Cervicovaginal microbiota long-term dynamics and prediction of different outcomes in persistent human papillomavirus infection.

Persistent human papillomavirus (HPV) infection can lead to cervical intraepithelial neoplasia (CIN) and cervical cancer, posing serious threats to the health of women. Although the cervicovaginal microbiota is strongly associated with CIN, the dynamics of the microbiota during CIN development are unknown. In this retrospective cohort study, we analyzed 3-year longitudinal data from 72 patients diagnosed with a persistent HPV infection almost all caused by high-risk HPV types. Patients were categorized into groups with HPV persistent infection (n = 37), progression to CIN (n = 16), and CIN regression (n = 19) based on infection outcome during the follow-up period. Furthermore, 16S rRNA gene sequencing was performed on consecutively collected cervical samples to explore the composition and dynamics of the cervicovaginal microbiota during the development and regression of CIN. Our results showed that the composition of the cervicovaginal microbiota varied among women with different HPV infection outcomes and remained relatively stable during the follow-up period. Notably, the serial follow-up data showed that these microbial alterations were present for at least 1-2 years and occurred before pathologic changes. In addition, microbial markers that were highly discriminatory for CIN progression or regression were identified. This study provides evidence for a temporal relationship between changes in the cervicovaginal microbiota and the development of CIN, and our findings provide support for future microbial intervention strategies for CIN.

The novel norcantharidin derivative DCZ5417 suppresses multiple myeloma progression by targeting the TRIP13-MAPK-YWHAE signaling pathway.

BACKGROUND: Multiple myeloma (MM), an incurable disease owing to drug resistance, requires safe and effective therapies. Norcantharidin (NCTD), an active ingredient in traditional Chinese medicines, possesses activity against different cancers. However, its toxicity and narrow treatment window limit its clinical application. In this study, we synthesized a series of derivatives of NCTD to address this. Among these compounds, DCZ5417 demonstrated the greatest anti-MM effect and fewest side effects. Its anti-myeloma effects and  the mechanism were further tested. METHODS: Molecular docking, pull-down, surface plasmon resonance-binding, cellular thermal shift, and ATPase assays were used to study the targets of DCZ5417. Bioinformatic, genetic, and pharmacological approaches were used to elucidate the mechanisms associated with DCZ5417 activity. RESULTS: We confirmed a highly potent interaction between DCZ5417 and TRIP13. DCZ5417 inhibited the ATPase activity of TRIP13, and its anti-MM activity was found to depend on TRIP13. A mechanistic study verified that DCZ5417 suppressed cell proliferation by targeting TRIP13, disturbing the TRIP13/YWHAE complex and inhibiting the ERK/MAPK signaling axis. DCZ5417 also showed a combined lethal effect with traditional anti-MM drugs. Furthermore, the tumor growth-inhibitory effect of DCZ5417 was demonstrated using in vivo tumor xenograft models. CONCLUSIONS: DCZ5417 suppresses MM progression in vitro, in vivo, and in primary cells from drug-resistant patients, affecting cell proliferation by targeting TRIP13, destroying the TRIP13/YWHAE complex, and inhibiting ERK/MAPK signaling. These results imply a new and effective therapeutic strategy for MM treatment.

Sensitive colorimetric assay of T4 DNA ligase by the oxidase nanozyme of LaMnO3.26 coupled with a hyperbranched amplification reaction.

The development of efficient methods for the detection of T4 DNA ligase is extremely important for public health. The present work demonstrates the integration of engineerable oxidase nanozyme of LaMnO3.26 nanomaterials for the colorimetric detection of T4 DNA ligase. Specifically, the LaMnO3.26 nanomaterials exhibited oxidase-like activity, oxidizing o-phenylenediamine (OPD), 2,2'-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), and 3,3',5,5'-tetramethylbenzidine (TMB) to their corresponding oxidation products, which featured maximum absorption wavelengths at 450, 417 and 650 nm, respectively, while pyrophosphate ion (PPi) caused an obvious decrease in the oxidase-like activity of LaMnO3.26 through its surface coordination with the surface-exposed Mn element and induced aggregation of the nanozyme. Attributed to the PPi regulated oxidase nanozyme activity, LaMnO3.26 served as a colorimetric probe for the quantitative detection of T4 DNA ligase assisted by a hyperbranched amplification reaction for signal amplification. The T4 DNA ligase was detected with a linear range of 4.8 × 10-3 to 6.0 U mL-1, achieving a detection limit of 1.6 × 10-3 U mL-1. The outcome indicated that the developed nanozyme might be extended to a broad range of practical applications.

Photocatalysis-self-Fenton system over edge covalently modified g-C3N4 with high mineralization of persistent organic pollutants.

The Fenton process is a widely used to remedy organic wastewaters, but it has problems of adding H2O2, low utilization efficiency of H2O2 and low mineralization efficiency. Here, a new photocatalysis-self-Fenton process was exploited for the removal of persistent 4-chlorophenol (4-CP) pollutant through coupling the photocatalysis of 4-carboxyphenylboronic acid edge covalently modified g-C3N4 (CPBA-CN) with Fenton. In this process, H2O2 was in situ generated via photocatalysis over CPBA-CN, the photogenerated electrons assisted the accelerated regeneration of Fe2+ to improve the utilization efficiency of H2O2, and the photogenerated holes facilitated the enhancement of 4-CP mineralization. Under the conjugation of CPBA, the electronic structure of CN was optimized and the molecular dipole was enhanced, resulting in the deepening valence band position, accelerated electron-hole pair separation, and improved O2 adsorption-activation. Therefore, the incremental 4-CP degradation rate in the CPBA-CN photocatalysis-self-Fenton process was approaching 0.099 min-1, by a factor of 3.1 times compared with photocatalysis. The parallel mineralization efficiency increased to 74.6% that was 2.1 and 2.6 times than photocatalysis and Fenton, respectively. In addition, this system maintained an excellent stability in the recycle experiment and can be potentially applied in a wide range of pHs and under the coexistence of various ions. This study would provide new insights for improving Fenton process and promote further development of Fenton in organic wastewater purification.

Integrative analyses of RNA-seq and ChIP-seq Reveal MITF as a Target Gene of TFPI-2 in MDA231 Cells.

Breast cancer is the most prevalent cancer in female patients worldwide. Tissue factor pathway inhibitor 2 (TFPI-2) is identified as an important tumor suppressor in various cancers. Recent studies have shown that TFPI-2 translocates into the nucleus, where it modulates the transcription of the matrix metalloproteinase-2 (MMP-2) gene. However, its biological role and molecular mechanisms in the progression of breast cancer remain unclear. In this study, we identified 5125 differentially expressed genes (DEGs) from RNA sequencing (RNA-seq) in TFPI-2-overexpressing MDA231 cells compared with control cells. Gene ontology and Kyoto encyclopedia of genes and genomes (KEGG) analysis shown that cell cycle, cell differentiation, proteoglycans in cancer, and pathways associated with cancer were highly enriched in downregulated DEGs. Integration of the RNA-seq and ChIP-sequencing (ChIP-seq) data identified 73 genes directly controlled by TFPI-2 in MDA231 cells. Among them, melanocyte inducing transcription factor (MITF) gene expression was repressed by TFPI-2, which was further verified by a luciferase reporter assay and ChIP-quantitative PCR. Our study provides evidence of a novel role of TFPI-2 in human breast cancer involving targeting of the MITF.

Effects of elevated CO2 and warming on the root-associated microbiota in an agricultural ecosystem.

Plant root-associated microbial communities profoundly affect plant nutrition and productivity. Although elevated atmospheric CO2 and warming affect above- and belowground plant processes, it remains unclear how root-associated microbial communities respond to elevated CO2 and warming. In this study, an open-air field experiment was conducted to assay the interactive effects of elevated CO2 (500 ppm) and warming (+2°C) on the root-associated microbiota and soil enzyme activities in a rice-wheat rotation ecosystem. The results revealed that elevated CO2 significantly increased rhizosphere soil organic carbon (SOC) and total nitrogen contents. In addition, glucosidase, ß-xylosidase, and phosphatase activities significantly increased. The richness and Shannon diversity indices were significantly higher in rhizosphere soil than in root endosphere. Elevated CO2 and warming significantly impacted the rhizosphere soil microbiota and altered their composition by changing the relative abundance of some specific groups. Soil pH, SOC, and available potassium content significantly altered the dominant bacterial phyla in the rhizosphere. SOC affected root endophytic bacterial phyla. Bacterial and fungal genera were significantly correlated with soil variables in the rhizosphere than in the root endosphere. These results indicate that microbial communities in the rhizosphere are more sensitive to elevated CO2 and warming than those in the root endosphere.

Subcutaneous immunization with the fusion protein ΔA146Ply-SP0148 confers protection against Streptococcus pneumoniae infection.

Pneumococcal SP0148 and pneumolysin (Ply) derivatives are important vaccine candidates. SP0148 is a conserved lipoprotein with high immunogenicity produced by Streptococcus pneumoniae. We have previously demonstrated that SP0148 can confer protection against fatal infections caused by S. pneumoniae. ΔA146Ply is a noncytotoxic mutant of Ply that retains the TLR4 agonistic effect and has mucosal and subcutaneous adjuvant activities suggested to induce protective immunity against S. pneumoniae infection. In this study, we constructed the fusion protein ΔA146Ply-SP0148, composed of ΔA146Ply and SP0148, and evaluated the immunoprotective effect of the fusion protein. When mice were subcutaneously immunized with the fusion protein ΔA146Ply-SP0148, high levels of anti-ΔA146Ply and anti-SP0148 IgG antibodies were induced in the serum. Specific antibodies can bind to a variety of different serotypes of S. pneumoniae. Compared with mice immunized with ΔA146Ply and SP0148 alone, mice immunized subcutaneously with the fusion protein ΔA146Ply-SP0148 with Al(OH)3 had a higher survival rate when challenged by a lethal dose of S. pneumoniae, and they also had significantly lower lung bacterial loads and milder lung inflammation. In addition, mice immunized subcutaneously with the fusion protein ΔA146Ply-SP0148 stimulated strong Th1, Th2, and Th17 cell responses. In summary, these results suggest that subcutaneous immunization with the ΔA146Ply-SP0148 fusion protein can protect mice against fatal pneumococcal infection and lung infection. The fusion protein ΔA146ply-SP0148 can be a new pneumococcal vaccine target.

Agriterribacter soli sp. nov., isolated from herbicide-contaminated soil.

A Gram-stain-negative, non-spore-forming and rod-shaped bacterium, designated strain NS-102T, was isolated from herbicide-contaminated soil sampled in Nanjing, PR China, and its taxonomic status was investigated by a polyphasic approach. Cell growth of strain NS-102T occurred at 16-42 °C (optimum, 30 °C), at pH 5.0-8.0 (optimum, pH 6.0) and in the presence of 0-3.5 % (w/v) NaCl (optimum, without addition of NaCl). The 16S rRNA gene sequence of strain NS-102T shows high similarity to that of Agriterribacter humi YJ03T (96.9 % similarity), followed by Terrimonas terrae T16R-129T (93.8 %) and Terrimonas pekingensis QHT (93.6 %). Average nucleotide identity, average amino acid identity and digital DNA-DNA hybridization values between the draft genomes of strain NS-102T and A. humi YJ03T were 72.5, 69.4 and 18.6%, respectively. The only respiratory quinone was MK-7, and phosphatidylethanolamine and unidentified lipids were the major polar lipids. The major cellular fatty acids of strain NS-102T contained high amounts of iso-C15 : 0 (24.6 %), iso-C17 : 03-OH (24.1 %), iso-C15 : 0 G (16.6 %) and summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c) (15.6 %). The G+C content of the total DNA was determined to be 40.0 mol%. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this strain from its closest phylogenetic neighbours. Thus, strain NS-102T represents a novel species of the genus Agriterribacter, for which the name Agriterribacter soli sp. nov. is proposed. The type strain is NS-102T (=CCTCC AB 2017249T=KCTC 62322T).

Self-coordinated nanozyme on Cu3BiS3 nanorods for high-performance aptasensing.

A novel strategy is reported to access high-performance nanozymes via the self-coordination of ferrocyanides ([Fe(CN)6]4-) onto the surface of the Cu3BiS3 (CBS) nanorods. Notably, the in situ formed nanozymes had high catalytic activity, good stability, low cost, and easy mass production. The formed nanozyme catalyzed the oxidation of the typical chromogenic substrate of 3,3',5,5'-tetramethylbenzidine (TMB) with a distinctive absorption peak at 652 nm, accompanied by a blue color development. Moreover, the attachment of deoxyribonucleoside 5'-monophosphates (dNMP) beforehand onto the surface of CBS prevented coordination of ferrocyanides and resulted in the tunable formation of the nanozyme, thereby enabling the construction of an exquisite biosensing platform. Taking the aptasensing of chloramphenicol (CAP) as an example, the engineered nanozyme allowed the construction of a homogenous, label-free, and high-performance bioassay in terms of its convenience and high sensitivity. Under the optimal conditions, changes in the absorption intensity at 652 nm for the oxidized TMB provides a good linear correlation with the logarithm of CAP concentrations in the range 0.1 pM to 100 nM, and the limit of detection was 0.033 pM (calculated from 3σ/s). Considering a vast number of bioreactions can be connected to dNMP production, we expect the engineerable nanozyme as a universal signal transduction scaffold for versatile applications in bioassays. Through the attachment of deoxyribonucleoside 5'-monophosphate (dNMP) on the surface of CBS to regulate the generation of self-coordinated nanozyme CBS/BiHCF, a homogeneous, label-free, and high-performance universal aptasensing platform was constructed.

[Genetic diagnosis of a case of Smith-Magenis syndrome due to a rare small-scale deletion].

OBJECTIVE: To report on a case of Smith-Magenis syndrome (SMS) due to a rare small-scale deletion. METHODS: Muscle samples from the the third fetus was collected after the in Medical history and clinical data of the patient were collected. The child and his parents were subjected to chromosome karyotyping analysis, multiplex ligation-dependent probe amplification (MLPA) and copy number variation sequencing (CNV-seq). RESULTS: The child was found to have a normal karyotype. MLPA and CNV-seq detection showed that he has harbored a 1.22 Mb deletion and a 0.3 Mb duplication in the 17p11.2 region. Neither of his parents was found to have similar deletion or duplication. CONCLUSION: The child was diagnosed with SMS due to a rare 1.22 Mb deletion in the 17p11.2 region, which is among the smallest deletions associated with this syndrome.

Invoking Cathodic Photoelectrochemistry through a Spontaneously Coordinated Electron Transporter: A Proof of Concept Toward Signal Transduction for Bioanalysis.

Most of the cathodic photoelectrochemical (PEC) bioassays rely on electron accepting molecules for signal stimuli; unfortunately, the performances of which are still undesirable. New signal transduction strategies are still highly expected for the further development of cathodic photoelectrochemistry as a potentially competitive method. This work represents a new concept of invoked cathodic photoelectrochemistry by a spontaneously formed electron transporter for innovative operation of the sensing strategy. Specifically, the hexacyanoferrate(II) in solution easily self-coordinated with CuO nanomaterials and formed electron transporting copper hexacyanoferrate (CuHCF) on the surface, which endowed improved carrier separation for presenting augmented photocurrent readout. Exemplified by the T4 polynucleotide kinase (T4 PNK) and its inhibitors as targets, a homogenous cathodic PEC biosensing platform was achieved with the distinctive merits of label-free, immobilization-free, and split-mode readout. The mechanism revealed here provided a totally different perspective for signal transduction in cathodic photoelectrochemistry. Hopefully, it may stimulate more interests in the design and construction of semiconductor/transporter counterparts for exquisite operation of photocathodic bioanalysis.

Toyoncin, a Novel Leaderless Bacteriocin That Is Produced by Bacillus toyonensis XIN-YC13 and Specifically Targets B. cereus and Listeria monocytogenes.

Bacteriocins have attracted increasing interest because of their potential as natural preservatives. Recent studies showed that the Bacillus cereus group is a prominent producer of bacteriocins. Using a laboratory-based screening strategy, we identified a strain in the B. cereus group, Bacillus toyonensis XIN-YC13, with antimicrobial activity against B. cereus. A novel, 70-amino-acid-long leaderless bacteriocin, toyoncin, was purified from the culture supernatant of strain XIN-YC13, and its molecular mass was found to be 7,817.1012 Da. Toyoncin shares no similarity with any other known bacteriocins, and its N-terminal amino acid is formylmethionine rather than methionine. Toyoncin shows good pH and heat stability and exhibits specific antimicrobial activity against two important foodborne pathogens, B. cereus and Listeria monocytogenes. Additionally, toyoncin exerts bactericidal activity and induces cell membrane damage. Toyoncin can also inhibit the outgrowth of B. cereus spores. Preservation assays showed that toyoncin effectively suppressed or eradicated B. cereus and L. monocytogenes in pasteurized skim milk. These results suggest that toyoncin can be used as a new biopreservative against B. cereus and L. monocytogenes in the food industry. IMPORTANCE We identified a novel leaderless bacteriocin, toyoncin, produced by B. toyonensis XIN-YC13. Toyoncin shows good pH and heat stability, and it has specific antimicrobial activity against B. cereus and L. monocytogenes (two important foodborne pathogens), likely by destroying their cell membrane integrity. Toyoncin inhibited the outgrowth of B. cereus spores and effectively inhibited or eliminated B. cereus and L. monocytogenes in a milk model system. These results indicate the potential of toyoncin as a food preservative.

Label-free and highly sensitive detection of DNA adenine methylation methyltransferase through cathodic photoelectrochemistry.

In this work, we report the first exploration of cathodic photoelectrochemistry for the determination of the activity of DNA adenine methylation (Dam) methyltransferase (MTase). In this sensing system, potassium ferricyanide (K3[Fe(CN)6]) can greatly stimulate the photocurrent of a CdS quantum dot (QD) sensitized NiO (NiO/CdS) photocathode. After immobilization of the hairpin DNA probe on the electrode surface, its high steric hindrance and the electrostatic repulsion block the access of K3[Fe(CN)6] to the electrode surface, leading to depressed photocurrent of the photocathode. Once the hairpin DNA probe is methylated by Dam MTase, it can be recognized and cleaved by Dpn I, and then further digested by (Exo I), ultimately leading to the removal of the hairpin DNA probe from the electrode surface. This configurational change induces the decrement of steric hindrance/electrostatic repulsion effects and allows the efficient flux of K3[Fe(CN)6] to the photoelectrode for photocurrent stimulation. The cathodic PEC assay is presented in the "turn-on" mode, which can detect Dam MTase in the linear range from 0.04 to 100 U mL-1, with a detection limit as low as 0.028 U mL-1. In principle, the platform presents a promising method for probing various biomolecules that can lead to configuration or charge variations at the electrode surface, which may become a general strategy for versatile targets.

Intercalated doxorubicin acting as stimulator of PbS photocathode for probing DNA-protein interactions.

Label-free and turn-on DNA-binding protein detection based on the doxorubicin (Dox)-intercalated DNA as a signal stimulator in cathodic photoelectrochemistry is reported. The double-stranded DNA (dsDNA) acted as the matrix accommodating the intercalative Dox and allowed its effective photoelectrochemical (PEC) communication with the PbS quantum dots (QDs) for realizing cathodic photocurrent readout. In the presence of the target of the vascular endothelial growth factor (VEGF), the dsDNA was prevented from being digested by the exonuclease III (Exo III), allowing the anchor of Dox to perform as activation stimuli of the photocurrent. The VEGF can be detected in the linear range from 1.5 pM to 100 nM, with an impressively low detection limit of 0.49 pM. This study hints the prospect of DNA intercalated architectures as innovative signaling transduction elements for wide and versatile cathodic PEC bioassays. Effective signaling molecules that are conducive to probe-related cathodic PEC bioassays using DNA as the recognition or signification elements are scarce but very demanding. Herein, the doxorubicin intercalated in duplex DNA functions as an efficient signal stimulator of PbS-consisted photocathode, and thus hints the versatility of the strategy for various targets through cathodic photoelectrochemistry.

Rapid screening for hazelnut oil and high-oleic sunflower oil in extra virgin olive oil using low-field nuclear magnetic resonance relaxometry and machine learning.

BACKGROUND: As extra virgin olive oil (EVOO) has high commercial value, it is routinely adulterated with other oils. The present study investigated the feasibility of rapidly identifying adulterated EVOO using low-field nuclear magnetic resonance (LF-NMR) relaxometry and machine learning approaches (decision tree, K-nearest neighbor, linear discriminant analysis, support vector machines and convolutional neural network (CNN)). RESULTS: LF-NMR spectroscopy effectively distinguished pure EVOO from that which was adulterated with hazelnut oil (HO) and high-oleic sunflower oil (HOSO). The applied CNN algorithm had an accuracy of 89.29%, a precision of 81.25% and a recall of 81.25%, and enabled the rapid (2 min) discrimination of pure EVOO that was adulterated with HO and HOSO in the volumetric ratio range of 10-100%. CONCLUSIONS: LF-NMR coupled with the CNN algorithm is a viable candidate for rapid EVOO authentication. © 2020 Society of Chemical Industry.

First-trimester blood urea nitrogen and risk of gestational diabetes mellitus.

Prior studies indicated that urea increased insulin resistance and higher blood urea nitrogen (BUN) was associated with incident diabetes mellitus. However, it remains unclear whether BUN during the first trimester of pregnancy increases risk of gestational diabetes mellitus (GDM). We aimed to investigate the association between first-trimester BUN and risk of incident GDM. We conducted a prospective, multicenter cohort study of pregnant women. A total of 13 448 eligible pregnant women with measured first-trimester BUN levels were included in this analysis. Logistic regression analysis was used to estimate the relationship between BUN and GDM. Discrimination and reclassification for GDM by BUN were analysed. A total of 2973 (22.1%) women developed GDM. Compared with the lowest quartile of BUN, the third and fourth quartiles were associated with increased risk of GDM (adjusted odds ratios 1.21 [95% CI 1.07-1.37] and 1.50 [95% CI 1.33-1.69], respectively, P for trend <.001). The addition of BUN to conventional factor model improved discrimination (C statistic 0.2%, P = .003) and reclassification (net reclassification index 14.67%, P < .001; integrated discrimination improvement 0.12%, P < .001) for GDM. In conclusion, higher BUN concentrations during the first trimester of pregnancy were associated with increased risk of GDM, suggesting that BUN could be a potential predictor for GDM.

Tespa1 plays a role in the modulation of airway hyperreactivity through the IL-4/STAT6 pathway.

BACKGROUND: Thymocyte-expressed, positive selection-associated 1 (Tespa1) is a critical signaling molecule in thymocyte development. This study aimed to investigate the regulatory effect of Tespa1 on mast cells in the pathogenesis of asthma and its relationship with the interleukin (IL)-4/signal transducers and activators of transcription 6 (STAT6) signaling pathway. METHODS: Tespa1 mRNA expression analysis and IgE levels were carried out using the induced sputum of 33 adults with stable asthma and 36 healthy controls. Tespa1-knockout mice (Tespa1-/-, KO) and C57BL/6 background (wild-type, WT) mice were sensitized and treated with ovalbumin (OVA) to establish an asthma model. Pathological changes, number and activity of mast cells, and changes in activation of the IL-4/STAT6 pathway in lung tissue were detected. The changes of tryptase expression and STAT6 activation after mast cell gene knockout were analyzed in vitro. The changes of enzyme expression and STAT6 activation after mast cell gene knockout were analyzed in vitro. The association between the Tespa1 and p-STAT6 was analyzed by co-immunoprecipitation method. RESULTS: Compared with the healthy controls, Tespa1 expression was decreased, and IgE levels were elevated in the sputum of asthmatic patients. Animal experiments showed that Tespa1-/- mice exhibited more severe inflammation, higher quantity of goblet cells and mast cells in the bronchium, and greater expression of mast cell tryptase, which is induced by ovalbumin, than WT mice. And IL-4, IL-13, phospho-Janus kinase 1, and p-STAT6 expressions presented a higher increase in the Tespa1-/- mouse model than in the WT mouse model. Further in vitro studies confirmed that IL-4 could more significantly promote tryptase and p-STAT6 activities in Tespa1-/- mast cells than their WT counterparts. Correlation analysis results showed a negative correlation between Tespa1 and p-STAT6. Co-immunoprecipitation results demonstrated an association between Tespa1 and p-STAT6. CONCLUSIONS: Altogether, our results indicate that Tespa1 can negatively regulate mast cell activity, and this event is related to the mast cell IL-4/STAT6 signaling pathway and could be therapeutically exploited to treat asthma attacks.

Increased Growth Differentiation Factor 15 Is Associated with Unfavorable Clinical Outcomes of Acute Ischemic Stroke.

BACKGROUND: Growth differentiation factor 15 (GDF-15), a stress-responsive biomarker, is known to be independently associated with mortality and cardiovascular events in different disease settings, but data on the prognostic value of GDF-15 after stroke are limited. METHODS: Baseline serum GDF-15 was measured in 3066 acute ischemic stroke patients from the China Antihypertensive Trial in Acute Ischemic Stroke (CATIS). The primary outcome was a composite of death and major disability within 3 months. Secondary outcomes included death, major disability, vascular events, and stroke recurrence. The associations between GDF-15 and clinical outcomes after stroke were assessed by multivariate logistic regression or Cox proportional hazards models. RESULTS: At 3 months' follow-up, 676 (22.05%), 86 (2.80%), 81 (2.64%), and 51 (1.66%) patients had experienced major disability, death, vascular events, or stroke recurrence, respectively. After adjusting for age, sex, current smoking, alcohol consumption, and baseline National Institutes of Health Stroke Scale score, the odds ratio/hazard ratio (95% CI) of 1 SD higher of base-10 log-transformed GDF-15 was 1.26 (1.15-1.39) for primary outcome, 1.13 (1.02-1.25) for major disability, 1.79 (1.48-2.16) for death, and 1.26 (1.00-1.58) for vascular events. The addition of GDF-15 to established risk factors improved risk prediction of the composite outcome of death and major disability (c-statistic, net reclassification index, and integrated discrimination improvement, all P < 0.05). CONCLUSIONS: High GDF-15 concentrations are independently associated with adverse clinical outcomes of acute ischemic stroke, suggesting that baseline serum GDF-15 could provide additional information to identify ischemic stroke patients at high risk of poor prognosis.

Renal Function Affects Prognostic Role of Antiphosphatidylserine Antibodies for Acute Ischemic Stroke Patients.

BACKGROUND: Whether the renal function influences the association between antiphosphatidylserine antibodies (aPS) and prognosis of ischemic stroke remains unclear. We aimed to investigate the prognostic value of aPS after ischemic stroke stratified by renal function status. METHODS: This prospective study was based on China Antihypertensive Trial in Acute Ischemic Stroke, a randomized clinical trial in 26 hospitals across China from August 2009 to May 2013. A total of 2,874 ischemic stroke patients with blood samples or baseline records of estimated glomerular filtration rate (eGFR) were included in this study. Serum aPS levels were quantitatively measured at baseline, and abnormal renal function in this study was defined as eGFR <90 mL/min per 1.73 m2. The primary outcome was a combination of death and major disability (modified Rankin Scale score ≥3) at 3 months after stroke. Secondary outcomes were death and major disability separately. RESULTS: The association between aPS and primary outcome was significantly modified by renal function status (p for interaction = 0.02). After adjustment for covariates, increased aPS were significantly associated with the primary outcome in the patients with abnormal renal function (OR 2.09; 95% CI 1.24-3.53; p for trend = 0.006), but not in those with normal renal function (OR 0.92; 95% CI 0.69-1.23; p for trend = 0.59), when 2 extreme tertiles were compared. Furthermore, multiple-adjusted spline regression model showed a linear association between aPS and risk of primary outcome in the patients with abnormal renal function (p for linearity = 0.02) but not in those with normal renal function (p for linearity = 0.71). CONCLUSIONS: Increased aPS were positively and independently associated with death or major disability after acute ischemic stroke in the patients with abnormal renal function.

High-throughput photoelectrochemical determination of E. coli O157:H7 by modulation of the anodic photoelectrochemistry of CdS quantum dots via reversible deposition of MnO2.

A method is described for modulating the anodic photoelectrochemistry of netlike CdS quantum dots through the deposition and dissolution of the electron acceptor manganese dioxide (MnO2) on the surface of the photoelectrode. Specifically, the photocurrent of a CdS-modified indium tin oxide (ITO/CdS) electrode is inhibited by chemical deposition of MnO2. However, the photocurrent becomes recovered by oxidative removal of MnO2 with H2O2. This deposition-dissolution reaction modulates the photoelectrochemistry of CdS effectively. A bioassay for Escherichia coli (E. coli) O157:H7 is designed that uses the antimicrobial peptide magainin I as the recognition element. Glucose oxidase (GOx) acts as a catalytic label tracer to produce the signaling molecule H2O2 in the microwell plates. The enzymatically generated H2O2 etches the deposited MnO2 on the photoelectrode and thus enhances the photocurrent. This detection scheme does not cause any damage to biomolecules. It also avoids the adverse effects of immobilized biomolecules for retarding signal production and leads to improved detection when compared to conventional PEC configurations. E. coli can be detected in the 10 to 5.0 × 106 CFU·mL-1 concentration range, and the limit of detection is 3 CFU·mL-1. Graphical abstractSchematic representation of the photoelectrochemical assay of E. coli through the deposition and dissolution of electron accepting manganese dioxide (MnO2) on the surface of the photoelectrode.