Hollow S-Doped ZnFe2O4 Microcubes with Magnetic Separability for Photocatalytic Removal of Uranium(VI) under Different Light Intensity.

Under xenon lamps, ZnFe2O4 (ZFO) has been shown to be effective in removing uranium through photocatalysis. However, its performance is still inadequate in low-light environments due to low photon utilization and high electron-hole complexation. Herein, S-doped hollow ZnFe2O4 microcubes (Sx-H-ZFO, x = 1, 3, 6, 9) were synthesized using the MOF precursor template method. The hollow morphology improves the utilization of visible light by refracting and reflecting the incident light multiple times within the confined domain. S doping narrows the band gap and shifts the conduction band position negatively, which enhances the separation, migration, and accumulation of photogenerated charges. Additionally, S doping increases the number of adsorption sites, ultimately promoting efficient surface reactions. Consequently, Sx-H-ZFO is capable of removing U(VI) in low-light environments. Under cloudy and rainy weather conditions, the photocatalytic rate of S3-H-ZFO was 100.31 µmol/(g·h), while under LED lamps (5000 Lux) it was 72.70 µmol/(g·h). More interestingly, a systematic mechanistic investigation has revealed that S doping replaces some of the oxygen atoms to enhance electron transfers and adsorption of O2. This process initiates the formation of hydrogen peroxide, which reacts directly with UO22+ to form solid studtite (UO2)O2·2H2O. Additionally, the promising magnetic separation capability of Sx-H-ZFO facilitates the recycling and reusability of the material. This work demonstrates the potential of ZnFe2O4 extraction uranium from nuclear wastewater.

Dipole Moment and Built-In Polarization Electric Field Induced by Oxygen Vacancies in BiOX for Boosting Piezoelectric-Photocatalytic Removal of Uranium(VI).

Piezoelectric-photocatalysis is distinguished by its piezoelectricity as an external force that induces deformation within the catalyst to engender a polarized electric field compared to conventional photocatalysis. Herein, the piezoelectric photocatalyst BiOBr has been expertly synthesized via a plasma process and applied for piezoelectric-photocatalysis removal of uranium(VI) for the first time. The abundant surface oxygen vacancies (OVs) could induce a dipole moment and built-in electric field, which endows BiOBr with excellent separation and transport efficiency of photogenerated charges to actuate more charges to participate in the piezoelectric-photocatalytic reduction process. Consequently, under visible light and ultrasound (150 W and 40 kHz), the removal rate constant of OVs-BiOBr-30 (0.0306 min-1) was 2.4, 30.6, and 6 times higher than those of BiOBr (0.01273 min-1), ultrasound, or photocatalysis, respectively. The piezoelectric-photocatalytic synergy is also universal for BiOX (X = Cl, Br, or I) to accelerate the reduction rate of uranium(VI). This work highlights the role of piezoelectric-photocatalysis in the treatment of uranium-containing wastewater, which is of great significance for resource conservation and environmental remediation.

Open-Framework Vanadate as Efficient Ion Exchanger for Uranyl Removal.

The elimination of uranium from radioactive wastewater is crucial for the safe management and operation of environmental remediation. Here, we present a layered vanadate with high acid/base stability, [Me2NH2]V3O7, as an excellent ion exchanger capturing uranyl from highly complex aqueous solutions. The material possesses an indirect band gap, ferromagnetic characteristic and a flower-like morphology comprising parallel nanosheets. The layered structure of [Me2NH2]V3O7 is predominantly upheld by the H-bond interaction between anionic framework [V3O7]nn- and intercalated [Me2NH2]+. The [Me2NH2]+ within [Me2NH2]V3O7 can be readily exchanged with UO22+. [Me2NH2]V3O7 exhibits high exchange capacity (qm = 176.19 mg/g), fast kinetics (within 15 min), high removal efficiencies (>99%), and good selectivity against an excess of interfering ions. It also displays activity for UO22+ ion exchange over a wide pH range (2.00-7.12). More importantly, [Me2NH2]V3O7 has the capability to effectively remove low-concentration uranium, yielding a residual U concentration of 13 ppb, which falls below the EPA-defined acceptable limit of 30 ppb in typical drinking water. [Me2NH2]V3O7 can also efficiently separate UO22+ from Cs+ or Sr2+ achieving the highest separation factors (SFU/Cs of 589 and SFU/Sr of 227) to date. The BOMD and DFT calculations reveal that the driving force of ion exchange is dominated by the interaction between UO22+ and [V3O7]nn-, whereas the ion exchange rate is influenced by the mobility of UO22+ and [Me2NH2]+. Our experimental findings indicate that [Me2NH2]V3O7 can be considered as a promising uranium scavenger for environmental remediation. Additionally, the simulation results provide valuable mechanistic interpretations for ion exchange and serve as a reference for designing novel ion exchangers.

Predictive Value of NT-proBNP for New-onset Atrial Fibrillation in the Acute Phase of Myocardial Infarction.

Objective: The objective of this study was to assess the predictive value of N-terminal pro-brain natriuretic peptide (NT-pro-BNP) levels on admission and new-onset atrial fibrillation (AF) in patients with acute myocardial infarction (AMI). Methods: In this study, a retrospective cohort study design scheme was used to include a total of 291 consecutive patients who were hospitalized for AMI from July 2019 to May 2020, of whom 36 (12.4%) developed new-onset atrial fibrillation (AF) during their hospitalization, which was classified as the AF group, and the rest of the patients were in the non-AF group. The impact of NT-pro-BNP on new-onset atrial fibrillation was investigated using the general data, laboratory tests, cardiac ultrasonography, and coronary angiography results of the two groups. Logistic regression analysis was employed to investigate the effect of NT-pro-BNP on new-onset atrial fibrillation. Additionally, we analyzed the significance of NT-pro-BNP in predicting new-onset AF in AMI patients using the the area under the AUC. Results: Univariate analysis indicated that patients in the AF group had significantly higher (P < .05) age, leukocyte count on admission, high-sensitivity C-reactive protein (hs-CRP), blood creatinine, uric acid, NT-pro-BNP, and left ventricular end-diastolic internal diameter (LVED) than those in the non-AF group. Patients in the AF group had lower blood pressure and left ventricular ejection fraction compared with the non-AF group. Logistic multifactorial regression analysis indicated that NT-pro-BNP was an independent risk factor for new-onset AF in patients with AMI (OR=2.752, 95% CI 1.352-5.602, P = .005). The area under the AUC was 0.747 (95% CI 0.655-0.84; P = .001), with a sensitivity of 64%, a specificity of 78%, and a Jordon's index of 0.458. This corresponds to an optimal cutoff value of 5374 pg/ml, suggesting that NT-pro-BNP performs well in predicting new-onset atrial fibrillation. Conclusion: NT-pro-BNP on admission can be a useful predictor of whether new-onset atrial fibrillation occurs in patients with AMI, with good predictive value. This finding helps better to meet patients' diagnostic and therapeutic needs and provides useful clinical guidance to improve the management and prognosis of AMI patients.

Biomimetic Photocatalytic System Designed by Spatially Separated Cocatalysts on Z-scheme Heterojunction with Identified Charge-transfer Processes for Boosting Removal of U(VI).

Designing highly efficient photocatalysts with rapid migration of photogenerated charges and surface reaction kinetics for the photocatalytic removal of uranium (U(VI)) from uranium mine wastewater remains a significant challenge. Inspired by natural photosynthesis, a biomimetic photocatalytic system is assembled by designing a novel hollow nanosphere MnOx @TiO2 @CdS@Au (MTCA) with loading MnOx and Au nano particles (Au NPs) cocatalysts on the inner and outer surfaces of the TiO2 @CdS. The spatially separated cocatalysts efficiently drive the photogenerated charges to migrate in opposite directions, while the Z-scheme heterogeneous shell further separates the interfacial charges. Theoretical calculation identifies multiple consecutive forward charge transfers without charge recombination within MTCA. Thus, MTCA could efficiently remove 99.61% of U(VI) after 15 min of simulated sunlight irradiation within 3 mmol L-1 NaHCO3 with 0.231 min-1 of the reduction rate constant, outperforming most previously reported photocatalysts. MTCA further significantly removes 91.83% of U(VI) from the natural uranium mining wastewater under sunlight irradiation. This study provides a novel approach to designing an ideal biomimetic photocatalyst for remediating environmental pollution.

Identification and integrated analysis of lncRNAs and miRNAs in IPEC-J2 cells provide novel insight into the regulation of the innate immune response by PDCoV infection.

BACKGROUND: Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), are pivotal regulators involved in the pathogenic mechanism of multiple coronaviruses. Porcine deltacoronavirus (PDCoV) has evolved multiple strategies to escape the innate immune response of host cells, but whether ncRNAs are involved in this process during PDCoV infection is still unknown. RESULTS: In this study, the expression profiles of miRNAs, lncRNAs and mRNAs in IPEC-J2 cells infected with PDCoV at 0, 12 and 24 hours postinfection (hpi) were identified through small RNA and RNA sequencing. The differentially expressed miRNAs (DEmiRNAs), lncRNAs (DElncRNAs) and mRNAs (DEmRNAs) were screened from the comparison group of IPEC-J2 cells at 0 and 12 hpi as well as the comparison group of IPEC-J2 cells at 12 and 24 hpi. The target genes of these DEncRNAs were predicted. The bioinformatics analysis of the target genes revealed multiple significantly enriched functions and pathways. Among them, the genes that were associated with innate immunity were specifically screened. The expression of innate immunity-related ncRNAs and mRNAs was validated by RT-qPCR. Competing endogenous RNA (ceRNA) regulatory networks among innate immunity-related ncRNAs and their target mRNAs were established. Moreover, we found that the replication of PDCoV was significantly inhibited by two innate immunity-related miRNAs, ssc-miR-30c-3p and ssc-miR-374b-3p, in IPEC-J2 cells. CONCLUSIONS: This study provides a data platform to conduct studies of the pathogenic mechanism of PDCoV from a new perspective and will be helpful for further elucidation of the functional role of ncRNAs involved in PDCoV escaping the innate immune response.

Breeding for disease resistance in soybean: a global perspective.

KEY MESSAGE: This review provides a comprehensive atlas of QTLs, genes, and alleles conferring resistance to 28 important diseases in all major soybean production regions in the world. Breeding disease-resistant soybean [Glycine max (L.) Merr.] varieties is a common goal for soybean breeding programs to ensure the sustainability and growth of soybean production worldwide. However, due to global climate change, soybean breeders are facing strong challenges to defeat diseases. Marker-assisted selection and genomic selection have been demonstrated to be successful methods in quickly integrating vertical resistance or horizontal resistance into improved soybean varieties, where vertical resistance refers to R genes and major effect QTLs, and horizontal resistance is a combination of major and minor effect genes or QTLs. This review summarized more than 800 resistant loci/alleles and their tightly linked markers for 28 soybean diseases worldwide, caused by nematodes, oomycetes, fungi, bacteria, and viruses. The major breakthroughs in the discovery of disease resistance gene atlas of soybean were also emphasized which include: (1) identification and characterization of vertical resistance genes reside rhg1 and Rhg4 for soybean cyst nematode, and exploration of the underlying regulation mechanisms through copy number variation and (2) map-based cloning and characterization of Rps11 conferring resistance to 80% isolates of Phytophthora sojae across the USA. In this review, we also highlight the validated QTLs in overlapping genomic regions from at least two studies and applied a consistent naming nomenclature for these QTLs. Our review provides a comprehensive summary of important resistant genes/QTLs and can be used as a toolbox for soybean improvement. Finally, the summarized genetic knowledge sheds light on future directions of accelerated soybean breeding and translational genomics studies.

The pathogens of secondary infection in septic patients share a similar genotype to those that predominate in the gut.

BACKGROUND: Secondary nosocomial infections, which are commonly caused by carbapenem-resistant Klebsiella pneumoniae (CRKP) and vancomycin-resistant Enterococcus faecium (VRE), often develop in septic patients. This study aimed to identify the origin of secondary systemic pathogens and reveal the underlying mechanism of infection. METHODS: In this prospective, observational case-control study, a total of 34 septic patients, 33 non-septic intensive care unit (ICU) patients and 10 healthy individuals serving as controls were enrolled. Three hundred and twelve fecal samples were collected and subjected to 16S rRNA gene amplicon sequencing. Metagenome sequencing was performed to identify the homology between dominant CRKP or VRE in the intestine and pathogens isolated from secondary infectious sites. C57/BL mice were established as pseudo germ-free animal model by pretreatment with broad-spectrum antibiotics for two weeks. RESULTS: The abundance and diversity of the gut microbiota in septic patients was drastically decreased one week after ICU admission, potentially leading to the enrichment of antibiotic-resistant bacteria, such as CRKP. Furthermore, secondary bloodstream and abdominal infections caused by CRKP or VRE in septic patients occurred after intestinal colonization with the predominant bacterial species. Genomic analysis showed that bacteria isolated from secondary infection had high homology with the corresponding predominant intestinal opportunistic pathogens. In addition, animal model experiments validated the hypothesis that the administration of antibiotics caused the enrichment of CRKP and VRE among the intestinal microbiota, increasing the likelihood of permeation of other tissues and potentially causing subsequent systemic infection in pseudo germ-free mice. CONCLUSION: Our study indicated that the pathogens causing secondary infection in septic patients might originate from the intestinal colonization of pathogens following broad-spectrum antibiotic treatment.

Structural Evolution of Polyglycolide and Poly(glycolide-co-lactide) Fibers during the Heat-Setting Process.

PGA and P(GA-co-LA) fibers applied as surgical sutures strongly depend on their microstructure. The structural evolution in both the relaxed and tensioned states during heat-setting after hot stretching, which included heating and postannealing, was investigated using in situ WAXD/SAXS and DSC techniques. We found that the fibers of both PGA and P(GA-co-LA) with 8% LA content under the relaxed state were more advantageous than the fibers under the tensioned state indicated by the larger crystallite sizes and unit cell parameters and the higher crystallinity. The mechanical properties of the samples increased after heat-setting. Heat-setting at 120 °C was more suitable for promoting the fiber properties, which can be ascribed to crystal formation and perfection. During the heating, the thermal expansion increased the unit cell parameters and the long period of PGA linearly, whereas the unit cell parameters of P(GA-co-LA) had an obvious turning point at 60-80 °C, and the long period showed a sudden decline in the temperature range of 60-80 °C, which was mainly the result of the discharge of LA units. The unit cell parameters and the long period of both PGA and P(GA-co-LA) decreased during the isotherm process due to crystal perfection. However, the P(GA-co-LA) decrease was more prominent than PGA because of the inclusion of LA monomers in the crystal structure of GAs.

Metabolomics Profiling Reveals Rehmanniae Radix Preparata Extract Protects against Glucocorticoid-Induced Osteoporosis Mainly via Intervening Steroid Hormone Biosynthesis.

Rehmanniae Radix Preparata (RR), the dry rhizome of Rehmannia glutinosa Libosch., is a traditional herbal medicine for improving the liver and kidney function. Ample clinical and pharmacological experiments show that RR can prevent post-menopausal osteoporosis and senile osteoporosis. In the present study, in vivo and in vitro experiments, as well as a UHPLC-Q/TOF-MS-based metabolomics study, were used to explore the preventing effect of RR on glucocorticoid-induced osteoporosis (GIOP) and its underlying mechanisms. As a result, RR significantly enhanced bone mineral density (BMD), improved the micro-architecture of trabecular bone, and intervened in biochemical markers of bone metabolism in dexamethasone (DEX)-treated rats. For the in vitro experiment, RR increased the cell proliferation and alkaline phosphatase (ALP) activity, enhanced the extracellular matrix mineralization level, and improved the expression of runt-related transcription factor 2 (RUNX2) and osteopontin (OPN) in DEX-injured osteoblasts. For the metabolomics study, a total of 27 differential metabolites were detected in the DEX group vs. the control group, of which 10 were significantly reversed after RR treatment. These metabolites were majorly involved in steroid hormone biosynthesis, sex steroids regulation, and amino acid metabolism. By metabolic pathway and Western blotting analysis, it was further ascertained that RR protected against DEX-induced bone loss, mainly via interfering steroid hormone biosynthesis, as evidenced by the up-regulation of cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1), and the down-regulation of 11ß-hydroxysteroid dehydrogenase (HSD11B1). Collectively, these results indicated that RR had a notable preventing effect on GIOP, and the action mechanism might be related to steroid hormone biosynthesis.

Soybean (Glycine max) WRINKLED1 transcription factor, GmWRI1a, positively regulates seed oil accumulation.

Soybean is the world's most important leguminous crop producing high-quality protein and oil. Elevating oil accumulation in soybean seed is always many researchers' goal. WRINKLED1 (WRI1) encodes a transcription factor of the APETALA2/ethylene responsive element-binding protein (AP2/EREBP) family that plays important roles during plant seed oil accumulation. In this study, we isolated and characterized three distinct orthologues of WRI1 in soybean (Glycine max) that display different organ-specific expression patterns, among which GmWRI1a was highly expressed in maturing soybean seed. Electrophoretic mobility shift assays and yeast one-hybrid experiments demonstrated that the GmWRI1a protein was capable of binding to AW-box, a conserved sequence in the proximal upstream regions of many genes involved in various steps of oil biosynthesis. Transgenic soybean seeds overexpressing GmWRI1a under the control of the seed-specific napin promoter showed the increased total oil and fatty acid content and the changed fatty acid composition. Furthermore, basing on the activated expressions in transgenic soybean seeds and existence of AW-box element in the promoter regions, direct downstream genes of GmWRI1a were identified, and their products were responsible for fatty acid production, elongation, desaturation and export from plastid. We conclude that GmWRI1a transcription factor can positively regulate oil accumulation in soybean seed by a complex gene expression network related to fatty acid biosynthesis.

Effect of continuous positive airway pressure on long-term cardiovascular outcomes in patients with coronary artery disease and obstructive sleep apnea: a systematic review and meta-analysis.

BACKGROUND: Obstructive sleep apnea (OSA) is highly prevalent in patients with coronary artery disease (CAD) and is associated with recurrent cardiovascular risk. However, whether treatment with continuous positive airway pressure (CPAP) reduces this risk remains unclear. We performed a systematic review and meta-analysis to assess the effect of CPAP on long-term cardiovascular outcomes in patients with concomitant CAD and OSA. METHODS: We searched the PubMed, EMBASE, and Cochrane library from their inceptions to October 7, 2017. We included observational studies and randomized controlled trials (RCTs) that described the association of CPAP treatment with cardiovascular events in patients with CAD and OSA. The primary outcome of interest was major adverse cardiovascular event (MACE), including all-cause or cardiovascular death, myocardial infarction, stroke, repeat revascularization, or hospitalization for heart failure. Outcomes data were pooled using random effects models and heterogeneity assessed with the I2 statistic. RESULTS: We identified 9 studies (2 RCTs and 7 observational studies) with 1430 participants. The median follow-up duration was from 36 to 86.5 months. Treatment with CPAP was associated with a significantly lower risk of MACE in 6 observational studies (RR 0.61, 95% CI: 0.39-0.94, P = 0.02), but this was not reproduced in 2 RCTs (RR 0.57, 95% CI: 0.32-1.02, P = 0.06). Similarly, CPAP significantly reduced the risk of all-cause death (4 observational studies) and cardiovascular death (3 observational studies), which were also not confirmed in RCTs. CONCLUSIONS: The use of CPAP in patients with CAD and OSA might prevent subsequent cardiovascular events, which was only demonstrated in observational studies, but not in RCTs. The value of CPAP therapy as second prevention for CAD needs further investigation.

Plasmids of Diverse Inc Groups Disseminate the Fosfomycin Resistance Gene fosA3 among Escherichia coli Isolates from Pigs, Chickens, and Dairy Cows in Northeast China.

Thirty-nine fosfomycin-resistant Escherichia coli isolates carrying fosA3 were obtained from pigs, chickens, dairy cows, and staff in four northeastern provinces of China between June 2015 and April 2016. The fosA3 gene was colocated with blaCTX-M genes on conjugative plasmids of the incompatibility groups IncN (n = 12), IncN-F33:A-:B-(n = 2), IncF33:A-:B-(n = 14), IncF14:A-:B-(n = 2), and IncI1/sequence type 136 (ST136) (n = 9). Four different genetic contexts of fosA3 were detected among the 39 E. coli isolates. Three potential epidemic plasmids circulated among E. coli strains from this region.

Cytochrome P450 reaction phenotyping and inhibition and induction studies of pinostrobin in human liver microsomes and hepatocytes.

Pinostrobin (PI, 5-hydroxy-7-methoxyflavanone) is a natural flavonoid known for its rich pharmacological activities. The objective of this study was to identify the human liver cytochrome P450 (CYP450) isoenzymes involved in the metabolism of PI. A single hydoxylated metabolite was obtained from PI after an incubation with pooled human liver microsomes (HLMs). The relative contributions of different CYP450s were evaluated using CYP450-selective inhibitors in HLMs and recombinant human CYP450 enzymes, and the results revealed the major involvement of CYP1A2, CYP2C9 and CYP2E1 in PI metabolism. We also evaluated the ability of PI to inhibit and induce human cytochrome P450 enzymes in vitro. High-performance liquid chromatography and liquid chromatography-tandem mass spectrometry analytical techniques were used to estimate the enzymatic activities of seven drug-metabolizing CYP450 isozymes in vitro. In HLMs, PI did not inhibit CYP 1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6 or CYP3A4 (IC50 > 100 µm). In the induction studies, PI had minimal effects on CYP1A2, CYP2B6and CYP3A4 activity. Based on these results, PI would not be expected to cause clinically significant CYP450 inhibition or induction.

Novel conjugative plasmid from Escherichia coli of swine origin that coharbors the multiresistance gene cfr and the extended-spectrum-ß-lactamase gene blaCTX-M-14b.

Two porcine Escherichia coli isolates harbored the cfr gene on conjugative plasmids of 38,405 bp (pGXEC6) and 41,646 bp (pGXEC3). In these two plasmids, the cfr gene was located within a 4,612-bp region containing a tnpA-IS26-cfr-IS26-Δhyp element. Plasmid pGXEC3 was almost identical to pGXEC6 except for a 3,235-bp ISEcp1-blaCTX-M-14b insertion. The colocation of the multiresistance cfr gene with an extended-spectrum-ß-lactamase gene on a conjugative plasmid may support the dissemination of these genes by coselection.

Novel plasmid-borne multidrug resistance gene cluster including lsa(E) from a linezolid-resistant Enterococcus faecium isolate of swine origin.

A novel nonconjugative plasmid of 28,489 bp from a porcine linezolid-resistant Enterococcus faecium isolate was completely sequenced. This plasmid harbored a novel type of multiresistance gene cluster that comprised the resistance genes lnu(B), lsa(E), spw, aadE, aphA3, and two copies of erm(B), which account for resistance to macrolides, lincosamides, streptogramins, pleuromutilins, streptomycin, spectinomycin, and kanamycin/neomycin. Structural comparisons suggested that this plasmid might have developed from other enterococcal plasmids by insertion element (IS)-mediated interplasmid recombination processes.

Diagnostic and prognostic utility of tissue factor for severe sepsis and sepsis-induced acute lung injury.

BACKGROUND: Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) play a central role in the endothelial permeability regulation and dysfunction, which is associated with the development of sepsis and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). The aim of this study is to assess the diagnostic and prognostic values of TF and TFPI in patients with sepsis and sepsis-induced ARDS. METHODS: A total of 62 patients with sepsis, 167 patients with severe sepsis and 32 healthy volunteers were enrolled in this prospective observational study. TF and TFPI levels were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Patients with sepsis-induced ARDS showed significantly higher median levels of TF compared with patients without ARDS (1425.5 (1019.9 to 2595.2) pg/ml vs 916.2 (724.1 to 1618.2) pg/ml, P < 0.001), and compared with sepsis patients (943.5 (786.4 to 992.4) pg/ml, P < 0.001) on the day of admission. However, there was no significant difference between sepsis patients and healthy subjects, or between septic shock and non-septic shock patients (P > 0.05). The AUC of TF for the diagnosis of sepsis-induced ARDS was 0.749 (95% confidence interval (CI) 0.675-0.822). Plasma TF levels in the non-survivors of severe sepsis were significantly higher than those of survivors (1618.6 (1017.1 to 2900.8) pg/ml vs. 979.9 (757.2 to 1645.5) pg/ml, P < 0.001), and multivariate logistic regression showed the plasma value of TF was the independent predictor for 30-day mortality in patients with severe sepsis (P = 0.0022, odds ratio (OR) = 1.41, 95% CI 1.24-1.69). The AUC of TF for predicting 30-day mortality in severe sepsis patients was 0.718 (95% CI 0.641-0.794). However, there was no significant difference in the plasma TFPI values among the healthy control, sepsis and severe sepsis groups (P > 0.05). CONCLUSIONS: Our data showed that tissue factor is a valuable diagnostic biomarker for the diagnosis of sepsis-induced ARDS. Moreover, tissue factor is a strong prognostic marker for short-term mortality in severe sepsis and sepsis-induced ARDS patients.

Genetic variation in the tissue factor gene is associated with clinical outcome in severe sepsis patients.

INTRODUCTION: Activation of inflammation and coagulation was closely related and mutually interdependent in sepsis. Tissue factor (TF) and its endogenous inhibitor, tissue factor pathway inhibitor (TFPI) was the main regulators of the initiation of coagulation process. Altered plasma levels of TF and TFPI have been related to worse outcome in sepsis. The objective of this study was to investigate whether single nucleotide polymorphisms (SNPs) in the TF and TFPI genes were associated with risk and outcome for patients with severe sepsis. METHODS: Seventeen SNPs in TF and TFPI were genotyped in samples of sepsis (n =577) and severe sepsis patients (n =476), and tested for association in this case-control collection. We then investigated correlation between the associated SNPs and the mRNA expression, and protein level of the corresponding gene. The mRNA levels of TF were determined using real-time quantitative reverse transcription-polymerase chain reaction and the soluble plasma levels of TF were measured using enzyme linked immunosorbent assay (ELISA) method. RESULTS: Association analysis revealed that three TF SNPs in perfect linkage disequilibrium, rs1361600, rs3917615 and rs958587, were significantly associated with outcome of severe sepsis. G allele frequency of rs1361600 in survivor patients was significantly higher than that in nonsurvivor severe sepsis patients (P =4.91 × 10(-5), odds ratio (OR) =0.48, 95% confidence interval (CI) 0.33 to 0.69). The association remained significant after adjustment for covariates in multiple logistic regression analysis and for multiple comparisons. Lipopolysaccharide-induced TF-mRNA expression levels in peripheral blood mononuclear cells from subjects carrying rs1361600 AG and GG genotypes, were significantly lower than those subjects carrying AA genotype (P =0.0012). Moreover, severe sepsis patients of GG and GA genotypes showed lower serum levels of TF than patients with AA genotype (P adj =0.02). The plasma levels of TF were also associated with outcome of severe sepsis patients (P adj =0.01). However, genotype and allele analyses did not show any significant difference between sepsis and severe sepsis patients. CONCLUSIONS: Our findings indicate that common genetic variation in TF was significantly associated with outcome of severe sepsis in Chinese Han population.

Novel interacting proteins identified by tandem affinity purification and mass spectrometry associated with IFITM3 protein during PDCoV infection.

Interferon-induced transmembrane 3 (IFITM3) is a membrane-associated protein that exhibits antiviral activities against a wide range of viruses through interactions with other cellular and viral proteins. However, knowledge of the mechanisms of IFITM3 in Porcine deltacoronavirus (PDCoV) infection has been lacking. In this study, we demonstrate that IFN-α treatment induces the upregulation of IFITM3 activity and thus attenuates PDCoV infection. PDCoV replication is inhibited in a dose-dependent manner by IFITM3 overexpression. To clarify the novel roles of IFITM3 during PDCoV infection, proteins that interact with IFITM3 were screened by TAP/MS in an ST cell line stably expressing IFITM3 via a lentivirus. We identified known and novel candidate IFITM3-binding proteins and analyzed the protein complexes using GO annotation, KEGG pathway analysis, and protein interaction network analysis. A total of 362 cellular proteins associate with IFITM3 during the first 24 h post-infection. Of these proteins, the relationship between IFITM3 and Rab9a was evaluated by immunofluorescence colocalization analysis using confocal microscopy. IFITM3 partially colocalized with Rab9a and Rab9a exhibited enhanced colocalization following PDCoV infection. We also demonstrated that IFITM3 interacts specifically with Rab9a. Our results considerably expand the protein networks of IFITM3, suggesting that IFITM3 participates in multiple cellular processes during PDCoV infection.