reference for inferring the early evolution of eudicots and the mechanisms underlying vessel element formation. Population genomics analysis of T. sinense reveals its genetic diversity and geographic structure with implications for conservation.

Background New cell wall imaging tools permit direct visualization of the molecular architecture of cell walls and provide detailed chemical information on wall polymers, which will aid efforts to use these polymers in multiple applications; however, detailed imaging and quantification of the native composition and architecture in the cell wall remains challenging. Results Here, we describe a label-free imaging technology, coherent Raman scattering (CRS) microscopy, including coherent anti-Stokes Raman scattering (CARS) microscopy and stimulated Raman scattering (SRS) microscopy, which can be used to visualize the major structures and chemical composition of plant cell walls. We outline the major steps of the procedure, including sample preparation, setting the mapping parameters, analysis of spectral data, and image generation. Applying this rapid approach will help researchers understand the highly heterogeneous structures and organization of plant cell walls. Conclusions This method can potentially be incorporated into label-free microanalyses of plant cell wall chemical composition based on the in situ vibrations of molecules.

WAP four-disulfide core domain 2 (WFDC2) is a small secretory protein that has been widely studied in ovarian cancer. It has been proven that WFDC2 promotes proliferation and metastasis in ovarian cancer, and serves as a diagnostic biomarker. However, the specific function of WFDC2 in prostate cancer has not been reported. Here, we first screened the diagnostic marker and favorable prognostic factor WFDC2 in prostate cancer by bioinformatics. WFDC2 expression was negatively correlated with Gleason score and metastasis in prostate cancer. Then, we revealed that overexpression of WFDC2, and addition of recombinant protein HE4 can significantly inhibit prostate cancer metastasis in vivo and in vitro. By co-immunoprecipitation and co-localization assays, we proved that WFDC2 binds to the extracellular domain of epidermal growth factor receptor (EGFR). Immunoblot showed that WFDC2 overexpression and recombinant protein HE4 addition inactivated the EGFR/AKT/GSK3B/Snail signaling pathway, and then restrained the progression of epithelial–mesenchymal transition. In conclusion, our study identified that the tumor suppressor WFDC2 can suppress prostate cancer metastasis by inactivating EGFR signaling.

Background: Depression is pervasive in the military context and is likely to elicit lasting negative effects on health. Based on interpersonal models, social-interpersonal stressors are significantly associated with the development and maintenance of depression. However, little is known about the mechanisms by which these stressors increase the risk of depression in terms of social relationships. Rejection sensitivity, which refers to people who are sensitive to social rejection and tend to anxiously expect, readily perceive, and overreact to it, may play an underlying role in this process, as it is formed through social-interpersonal stressors and then aggravates further symptoms of depression. Objectives: The current study aimed to examine the mediating effects on the relationship between social-interpersonal stressors and depressive symptoms in the military context. Methods: This study recruited 600 soldiers aged from 17-36 (M = 21.80; SD = 2.99; 100% males) with a cluster sampling method who completed Social-Interpersonal Stressors subscale, Rejection Sensitivity Questionnaire (RSQ) and Self-Rating Depression Scale (SDS). Mediation analyses examined the underlying mechanism between social-interpersonal stressors and depressive symptoms. Results: The results support the hypothesis and indicate that rejection sensitivity mediates the association between social-interpersonal stressors and depressive symptoms (B indirect = 0.02, p < 0.001, 95% CI= 0.005 to 0.044). Conclusions: The findings suggest that interventions designed to desensitize individuals’ high levels of rejection sensitivity may help to decrease their risk of depressive symptoms in the military environment. Rejection sensitivity is an important mechanism underpinning the development of depressive symptoms. Other theoretical and applied implications for prevention of depressive symptoms in the military context are discussed.

BACKGROUND The relationship between plaque characteristics and their predictive value for perioperative cerebral blood flow (CBF) are unknown. PURPOSE To investigate the relationship between carotid plaque characteristics and perioperative CBF utilizing MRI. STUDY TYPE Prospective. POPULATION In all, 131 patients with carotid moderate-to-severe stenosis referred for carotid endarterectomy (CEA). FIELD STRENGTH/SEQUENCE 3T, black-blood T1 - and T2 -weighted, 3D time-of-flight, and simultaneous noncontrast angiography intraplaque hemorrhage. ASSESSMENT The relative CBF (rCBF = CBFindex-hemisphere /CBFcontralateral-hemisphere ) and the CBF difference ratio (DRCBF = [CBFpost-CEA - CBFpre-CEA ]/CBFpre-CEA ) in the middle cerebral artery territory were measured. The pre- and post-CEA CTP data were used as the assessment standard for CBF change. Carotid lipid-rich necrotic core (LRNC), intraplaque hemorrhage, calcification, fibrous cap rupture, maximum wall thickness, normalized wall index (NWI), and stenosis were determined. STATISTICAL TESTS Pearson or Spearman correlation, Mann-Whitney U-test, and linear regression. RESULTS Patients with LRNC had higher rCBFpre-CEA than those without (1.0 ± 0.1 vs. 0.9 ± 0.1, P

Background It has been proved that multi-contrast cardiovascular magnetic resonance (CMR) vessel wall imaging could be used to characterize carotid vulnerable plaque components according to the signal intensity on different contrast images. The signal intensity of plaque components is mainly dependent on the values of T1 and T2 relaxation. T1 mapping recently showed a potential in identifying plaque components but it is not well validated by histology. This study aimed to validate the usefulness of in vivo T1 mapping in assessing carotid vulnerable plaque components by histology. Methods Thirty-four subjects (mean age, 64.0 ± 8.9 years; 26 males) with carotid plaques referred to carotid endarterectomy were prospectively enrolled and underwent 3 T CMR imaging from May 2017 to October 2017. The T1 values of intraplaque hemorrhage (IPH), necrotic core (NC) and loose matrix (LM) which were identified on multi-contrast vessel wall images or histology were measured on in-vivo T1 mapping. The IPHs were divided into two types based on the proportion of the area of fresh hemorrhage on histology. The T1 values of different plaque components were compared using Mann-Whitney U test and the agreement between T1 mapping and histology in identifying and quantifying IPH was analyzed with Cohen’s Kappa and intraclass correlation coefficient (ICC). Results Of 34 subjects, 19 had histological specimens matched with CMR imaging. The mean T1 values of IPH (651 ± 253 ms), NC (1161 ± 182 ms) and LM (1447 ± 310 ms) identified by histology were significantly different. The T1 values of Type 1 IPH were significantly shorter than that of Type 2 IPH (456 ± 193 ms vs. 775 ± 205 ms, p p p = 0.028) and segmentation (ICC = 0.816, 95% CI 0.679–0.894) of IPHs between T1 mapping and histology. Conclusions The T1 values of carotid plaque components, particularly for intraplaque hemorrhage, are differentiable, and the stage of intraplaque hemorrhage can be classified according to T1 values, suggesting the potential capability of assessment of vulnerable plaque components by T1 mapping.

BACKGROUND Intravenous thrombolysis is the only approved pharmacological treatment for acute ischemic stroke (AIS) patients, but the immediate response to thrombolysis varies by patient. OBJECTIVE To investigate the factors associated with early neurological improvement (ENI) after the administration of intravenous recombinant tissue plasminogen activator (rt-PA) treatment to AIS patients within 4.5 hours of onset. METHODS Demographics, onset to treatment time, risk factors, and clinical and laboratory data of 209 AIS patients undergoing intravenous rt-PA therapy at a Chinese hospital between January 2013 and August 2016 were retrospectively analyzed. The National Institutes of Health Stroke Scale (NIHSS) score was recorded before thrombolytic therapy, 24 hours after the treatment, and 7 days after the treatment to evaluate the recovery of neurological function. ENI was defined as a ≥4-point decrease in NIHSS score compared with baseline or a score of 0 or 1 at 24 hours and 7 days. A multivariate logistic regression analysis was performed to assess the outcomes. RESULTS Of the 209 AIS patients treated by intravenous thrombolysis with rt-PA, low-density lipoprotein (LDL) levels were significantly lower (P

Goldfish have been subjected to over 1,000 y of intensive domestication and selective breeding. In this report, we describe a high-quality goldfish genome (2n = 100), anchoring 95.75% of contigs into 50 pseudochromosomes. Comparative genomics enabled us to disentangle the two subgenomes that resulted from an ancient hybridization event. Resequencing 185 representative goldfish variants and 16 wild crucian carp revealed the origin of goldfish and identified genomic regions that have been shaped by selective sweeps linked to its domestication. Our comprehensive collection of goldfish varieties enabled us to associate genetic variations with a number of well-known anatomical features, including features that distinguish traditional goldfish clades. Additionally, we identified a tyrosine-protein kinase receptor as a candidate causal gene for the first well-known case of Mendelian inheritance in goldfish-the transparent mutant. The goldfish genome and diversity data offer unique resources to make goldfish a promising model for functional genomics, as well as domestication.

Modern sugarcanes are polyploid interspecific hybrids, combining high sugar content from Saccharum officinarum with hardiness, disease resistance and ratooning of Saccharum spontaneum. Sequencing of a haploid S. spontaneum, AP85-441, facilitated the assembly of 32 pseudo-chromosomes comprising 8 homologous groups of 4 members each, bearing 35,525 genes with alleles defined. The reduction of basic chromosome number from 10 to 8 in S. spontaneum was caused by fissions of 2 ancestral chromosomes followed by translocations to 4 chromosomes. Surprisingly, 80% of nucleotide binding site-encoding genes associated with disease resistance are located in 4 rearranged chromosomes and 51% of those in rearranged regions. Resequencing of 64 S. spontaneum genomes identified balancing selection in rearranged regions, maintaining their diversity. Introgressed S. spontaneum chromosomes in modern sugarcanes are randomly distributed in AP85-441 genome, indicating random recombination among homologs in different S. spontaneum accessions. The allele-defined Saccharum genome offers new knowledge and resources to accelerate sugarcane improvement.

Pineapple occupies an important phylogenetic position as its reference genome is a model for studying the evolution the Bromeliaceae family and the crassulacean acid metabolism (CAM) photosynthesis. Here, we developed a pineapple genomics database (PGD, http://pineapple.angiosperms.org/pineapple/html/index.html) as a central online platform for storing and integrating genomic, transcriptomic, function annotation and genetic marker data for pineapple (Ananas comosus (L.) Merr.). The PGD currently hosts significant search tools and available datasets for researchers to study comparative genomics, gene expression, gene co-expression molecular marker, and gene annotation of A. comosus (L). PGD also performed a series of additional pages for a genomic browser that visualizes genomic data interactively, bulk data download, a detailed user manual, and data integration information. PGD was developed with the capacity to integrate future data resources, and will be used as a long-term and open access database to facilitate the study of the biology, distribution, and the evolution of pineapple and the relative plant species. An email-based helpdesk is also available to offer support with the website and requests of specific datasets from the research community.

Background Subcellular localization prediction of protein is an important component of bioinformatics, which has great importance for drug design and other applications. A multitude of computational tools for proteins subcellular location have been developed in the recent decades, however, existing methods differ in the protein sequence representation techniques and classification algorithms adopted. Results In this paper, we firstly introduce two kinds of protein sequences encoding schemes: dipeptide information with space and Gapped k-mer information. Then, the Gapped k-mer calculation method which is based on quad-tree is also introduced. Conclusions >From the prediction results, this method not only reduces the dimension, but also improves the prediction precision of protein subcellular localization.

To investigate the differences in the interactions of microbial communities in two regions in Taihu Lake with different nutrient loadings [Meiliang Bay (MLB) and Xukou Bay (XKB)], water samples were collected and both intra- and inter-kingdom microbial community interactions were examined with network analysis. It is demonstrated that all of the bacterioplankton, microeukaryotes and inter-kingdom communities networks in Taihu Lake were non-random. For the networks of bacterioplankton and inter-kingdom community in XKB, higher clustering coefficient and average degree but lower average path length indexes were observed, indicating the nodes in XKB were more clustered and closely connected with plenty edges than those of MLB. The bacterioplankton and inter-kingdom networks were considerably larger and more complex with more module hubs and connectors in XKB compared with those of MLB, whereas the microeukaryotes networks were comparable and had no module hubs or connectors in the two lake zones. The phyla of Acidobacteria, Cyanobacteria and Planctomycetes maintained greater cooperation with other phyla in XKB, rather than competition. The relationships between microbial communities and environmental factors in MLB were weaker. Compared with the microbial community networks of XKB, less modules in networks of MLB were significantly correlated with total phosphorous and total nitrogen.

Detailed ecological information on ammonia-oxidizing bacteria (AOB) in activated sludge of wastewater treatment plants (WWTPs) is very important to improve the efficiency of wastewater treatment. In this study, activated sludge samples were collected from seven municipal WWTPs located in seven cities in China, and real-time quantitative polymerase chain reaction (qPCR), as well as construction of clone libraries combined with correlation-based data analysis was performed. Further, the effect of geographic distribution and some water quality parameters on the ecological distribution of AOB in activated sludge from WWTPs were investigated. The geographic distribution, the influent concentration of total nitrogen (TN) and ammonia nitrogen (NH4+-N) had significant effects on the abundance of AOB (P < 0.05). However, the community structure of AOB were not significantly affected by geographic distribution, but by water quality parameters including the concentrations of TN and NH4+-N. N. oligotropha lineage was the dominant AOB group in the wastewater treatment systems. The results obtained in this study provide useful information to understand some aspects of the ecological information and influencing factors of AOB in geographically distributed WWTPs.

Summary: Shwachman-Diamond syndrome (SDS) is a rare pediatric disease characterized by various systemic disorders, including hematopoietic dysfunction. The mutation of Shwachman-Bodian-Diamond syndrome (SBDS) gene has been proposed to be a major causative reason for SDS. Although SBDS patients were reported to have shorter telomere length in granulocytes, the underlying mechanism is still unclear. Here we provide data to elucidate the role of SBDS in telomere protection. We demonstrate that SBDS deficiency leads to telomere shortening. We found that overexpression of disease-associated SBDS mutants or knockdown of SBDS hampered the recruitment of telomerase onto telomeres, while the overall reverse transcriptase activity of telomerase remained unaffected. Moreover, we show that SBDS could specifically bind to TPP1 during the S phase of cell cycle, likely functioning as a stabilizer for TPP1-telomerase interaction. Our findings suggest that SBDS is a telomere-protecting protein that participates in regulating telomerase recruitment.

Genome editing (also known as targeted mutation) has promise for molecular breeding. Compared with the CRISPR/Cas9 system, the transcription activator-like effector nucleases (TALENs) have likely a lesser off-target rate in genome editing. Both a rapid test system for the functionality of designed TALENs and an effective delivery system for introducing the TALENs to plants are critical for successful target mutation. TALENs have usually been tested in protoplasts or introduced to plants with viral vectors. However, plant regeneration from protoplast culture can generate extensive somatic variation. Viral vectors are not always available, and plants edited by these vectors usually require virus elimination. Here, we used a non-viral, Agrobacterium-mediated transient expression approach, to serve both rapid test and effective delivery of TALENs into two vegetatively propagated potato cultivars, Solanum tuberosum Russet Burbank and Shepody. Two TALENs with different molecular weights (22 and 27 aa-repeat modules) were expressed to target two endogenous genes (starch branching enzyme and an acid invertase) by Agrobacterium-mediated infiltration (agroinfiltration) into leaves of potato plants. The infiltrated leaf DNA was analyzed using restriction site loss assay and subsequent DNA sequencing. Deep sequencing of these tetraploid cultivars was also conducted to determine the zygosity at the targeted chromosomal loci. TALENs, with different molecular weights, successfully agroinfiltrated and induced mutations at both targeted loci.

Cardiac myxoma (CM) is a prevalent primary cardiac tumor. miR-217 plays a vital role in tumorigenesis of various cancers, however, its role and underlying molecular mechanism in human CM remain poorly understood. Here, we reported that the expression of miR-217 was downregulated in CM tissues and inversely correlated with the expression of Interleukin-6 (IL-6) mRNA. Gain-of-function analysis indicated that overexpression of miR-217 inhibited the proliferation and promoted the apoptosis of the primary CM cells. Bioinformatics analysis showed that IL-6 was a direct target gene of miR-217, which is confirmed by the dual luciferase assays. Moreover, downregulation of IL-6 by small interference RNA (siRNA) mimicked the tumor-suppressive effects of miR-217 in CM. Furthermore, rescue experiments pointed out that restoration of IL-6 expression abrogated the anti-proliferative and pro-apoptotic effect induced by miR-217 overexpression in CM cells. Taken together, we validated that miR-217 could act as a tumor suppressor in CM by directly targeting 3′UTR of IL-6 gene, indicating that manipulation of miR-217 may be a potential therapeutic strategy for CM patients.

In Methanocaldococcus jannaschii, methylglyoxal (MG) is required for aromatic amino acid biosynthesis. Previously, the reduction of MG to lactaldehyde in Methanocaldococcus jannaschii cell extracts using either NADPH or F420 H2 was demonstrated; however, the enzyme responsible was not identified. Using NADPH as the reductant, the unknown enzyme was purified from cell extracts of Methanocaldococcus jannaschii and determined to be the F420 -dependent N5 ,N10 -methylenetetrahydromethanopterin reductase (Mer). Here, we report that the recombinantly overexpressed Mer is able to use NADPH and MG (KM of 1.6 and 1.0 mm, respectively) to produce lactaldehyde. Additionally, Mer does not catalyze the reduction of MG to lactaldehyde in the presence of reduced Fo, the precursor of F420 .

To investigate the differences in the microbial community composition and assembly process in two lake zones (Meiliang Bay (MLB) and Xukou Bay (XKB) in Taihu Lake, China) with different nutrient loadings, water samples were collected. Both the 16S ribosomal RNA (rRNA) gene for the bacterial community and the 18S rRNA gene for the microeukaryote community were investigated using the Illumina second-generation sequencing platform (2 × 250 paired-end). The results indicated that both the bacterioplankton and microeukaryote community composition derived from the two lake zones were significantly different. Significantly higher operational taxonomic unit (OTU) richness (P 0.01) and phylogenetic diversity (P 0.05) were found for the bacterioplankton community of MLB. However, a comparable alpha diversity was found between the microeukaryote communities of MLB and XKB (P 0.05). Environmental factors significantly affected the community compositions in XKB for both the bacterioplankton and microeukaryotes. However, they did not significantly influence the microbial community composition in MLB, except for a weak correlation between dissolved organic carbon (DOC) and the microeukaryote community. The microbial communities tended to be more phylogenetically clustered than expected by chance in the two lake zones. Moreover, the results of the phylogenetic structure suggest that deterministic processes played overwhelming roles in driving the assembly of both the bacterioplankton and microeukaryote community in XKB.

Objectives In this paper, a high-quality sequence encoding scheme is proposed for predicting subcellular location of apoptosis proteins. Methods In the proposed methodology, the novel evolutionary-conservative information is introduced to represent protein sequences. Meanwhile, based on the proportion of golden section in mathematics, position-specific scoring matrix (PSSM) is divided into several blocks. Then, these features are predicted by support vector machine (SVM) and the predictive capability of proposed method is implemented by jackknife test Results The results show that the golden section method is better than no segmentation method. The overall accuracy for ZD98 and CL317 is 98.98% and 91.11%, respectively, which indicates that our method can play a complimentary role to the existing methods in the relevant areas. Conclusions The proposed feature representation is powerful and the prediction accuracy will be improved greatly, which denotes our method provides the state-of-the-art performance for predicting subcellular location of apoptosis proteins.

Mangrove forests are one of the most special forest ecosystems as a hub for marine biotope, yet they are also one of the most threatened and vulnerable ecosystems. Field investigations showed that many populations of Myoporum bontioides (Myoporaceae), a mangrove associate species recorded in southern China, southern Japan and northern Vietnam, have disappeared in China during the recent decades. For the conservation of this species and other related coastal mangrove species, we here report the genetic diversity and population structure of M. bontioides using amplified fragment length polymorphism (AFLP). The analysis produced 1557 polymorphic bands across all the 143 investigated individuals. Our results revealed a relatively high level of genetic diversity (species level: P = 98.90%, He = 0.233, I = 0.451; population level: P = 59.61%, He = 0.171, I = 0.265) and a high level of genetic differentiation (GST = 0.238 and ΦST = 0.316) in M. bontioides. No correlation was observed between genetic distances and geographic distances. A mixed mating system and limited long-distance dispersal ability may partially account for the genetic differentiation. UPGMA dendrogram, PCoA and STRUCTURE analysis revealed a distinct structure of M. bontioides populations. These findings underline that populations of M. bontioides should be preserved in situ, and the Gaoqiao and Taiwan populations should be prioritized for conservation.

Aspirin and clopidogrel are both acceptable antiplatelet options for the secondary prevention of noncardioembolic ischemic stroke. Associations between Essen Stroke Risk Score (ESRS) and antiplatelet treatment in Chinese patients with noncardioembolic ischemic stroke were assessed. This retrospective study was taken in a tertiary care hospital located in eastern China. Patients with noncardioembolic ischemic stroke hospitalized during January 1, 2009, to December 31, 2011, were classified according to ESRS during index stroke hospitalization. Antiplatelet strategy at the time of discharge was categorized as aspirin (100 mg/day) vs. clopidogrel (75 mg/day). Patients received follow-up from July 1, 2014, to December 31, 2015, and the efficacy of clopidogrel and aspirin in different ESRS subgroups was assessed with respect to reducing the risk of a combined vascular event of recurrent stroke, myocardial infarction, or primary intracranial hemorrhage. Totally, 1175 non-cardiac stroke patients were included, among which 878 patients completed follow-up surveys. Of the patients who completed the follow-up, 458 (52.2%) had an ESRS 3, and 621 (70.7%) received aspirin. Patients who received clopidogrel tended to be older, and more patients had hypertension, diabetes, and an ESRS 3 than patients who received aspirin. Over a mean follow-up of 5.2 years, the rate of combined vascular events was 19.3% in the aspirin group and 16.7% in the clopidogrel group. Compared with clopidogrel-treated patients, a significant (P = 0.044) reduction in combined vascular events in aspirin-treated patients was observed in patients with an ESRS ≤ 3 (OR, odds ratio 0.5; 95% CI 0.3 to 0.9). However, a significant (P = 0.002) increase in combined vascular events was observed in patients with an ESRS 3 (OR 2.2; 95% CI 1.3 to 3.8). More clopidogrel-treated patients with ESRS 3 and ESRS = 3 discontinued treatment than their counterparts who took aspirin (P 0.05). Adverse drug events, such as digestive discomfort and bleeding, were similar. In conclusion, clopidogrel is suggested for patients with an ESRS 3 and aspirin for patients with an ESRS ≤ 3 for the secondary prevention of noncardioembolic ischemic stroke in Chinese patients.

Coronary heart disease (CHD) is one of the leading causes of morbidity and mortality worldwide, and more efforts should be made to reduce the risk of cardiovascular events. This study aimed to investigate the impact of clinical pharmacist intervention on the prognosis of acute coronary syndrome (ACS) in Chinese patients with CHD. Two hundred and forty patients who had ACS were recruited. Participants were randomly assigned to the intervention group (n = 120) or the control group (n = 120). The intervention group received a medication assessment and education by the clinical pharmacist at discharge and telephone follow-ups at 1 week and 1 and 3 months after discharge. The control group received usual care. The primary outcomes of this study were the proportion of patients who had major adverse cardiovascular events (MACEs), including mortality, nonfatal myocardial infarction (MI), stroke, and unplanned cardiac-related rehospitalizations within 6 and 12 months after hospital discharge. Secondary outcome was self-reported medication adherence to evidence-based medications for CHD (antiplatelets, statins, β-blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers). Of 240 enrolled patients, 238 (98.3%) completed 6-month follow-up, and 235 (97.9%) completed 12-month follow-up. There were no significant differences between intervention and control groups in the percentages of patients who incurred MACEs within the 6-month follow-up (3.3% vs 7.6%, respectively, P = 0.145) or 12-month follow-up (10.9% vs 12.1%, respectively, P = 0.783). Significant improvements were found in the prescribing rates of β-blockers and all four classes of medications at discharge in the intervention group compared with the control group (P = 0.001 and P = 0.009, respectively). There was no significant difference between the intervention and control groups in the use of all four classes of medications at the 6-month follow-up (48.3% vs 45.8%, respectively, P = 0.691) and 12-month follow-up (47.9% vs 46.6%, respectively, P = 0.836). The use of β-blockers was nonsignificantly higher in the intervention group than in the control group at the 6-month follow-up (74.2% vs. 64.4%, P = 0.103) and 12-month follow-up (74.8% vs 63.8%, P = 0.068). Clinical pharmacist intervention had no significant effects on reduction in cardiovascular events among patients with CHD. Further studies with larger sample sizes and longer time frames for both intervention and follow-up are needed to validate the role of the clinical pharmacist in the morbidity and mortality of CHD. Clinical Trial Registration: chictr.org.cn, identifier ChiCTR-IOR-16007716.

To develop and verify a risk predictive model/scoring system for pulmonary embolism (PE) among hospitalized patients with deep venous thrombosis of the lower extremities (LDVT).776 patients with LDVT were enrolled in a case-control study between January 2016 and June 2017 from the Vascular Surgery Department of Shanxi Dayi Hospital, China. They were randomly divided into development (543 patients, 70%) and validation (233 patients, 30%) databases. Based on the results of pulmonary computed tomography arteriography, patients were divided into 2 categories; those with PE were designated as the case group, whereas those without comprised the controls. A logistic regression model and scoring system for PE in patients with LDVT was established in the development database and verified in the validation database. Scoring system (Shanxi Dayi Hospital score [SDH score]) was tabulated as follows: right lower extremity or bilateral lower extremities, 1; surgery or immobilization, 1; malignant tumor, 1; history of venous thromboembolism (VTE), 2; D-dimer1,000 ng/mL, 2; and unprovoked, 2. Calibration and discrimination of the model were assessed by the Hosmer-Lemeshow goodness of fit test and the area under the receiver operating characteristic curve (AUC). Wells score, the Revised Geneva score, and the SDH score for predictive value of PE by AUC in the validation database were compared.776 patients with LDVT were divided into 2 risk categories based on the scores from the risk model as follows: PE unlikely (score3) and PE likely (score ≥3). Sensitivity, specificity, and crude agreement of the SDH score in the development database were 76.39%, 55.89%, and 61.33%, respectively. In the validation database, the logistic regression model showed good calibration and discriminative power. The Hosmer-Lemeshow goodness of fit test P value was0.05, and the AUC was 0.705 (95% CI: 0.634-0.776, P 0.001). The SDH score also showed good discriminative power, and the AUC was 0.702 (95% CI: 0.631-0.774, P 0.001). Sensitivity, specificity, and crude agreement of the SDH score in the validation database were 67.61%, 61.73%, and 63.52%, respectively. AUC for the Wells score and the Revised Geneva score was 0.611 (95% CI: 0.533-0.688, P = 0.007) and 0.585 (95% CI: 0.503-0.666, P = 0.040), respectively. Difference of the AUC was not statistically significant between the Wells score and the SDH score (0.611 vs. 0.702, P = 0.059) but was so between the Revised Geneva score and the SDH score (0.585 vs. 0.702, P = 0.016). Sensitivity of the Wells score, Revised Geneva score, and the SDH score (64.79%, 67.61% vs. 67.61%) was not statistically significant. However, the specificity of the Wells score and Revised Geneva score was significantly lower than that of the SDH score (48.77%, 39.51% vs. 61.73%).Our logistic regression model and the SDH score based on 7 risk factors as right lower extremity, bilateral lower extremities, unprovoked, surgery or immobilization, malignant tumor, history of VTE, and D-dimer1,000 ng/mL showed good calibration and discriminative power for the assessment of PE risk in patients with LDVT. The SDH score is more specific for PE prediction in the Chinese population, compared with the Wells score and the Revised Geneva score.

Transgenic technology is a powerful tool for gene functional characterization, and poplar is a model system for genetic transformation of perennial woody plants. However, the poplar genetic transformation system is limited to a number of model genotypes. Herein, we developed a transformation system based on efficient Agrobacterium-mediated transformation for the hybrid poplar Populus Alba &times, Populus glandulosa Uyeki, which is a fast-growing poplar species that is suitably grown in the northern part of China. Importantly, we optimized many independent factors and showed that the transformation efficiency was improved significantly using juvenile leaf explants. Explants were infected by an Agrobacterium suspension with the OD600 = 0.6 for 15 min and then co-cultured in dark conditions for 3 days. Using the improved transformation system, we obtained the transgenic poplar with overexpression of &beta, glucuronidase (GUS) via direct organogenesis without callus induction. Furthermore, we analyzed the GUS gene in the transgenic poplars using PCR, qRT-PCR, and GUS staining. These analyses revealed that the GUS gene was efficiently transformed, and it exhibited various expression levels. Taken together, these results represent a simple, fast, and efficient transformation system of hybrid poplar plants. Our findings may facilitate future studies of gene functions in perennial woody plants and tree breeding via transgenic technology assisted design.

Background The decomposition of Microcystis can dramatically change the physicochemical properties of freshwater ecosystems. Bacteria play an important role in decomposing organic matters and accelerating the cycling of materials within freshwater lakes. However, actions of the bacterial community are greatly influenced by temperature and the amount of organic matter available to decompose during a bloom. Therefore, it is vital to understand how different temperatures and biomass levels affect the bacterial community during the decomposition of Microcystis. Results Microcystis addition reduced the diversity of bacterial community. The composition of bacterial community differed markedly between samples with different biomass of Microcystis (no addition, low biomass addition: 0.17 g/L, and high biomass addition: 0.33 g/L). In contrast, temperature factor did not contribute much to the different bacterial community composition. Total nitrogen (TN), total phosphorus (TP), total organic carbon (TOC), ammonia nitrogen (NH4+-N) and oxidation-reduction potential (ORP) were the key measured environmental variables shaping the composition of bacterial community. Conclusions Decomposition of Microcystis changed the physicochemical characteristics of the water and controlled the diversity and composition of the bacterial community. Microcystis biomass rather than temperature was the dominant factor affecting the diversity and composition of the bacterial community. Electronic supplementary material The online version of this article (10.1186/s12866-019-1585-5) contains supplementary material, which is available to authorized users.

An increase in the use of iodinated contrast media, such as iohexol, iodixanol, iopamidol and iopromide, occasionally causes contrast-induced nephropathy (CIN) in patients undergoing coronary angiography (CAG) and/or percutaneous coronary intervention (PCI). The present study aimed to assess the effects of low levels of hemoglobin on the development of CIN in patients with normal renal function following CAG/PCI. A total of 841 consecutive patients undergoing CAG/PCI were divided into two groups: Patients with low levels of hemoglobin (male

Adenine deaminases (Ade) and hypoxanthine/guanine phosphoribosyltransferases (Hpt) are widely distributed enzymes involved in purine salvage. Characterization of the previously uncharacterized Ade (MJ1459 gene product) and Hpt (MJ1655 gene product) are discussed here and provide insight into purine salvage in Methanocaldococcus jannaschii. Ade was demonstrated to use either Fe(II) and/or Mn(II) as the catalytic metal. Hpt demonstrated no detectable activity with adenine, but was equally specific for hypoxanthine and guanine with a kcat /KM of 3.2 × 10(7) and 3.0 × 10(7) s(- 1) M(- 1) , respectively. These results demonstrate that hypoxanthine and IMP are the central metabolites in purine salvage in M. jannaschii for AMP and GMP production. A conserved cysteine (C127, M. jannaschii numbering) was examined due to its high conservation in bacterial and archaeal homologues. To assess the role of this highly conserved cysteine in M. jannaschii Ade, site-directed mutagenesis was performed. It was determined that mutation to serine (C127S) completely abolished Ade activity and mutation to alanine (C127A) exhibited 10-fold decrease in kcat over the wild type Ade. To further investigate the role of C127, detailed molecular docking and dynamics studies were performed and revealed adenine was unable to properly orient in the active site in the C127A and C127S Ade model structures due to distinct differences in active site conformation and rotation of D261. Together this work illuminates purine salvage in M. jannaschii and the critical role of a cysteine residue in maintaining active site conformation of Ade. Proteins 2016; 84:828-840. © 2016 Wiley Periodicals, Inc.

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is rapidly emerging as a life-threatening nosocomial infection. In this study, we aim to identify risk factors, especially antibiotic use, for CRKP infection among intensive care unit (ICU) patients. Methodology: This was a matched case-control study of a 67-bed ICU in a tertiary care teaching hospital from 1 January 2011 through 30 June 2013. The control cases were selected among the patients with carbapenem-susceptible Klebsiella pneumoniae (CSKP) and were matched with CRKP cases for year of ICU admission and site of infection. The clinical outcomes and antibiotic treatments were analyzed. Results: One hundred and thirty patients were included in the study (65 cases and 65 controls). Bivariable analysis showed that age of patients (p = 0.044), number of antibiotic groups (p = 0.001), and exposure to carbapenems (p < 0.001) were associated with CRKP infection. Using multivariate analysis adjusted for age, prior hospitalization, number of antibiotic groups, and previous exposure to carbapenems, previous carbapenem exposure (p < 0.001) was identified as an independent risk factor for CRKP infection. Conclusions: These data suggest that exposure to carbapenems is an independent risk factor for CRKP infection. Patients with this clinical factor should be targeted for interventions to reduce the subsequent risk of infection.

Background Several studies have indicated that high albuminuria is associated with renal function decline. However, the relationship between the urinary albumin-to-creatinine ratio (ACR) and risk of developing tubular injury remains unclear. Our aim was to investigate the association of ACR with the risk of developing tubular impairment in patients with type 2 diabetes. Methods This longitudinal observational study compared baseline with follow-up data in 183 patients with type 2 diabetes. ACR, urinary alpha-1-microglobulin-to-creatinine ratio (A1MCR) and estimated glomerular filtration rate (eGFR) were used to evaluate albuminuira, tubular injury and glomerular filtration function, respectively. Results Levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol and A1MCR were significantly different at the two-year follow-up compared with baseline levels. Among patients both with baseline ACR above and below 30 mg/g, the percentage with A1MCR > 15 mg/g clearly increased after follow-up (P 15 mg/g over the follow-up increased with increasing baseline ACR values lower baseline eGFR. Among the patients with baseline ACR > 63.10 mg/g, all showed increased A1MCR values at follow-up compared with baseline. In the multivariate regression analysis, the patients with baseline ACR > 63.10 mg/g had a strong risk of A1MCR rising from normal to >15 mg/g (odds ratio (OR) = 11.12, P = 0.001) over the follow-up, while the males had a 2.89-fold risk of A1MCR increasing from normal to >15 mg/g compared with females. Conclusion Baseline ACR level is related to increased risk of developing renal tubular injury; in particular, this association is much stronger in patients with type 2 diabetes and baseline ACR > 63.10 mg/g.

The methionine salvage pathway (MSP) is critical for regeneration of S-adenosyl-l-methionine (SAM), a widely used cofactor involved in many essential metabolic reactions. The MSP has been completely elucidated in aerobic organisms, and found to rely on molecular oxygen. Since anaerobic organisms do not use O2, an alternative pathway(s) must be operating. We sought to evaluate whether the functions of two annotated MSP enzymes from Methanocaldococcus jannaschii, a methylthioinosine phosphorylase (MTIP) and a methylthioribose 1-phosphate isomerase (MTRI), are consistent with functioning in a modified anaerobic MSP (AnMSP). We show here that recombinant MTIP is active with six different purine nucleosides, consistent with its function as a general purine nucleoside phosphorylase for both AnMSP and purine salvage. Recombinant MTRI is active with both 5-methylthioribose 1-phosphate and 5-deoxyribose 1-phosphate as substrates, which are generated from phosphororolysis of 5'-methylthioinosine and 5'-deoxyinosine by MTIP, respectively. Together, these data suggest that MTIP and MTRI may function in a novel pathway for recycling the 5'-deoxyadenosine moiety of SAM in M. jannaschii. These enzymes may also enable biosynthesis of 6-deoxy-5-ketofructose 1-phosphate (DKFP), an essential intermediate in aromatic amino acid biosynthesis. Finally, we utilized a homocysteine auxotrophic strain of Methanosarcina acetivorans Δma1821-22Δoahs (HcyAux) to identify potential AnMSP intermediates in vivo. Growth recovery experiments of the M. acetivorans HcyAux were performed with known and proposed intermediates for the AnMSP. Only one metabolite, 2-keto-(4-methylthio)butyric acid, rescued growth of M. acetivorans HcyAux in the absence of homocysteine. This observation may indicate that AnMSP pathways substantially differ among methanogens from phylogenetically divergent genera.

The Arabidopsis shikimate kinase-like 1 (skl1-8) mutant is characterized by a pigment-defective phenotype. Although the related phenotypical defect mainly has been attributed to the blocking of chloroplast development, the molecular functions of SKL1 remain largely unknown. In this study, we combined multiple approaches to investigate the potential functions of SKL1. Results showed that the skl1-8 mutant exhibited an albino phenotype and had dramatically reduced chlorophyll content as a consequence of a single nuclear recessive gene mutation. Chemical complementation analysis indicated that SKL1 does not function as SK enzyme in the shikimate pathway. In addition, by chlorophyll fluorescence parameters and immunoblot analysis, the levels of photosynthetic proteins are substantially reduced. Moreover, by transcriptome analysis, specific groups of nuclear genes involved in photosynthesis, such as light-harvesting complex, pigment metabolism, carbon metabolism, and chloroplast gene expression, were down-regulated, whereas several defense and oxidative stress responsive genes were up-regulated in the skl1-8 mutant compared with the wide type. Furthermore, we found the expression of genes related to auxin transport and response was repressed in the skl1-8 mutant, probable suggesting that SKL1 is involved in auxin-related pathways during chloroplast development. Together, these results provide a useful reference for characterization of SKL1 function during chloroplast biogenesis and development.

Background:Some studies have shown that Human Papillomavirus (HPV) is strongly associated with cervical cancer. As we all know, cervical cancer still remains the fourth most common cancer, affecting women worldwide. Thus, it is both challenging and essential to detect risk types of human papillomaviruses.Methods:In order to discriminate whether HPV type is highly risky or not, many epidemiological and experimental methods have been proposed recently. For HPV risk type prediction, there also have been a few computational studies which are all based on Machine Learning (ML) techniques, but adopt different feature extraction methods. Therefore, we conclude and discuss several classical approaches which have got a better result for the risk type prediction of HPV.Results:This review summarizes the common methods to detect human papillomavirus. The main methods are sequence- derived features, text-based classification, gap-kernel method, ensemble SVM, Word statistical model, position- specific statistical model and mismatch kernel method (SVM). Among these methods, position-specific statistical model get a relatively high accuracy rate (accuracy=97.18%). Word statistical model is also a novel approach, which extracted the information of HPV from the protein “sequence space” with word statistical model to predict high-risk types of HPVs (accuracy=95.59%). These methods could potentially be used to improve prediction of highrisk types of HPVs.Conclusion:From the prediction accuracy, we get that the classification results are more accurate by establishing mathematical models. Thus, adopting mathematical methods to predict risk type of HPV will be the main goal of research in the future.

Our analysis of thousands of movies and books reveals how these cultural products weave stereotypical gender roles into morality tales and perpetuate gender inequality through storytelling. Using the word embedding techniques, we reveal the constructed emotional dependency of female characters on male characters in stories. We call this narrative structure “Cinderella complex”, which assumes that women depend on men in the pursuit of a happy, fulfilling life. Our analysis covers a substantial portion of narratives that shape the modern collective memory, including 7,226 books, 6,087 movie synopses, and 1,109 movie scripts. The “Cinderella complex” is observed to exist widely across periods and contexts, reminding how gender stereotypes are deeply rooted in our society. Our analysis of the words surrounding female and male characters shows that the lives of males are adventure-oriented, whereas the lives of females are romantic-relationship oriented. Finally, we demonstrate the social endorsement of gender stereotypes by showing that gender-stereotypical movies are voted more frequently and rated higher.