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This paper studies computational methods for quasi-stationary distributions (QSDs). We first proposed a data-driven solver that solves Fokker–Planck equations for QSDs. Similar to the case of Fokker–Planck equations for invariant probability measures, we set up an optimization problem that minimizes the distance from a low-accuracy reference solution, under the constraint of satisfying the linear relation given by the discretized Fokker–Planck operator. Then we use coupling method to study the sensitivity of a QSD against either the change of boundary condition or the diffusion coefficient. The 1-Wasserstein distance between a QSD and the corresponding invariant probability measure can be quantitatively estimated. Some numerical results about both computation of QSDs and their sensitivity analysis are provided. [ABSTRACT FROM AUTHOR]

Cellulose aerogels were synthesized to be used for urea adsorption and targeting a fast adsorption rate and high adsorption capacity. This kind of urea adsorbent was synthesized by a sol–gel method in a simple NaOH/urea aqueous solution system. The aerogels were characterized by FT-IR spectroscopy, XRD, SEM, and N2 adsorption/desorption techniques and their adsorption properties were evaluated. The results showed that the aerogels comprised an ultralight mesoporous material with a large specific surface area and a porous three-dimensional network structure. The adsorption process followed the Freundlich model and the pseudo-first-order kinetic model. The synthesized aerogels had a superior adsorption capacity and a fast adsorption rate, and adsorption equilibrium could be reached within 60 min under the human physiological temperature. Therefore, this aerogel type of absorbent has potential applications for the adsorption of urea in dialysate. [ABSTRACT FROM AUTHOR]

Right ventricular (RV) function is one of the critical factors affecting the prognosis of fetuses with hypoplastic left heart syndrome (HLHS). Our study objectives included assessment of cardiac function and comprehensive measurement of cardiac microstructure. We retrospectively studied 42 fetuses diagnosed as HLHS by echocardiography. Myocardial deformation of the right ventricular wall was calculated automatically in offline software. Postmortem cardiac imaging for three control fetal hearts and four HLHS specimens was performed by a 9.4T DTI scanner. Myocardial deformation parameters of the RV (including strain, strain rate, and velocity) were significantly lower in HLHS fetuses (all p < 0.01). FA values increased (0.18 ± 0.01 vs. 0.21 ± 0.02; p < 0.01) in HLHS fetuses, but MD reduced (1.3 ± 0.15 vs. 0.88 ± 0.13; p < 0.001). The HLHS fetuses' RV lateral base wall (−7.31 ± 51.91 vs. −6.85 ± 31.34; p = 0.25), middle wall (1.71 ± 50.92 vs. −9.38 ± 28.18; p < 0.001), and apical wall (−6.19 ± 46.61 vs. −11.16 ± 29.86, p < 0.001) had HA gradient ascent but HA gradient descent in the anteroseptal wall (p < 0.001) and inferoseptal wall (p < 0.001). RV basal lateral wall HA degrees were correlated with RVGLS (R2 = 0.97, p = 0.02). MD values were positively correlated with RVGLS (R2 = 0.93, p = 0.04). Our study found morphological and functional changes of the RV in HLHS fetuses, and cardiac function was related to the orientation patterns of myocardial fibers. It may provide insight into understanding the underlying mechanisms of impaired RV performance in HLHS. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides are widely acknowledged as an alternative class of antimicrobial agents. In this study, a lysine-rich scorpion peptide derivative Pacavin-5K was designed, which showed an improved antibacterial spectrum, significantly higher antibacterial activity, and lower toxicity compared to the native peptide. It also showed an improved thermal and serum stability. Notably, Pacavin-5K significantly decreased the bacterial counts in the wounded region in the mouse cutaneous infection model caused by Staphylococcus aureus and Pseudomonas aeruginosa. Moreover, Pacavin-5K did not induce bacterial resistance associated with its antibacterial mechanism disrupting the membrane. Furthermore, Pacavin-5K could kill the S. aureus cells at the biofilm state. Overall, Pacavin-5K could be a potential alternative antibacterial agent against skin infection caused by S. aureus and P. aeruginosa. [Display omitted] • Pacavin-5K showed excellent antibacterial activity in vitro and in vivo. • Pacavin-5K showed excellent thermal and serum stability. • Pacavin-5K killed bacterial cells mainly by disrupting the membrane. • Pacavin-5K did not induce bacterial resistance. • Pacavin-5K could be a potent anti-infective agent against skin infection. [ABSTRACT FROM AUTHOR]

The gastropod mollusk Limax flavus , one of the most widespread pests in China, is used to treat infectious diseases in traditional Chinese medicine. However, little genomic information is available for this non-model species. In this study, the whole-body transcriptome of L. flavus was sequenced using next generation sequencing technology. A total of 6.81 Gb clean reads were obtained, which were assembled into 150,766 transcripts with 132,206 annotated unigenes. Functionally classification assigned 30,542 unigenes to 56 Gene Ontology terms, 16,745 unigenes were divided into 26 euKaryotic Ortholog Groups of proteins categories, and 13,854 unigenes were assigned to 230 Kyoto Encyclopedia of Genes and Genomes pathways. Furthermore, we identified 17,251 simple sequence repeats and several kinds of antimicrobial peptide and protein (AMPs) genes. The transcriptome data of L. flavus will provide a valuable genomic resource for further studies on this species, and the AMPs identified in L. flavus will support its medical potential. • The gastropod mollusk Limax flavus is used to treat infectious diseases in traditional Chinese medicine. • Little genomic information is available for the non-model species L. flavus. • This study is the first whole transcriptome analysis of L. flavus. • It will help explore the genome of L. flavus and promote the medicinal use of L. flavus. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides have recently become extremely popular as a novel class of antimicrobial agents. AMP MK049518 (FLGLLGSVLGSVLPSIFK), identified from the crab-scorpion Didymocentrus krausi , only possesses significant antibacterial activity against Gram-positive bacteria. In this study, a derivative G2K–S3K was designed with an excellent antibacterial spectrum and significantly higher antibacterial activity compared to the natural peptide. G2K–S3K also demonstrated excellent serum- and thermal-stability and did not induce bacterial resistance. In the Staphylococcus aureus and Pseudomonas aeruginosa -induced skin infection in mice, G2K–S3K significantly decreased bacterial counts in the wound by topical application. Thus, G2K–S3K could be a potent topical anti-infective agent against the skin infection caused by S. aureus and P. aeruginosa. • Scorpion venoms have been good resources for the discovery of antimicrobial peptides. • A scorpion-derived peptide, G2K–S3K, with improved antibacterial spectrum and activity was designed in this study. • G2K–S3K showed excellent serum- and thermal-stability and did not induce bacterial resistance. • G2K–S3K could significantly decrease the counts of Staphylococcus aureus and Pseudomonas aeruginosa in the wounded region. • G2K–S3K could be a potent topical anti-infective agent against skin infection. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) are not only involved in individual growth and metabolism, but they are also associated with inflammation and homeostasis of articular cartilage and bone. Recent studies have identified the involvement of IGF-1 and IGFBP-3 in the development of rheumatoid arthritis (RA). Nevertheless, the results were inconsistent, and the relevant data were not synthetically assessed. Therefore, this review aimed to systematically evaluate the associations of serum IGF-1 and IGFBP-3 levels with the development of RA. Several databases were used to retrieve relevant publications (up to January 2018). Pooled standard mean difference (SMD) and 95% confidence interval (CI) were demonstrated using a forest plot. A total of 27 studies from 19 publications were included. Meta-analysis results showed that RA patients had lower serum IGF-1 levels when compared to controls (SMD = −0.650, 95% CI = −1.184 to −0.115, P =.017). However, there was no significant association between serum IGFBP-3 levels and RA (SMD = 0.590, 95% CI = −1.323 to 2.504, P =.545). Subgroup analyses further showed that serum IGF-1 levels in RA patients are discrepant in terms of race, age, and measurement type (all P <.05). In conclusion, the decreased levels of serum IGF-1 were closely associated with the development of RA. Future longitudinal studies are needed to validate the link between serum IGF-1 levels with RA pathogenesis as well as the effects of IGF-1 on RA treatment. [ABSTRACT FROM AUTHOR]

Previous studies found that the interleukin (IL)-17 level was elevated in inflammatory arthritis, but results were inconsistent. This meta-analysis aimed to investigate the association of IL-17 cytokine with osteoarthritis (OA), rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Relevant studies were searched using databases. Standardized mean difference (SMD) was calculated. Correlation coefficient was utilized to evaluate the relationship between IL-17 and disease activity of AS and RA. Subgroup analysis, sensitivity analysis and meta-regression were applied to explore the sources of heterogeneity. 83 records were enrolled. The IL-17 level was elevated in AS (SMD = 2.348, P <.001), RA (SMD = 1.502, P <.001), PsA (SMD = 1.710, P <.001) and OA (SMD = 1.192, P =.016), and similar results occurred in subgroup analysis. Furthermore, the IL-17 level was positively associated with disease activity of AS and RA. Circulating IL-17 level is significantly elevated in inflammatory arthritis and is related to the disease activity of AS and RA, suggesting that it plays an important role in the pathogenesis and progression of inflammatory arthritis (especially in AS and RA). • IL-17 was elevated in Asians and Caucasians AS and RA patients. • IL-17 was elevated in large and small sample size for AS, RA and PsA patients. • IL-17 level was correlated with disease activity in AS and RA patients. [ABSTRACT FROM AUTHOR]

A fluorinated aza-BODIPY derivative BDPF was developed as a small molecule contrast agent, which displayed highly efficient near infrared fluorescence/photoacoustic/19F MR tri-modality tumor imaging. [ABSTRACT FROM AUTHOR]

Abstract Objective This study aimed to assess the association between two tag single nucleotide polymorphisms (SNPs) (rs68177277 and rs11624293) of G protein-coupled receptor 65 (GPR65) gene and ankylosing spondylitis (AS) susceptibility in a Chinese Han population. Methods 673 patients with AS diagnosed according to the modified New York criteria and 679 age- and gender-matched healthy controls were recruited. SNP genotyping for rs68177277 and rs11624293 polymorphisms were performed using the SNPscan technique. Disease activity was assessed by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). Results Genotype and allele distribution of rs11624293 but not rs68177277 were significantly different between AS and controls (p = 0.004 and p = 0.002). Compared to the wild-type T/T genotype and T allele at rs11624293, the frequencies of C/T genotype and C allele were significantly higher in AS than controls after adjusting for age and gender (OR = 1.527, 95%CIs: 1.190–1.958; OR = 1.515, 95%CIs: 1.183–1.942, respectively). Dominant and co-dominant model of rs11624293 were predictive of AS susceptibility. In AS patients, the genotype of rs11624293 was significantly associated with BASFI scores in those with low disease activity (BASDAI < 4, p = 0.007). Conclusions The results of our study suggest that rs11624293 polymorphism of GPR65 gene is associated with the susceptibility and severity of AS in Chinese Han population. [ABSTRACT FROM AUTHOR]

Tracking drugs with 19F MRI would be beneficial for developing theranostics and optimizing drug therapy. To this end, a fluorinated dendritic amphiphile with high 19F MRI sensitivity and biocompatibility has been developed for 19F MRI tracking of doxorubicin (DOX)-loaded liposomes in mice, which may provide an effective platform to in vivo trace various drugs with 19F MRI. [ABSTRACT FROM AUTHOR]

Chronic obstructive pulmonary disease (COPD) is regarded as a persistent respiratory symptom, mainly caused by cigarette smoking. Recent data have suggested that some miRNAs are involved in the pathogenesis of COPD. Here, we found that miR-195 was significantly upregulated in the lung tissues of patients with COPD compared to in never smokers. miR-195 expression was also upregulated in cigarette smoke (CS)-exposed mice. Lentivirus-mediated knockdown of miR-195 alleviated CS-induced lung pathological changes and reduced inflammatory cell infiltration as well as production of interleukin-6 and tumor necrosis factor-α in bronchoalveolar lavage fluid. Mechanically, a positive correlation was found between miR-195 and phosphorylation of Akt in lung tissues of COPD patients. PHLPP2 was confirmed as a direct downstream target of miR-195 and negative regulator of miR-195 expression. Inhibition of PHLPP2 enhanced Akt phosphorylation and increased interleukin-6 and tumor necrosis factor-α production in BEAS-2B cells, resembling the effects of miR-195 overexpression. Collectively, our data indicate that miR-195 has a pathogenetic role in CS-induced COPD and regulates Akt signaling by suppressing PHLPP2 expression. miR-195 may be an effective therapeutic target in COPD. [ABSTRACT FROM AUTHOR]

Monitoring a drug-delivery system with an imaging modality is of great importance for detailed understanding of drug-delivery processes and for achieving optimal therapeutic effects. Here, novel fluorinated self-assembled dendrimers with a single 19F NMR signal were conveniently synthesized on multigram scales, and 19F magnetic resonance, including spectroscopy (19F NMR) and imaging (19F MRI), was used to monitor the fluorinated dendrimer-based self-assembled drug-delivery systems. It was found that 19F NMR and 19F MRI were convenient and sensitive tools to monitor the self-assembly and drugloading processes and to detect weak interactions between the drug and the drug-delivery vehicle because changes in the selfassembly profile sensitively induced corresponding 19F magnetic resonance responses. [ABSTRACT FROM AUTHOR]

A new magnetic resonance imaging (MRI) molecular sensor for hydrogen sulfide detection and imaging using the nuclear spin resonance of hyperpolarized 129Xe is developed. The designed MRI sensor employs cryptophane for NMR sensing, together with an azide group serving as a reaction site. It demonstrates a 'proof-of-concept' that a fluorescent H2S probe can be linked to a xenon-binding cryptophane and thereby converted into an MRI probe, which could provide a very generalizable template. [ABSTRACT FROM AUTHOR]

For h-periodic coefficients and any integer k>2 it is well known that the eigenvalues of some self-adjoint complex boundary condition on the interval [ a , a + h ] are the same as the periodic eigenvalues on the interval [ a , a + kh ] . For each k we identify explicitly which of the uncountable number of complex conditions generates these periodic eigenvalues. In addition, we prove an analogous result for semi-periodic eigenvalues. [ABSTRACT FROM AUTHOR]

The emergence of antibiotic resistance has severely impaired the treatment of infections caused by Pseudomonas aeruginosa. There are few studies related to comparing the antibiotics resistance mechanisms of P. aeruginosa against different antibiotics. In this study, RNA sequencing was used to investigate the differences of transcriptome between wild strain and four antibiotics resistant strains of P. aeruginosa PAO1 (polymyxin B, ciprofloxacin, doxycycline, and ceftriaxone). Compared to the wild strain, 1907, 495, 2402, and 116 differentially expressed genes (DEGs) were identified in polymyxin B, ciprofloxacin, doxycycline, and ceftriaxone resistant PAO1, respectively. After analysis of genes related to antimicrobial resistance, we found genes implicated in biofilm formation (pelB , pelC , pelD , pelE , pelF , pelG , algA , algF , and alg44) were significantly upregulated in polymyxin B-resistant PAO1, efflux pump genes (mexA , mexB , oprM) and biofilm formation genes (pslJ , pslK and pslN) were upregulated in ciprofloxacin-resistant PAO1; other efflux pump genes (mexC , mexD , oprJ) were upregulated in doxycycline-resistant PAO1; ampC were upregulated in ceftriaxone-resistant PAO1. As a consequence of antibiotic resistance, genes related to virulence factors such as type Ⅱ secretion system (l asA , lasB and piv) were significantly upregulated in polymyxin B-resistant PAO1, and type Ⅲ secretion system (exoS , exoT , exoY , exsA , exsB , exsC , exsD , pcrV , popB , popD , pscC , pscE , pscG , and pscJ) were upregulated in doxycycline-resistant PAO1. While, ampC were upregulated in ceftriaxone-resistant PAO1. In addition, variants were obtained in wild type and four antibiotics resistant PAO1. Our findings provide a comparative transcriptome analysis of antibiotic resistant mutants selected by different antibiotics, and might assist in identifying potential therapeutic strategies for P. aeruginosa infection. • Upregulated pelB-G , algA , algF and alg44 might result in polymyxin B resistance to PAO1. • Enhanced expression of mexA , mexB and oprM might contribute to ciprofloxacin resistance to PAO1. • Upregulated mexC , mexD , oprJ and T3SS genes might lead to resistance and increased virulence in doxycycline resistant PAO1. • The ceftriaxone resistance to PAO1 might be due to upregulated ampC. [ABSTRACT FROM AUTHOR]

Objectives To compare the performance of the multiparametric magnetic resonance imaging (mpMRI) radiomics and 18F-Prostate-specific membrane antigen (PSMA)-1007 PET/CT radiomics model in diagnosing extracapsular extension (EPE) in prostate cancer (PCa), and to evaluate the performance of a multimodal radiomics model combining mpMRI and PET/CT in predicting EPE. Methods We included 197 patients with PCa who underwent preoperative mpMRI and PET/CT before surgery. mpMRI and PET/CT images were segmented to delineate the regions of interest and extract radiomics features. PET/CT, mpMRI, and multimodal radiomics models were constructed based on maximum correlation, minimum redundancy, and logistic regression analyses. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC) and indices derived from the confusion matrix. Results AUC values for the mpMRI, PET/CT, and multimodal radiomics models were 0.85 (95% CI, 0.78-0.90), 0.73 (0.64-0.80), and 0.83 (0.75-0.89), respectively, in the training cohort and 0.74 (0.61-0.85), 0.62 (0.48-0.74), and 0.77 (0.64-0.87), respectively, in the testing cohort. The net reclassification improvement demonstrated that the mpMRI radiomics model outperformed the PET/CT one in predicting EPE, with better clinical benefits. The multimodal radiomics model performed better than the single PET/CT radiomics model (P  <  .05). Conclusion The mpMRI and 18F-PSMA-PET/CT combination enhanced the predictive power of EPE in patients with PCa. The multimodal radiomics model will become a reliable and robust tool to assist urologists and radiologists in making preoperative decisions. Advances in knowledge This study presents the first application of multimodal radiomics based on PET/CT and MRI for predicting EPE. [ABSTRACT FROM AUTHOR]

Background: The difficulty of early diagnosis of bloodstream infection in the elderly patients leads to high mortality. Therefore, it is essential to determine some new methods of early warning of bloodstream infection in the elderly patients for timely adjustment of treatment and improvement of prognosis. Methods: Patients aged over 65 years with suspected bloodstream infections were included and divided into bloodstream infection (BSI) and non-bloodstream infection (non-BSI) groups based on blood culture results. The morphology of microparticles (MPs) was observed by using transmission electron microscopy, and the number of MPs was dynamically monitored by flow cytometry. Results: A total of 140 patients were included in the study: 54 in the BSI group and 86 in the non-BSI group. Total MPs (T-MPs) ≥ 6000 events/µL (OR, 7.693; 95% CI 2.944–20.103, P < 0.0001), neutrophil-derived MPs (NMPs) ≥ 500 events/µL (OR, 12.049; 95% CI 3.574–40.623, P < 0.0001), and monocyte counts ≤ 0.4 × 109/L (OR, 3.637; 95% CI 1.415–9.348, P = 0.007) within 6 h of fever were independently associated with bloodstream infection in the elderly patients. We also developed an early warning model for bloodstream infection in the elderly patients with an area under the curve of 0.884 (95% CI 0.826–0.942, P < 0.0001), sensitivity of 86.8%, specificity of 76.5%, positive predictive value of 70.8%, and negative predictive value of 89.8%. Conclusion: The early warning model of bloodstream infection based on circulating T-MPs, NMPs, and monocyte counts within 6 h of fever in the elderly patients was helpful in early detection of bloodstream infection and therefore promptly adjustment of treatment plan. [ABSTRACT FROM AUTHOR]

Background: The rational design of theranostic nanoprobe to present responsive effect of therapeutic potency and enhanced diagnostic imaging in tumor milieu plays a vital role for efficient personalized cancer therapy and other biomedical applications. We aimed to afford a potential strategy to pose both T1- and T2-weighted MRI functions, and thereby realizing imaging guided drug delivery and targeted therapy. Results: Theranostic nanocomposites Mn-porphyrin&Fe3O4@SiO2@PAA-cRGD were fabricated and characterized, and the nanocomposites were effectively used in T1- and T2-weighted MRI and pH-responsive drug release. Fluorescent imaging also showed that the nanocomposites specifically accumulated in lung cancer cells by a receptor-mediated process, and were nontoxic to normal cells. The r2/r1 ratio was 20.6 in neutral pH 7.4, which decreased to 7.7 in acidic pH 5.0, suggesting the NCs could act as an ideal T1/T2 dual-mode contrast agent at acidic environments of tumor. For in vivo MRI, T1 and T2 relaxation was significantly accelerated to 55 and 37%, respectively, in the tumor after i.v. injection of nanocomposites. Conclusion: The synthesized nanocomposites exhibited highly sensitive MRI contrast function no matter in solution, cells or in vivo by synergistically enhancing positive and negative magnetic resonance imaging signals. The nanocomposites showed great potential for integrating imaging diagnosis and drug controlled release into one composition and providing real-time imaging with greatly enhanced diagnostic accuracy during targeted therapy. [ABSTRACT FROM AUTHOR]

Hyperpolarization is one of the methods for NMR signal enhancement. NMR sensitivity can be further enhanced by combining hyperpolarization with chemical exchange saturation transfer (CEST), which termed “Hyper‐CEST”. A H2S sensor is reported that contains a cryptophane group for NMR sensing and a naphthalimide group for fluorescence sensing, together with an azide group as the reaction site. Upon reacting with H2S, the fluorescence and 129Xe NMR signal changes, which may provide a universal template for converting a fluorescence sensor into an 129Xe Hyper‐CEST MRI sensor. More information can be found in the Communication by X. Zhou, M. Liu, et al. on page 7648. [ABSTRACT FROM AUTHOR]

Waste toner with high carbon content has the potential to become a carbon material, but its utilization is limited due to the low carbonization yield. In this work, a carbon-based solid acid was prepared by carbonization and sulfonation of waste toner with the aid of sulfuric acid. The characterization of its structure and the evaluation of its properties revealed that sulfuric acid played three roles in the process of carbon-based solid acid prepared from waste toner (WT-CSA). Specifically, this method not only solved the problem of low yield of carbon precursor (CP) obtained by carbonization of waste toner but also introduced thiophene sulfur into the aromatic carbon flakes during the carbonization process. Moreover, thiophene sulfur makes the sulfonation easier, thus increasing the density of –SO3H. In addition, the activity and cyclic stability of the catalyst were evaluated by cellulose hydrolysis. The results show that the catalyst exhibits excellent hydrolytic activity and hydrothermal stability. [ABSTRACT FROM AUTHOR]

Maize is a major crop essential for food and feed, but its production is threatened by various biotic and abiotic stresses. Drought is one of the most common abiotic stresses, causing severe crop yield reduction. Although several studies have been devoted to selecting drought‐tolerant maize lines and detecting the drought‐responsive mechanism of maize, the transcriptomic differences between drought‐tolerant and drought‐susceptible maize lines are still largely unknown. In our study, RNA‐seq was performed on leaves of the drought‐tolerant line W9706 and the drought‐susceptible line B73 after drought treatment. We identified 3147 differentially expressed genes (DEGs) between these two lines. The upregulated DEGs in W9706 were enriched in specific processes, including ABA signaling, wax biosynthesis, CHO metabolism, signal transduction and brassinosteroid biosynthesis‐related processes, while the downregulated DEGs were enriched in specific processes, such as stomatal movement. Altogether, transcriptomic analysis suggests that the different drought resistances were correlated with the differential expression of genes, while the drought tolerance of W9706 is due to the more rapid response to stimulus, higher water retention capacity and stable cellular environment under water deficit conditions. [ABSTRACT FROM AUTHOR]

Nitroreductase (NTR) is an important biomarker widely used to evaluate the degree of tumor hypoxia. Although a few optical methods have been reported for detecting nitroreductase at low concentration ranges, an effective strategy for nitroreductase monitoring in vivo without limits to the imaging depth is still lacking. Herein, a novel dual‐mode NIR fluorescence and 19F MRI agent, FCy7‐NO2, is proposed for imaging tumor hypoxia. We show that FCy7‐NO2 serves as not only a rapid NIR fluorescence enhanced probe for monitoring and bioimaging of nitroreductase in tumors, but also a novel 19F MR chemical shift‐sensitive contrast agent for selectively detecting nitroreductase catalyzed reduction. Notably, integrating two complementary imaging technologies into FCy7‐NO2 enables sensitive detection of nitroreductase in a broad concentration range without tissue‐depth limit. In general, this agent has a remarkable response to nitroreductase, which provides a promising method for understanding tumor evolution and its physiological role in the hypoxic microenvironment. [ABSTRACT FROM AUTHOR]

Nitroreductase (NTR) is an important biomarker widely used to evaluate the degree of tumor hypoxia. Although a few optical methods have been reported for detecting nitroreductase at low concentration ranges, an effective strategy for nitroreductase monitoring in vivo without limits to the imaging depth is still lacking. Herein, a novel dual‐mode NIR fluorescence and 19F MRI agent, FCy7‐NO2, is proposed for imaging tumor hypoxia. We show that FCy7‐NO2 serves as not only a rapid NIR fluorescence enhanced probe for monitoring and bioimaging of nitroreductase in tumors, but also a novel 19F MR chemical shift‐sensitive contrast agent for selectively detecting nitroreductase catalyzed reduction. Notably, integrating two complementary imaging technologies into FCy7‐NO2 enables sensitive detection of nitroreductase in a broad concentration range without tissue‐depth limit. In general, this agent has a remarkable response to nitroreductase, which provides a promising method for understanding tumor evolution and its physiological role in the hypoxic microenvironment. [ABSTRACT FROM AUTHOR]

How likely genetic variations associated with environment identified in silico from genome wide association study are functionally relevant to environmental adaptation has been largely unexplored experimentally. Here we analyzed top 29 genes containing polymorphisms associated with local temperature variation (minimum, mean, maximum) among 1129 natural accessions of Arabidopsis thaliana. Their loss‐of‐function mutants were assessed for growth and stress tolerance at five temperatures. Twenty genes were found to affect growth or tolerance at one or more of these temperatures. Significantly, genes associated with maximum temperature more likely have a detect a function at higher temperature, while genes associated with minimum temperature more likely have a function at lower temperature. In addition, gene variants are distributed more frequently at geographic locations where they apparently offer an enhanced growth or tolerance for five genes tested. Furthermore, variations in a large proportion of the in silico identified genes associated with minimum or mean‐temperatures exhibited a significant association with growth phenotypes experimentally assessed at low temperature for a small set of natural accessions. This study shows a functional relevance of gene variants associated with environmental variables and supports the feasibility of the use of local temperature factors in investigating the genetic basis of temperature adaptation. SUMMARY STATEMENT: Whether or not genetic variations associated with local environmental variables are functionally relevant to environmental adaptation have not been experimentally investigated. Here we analyzed top genes with polymorphisms associated with three temperature variables of 1129 natural accessions of Arabidopsis thaliana and showed a functional relevance of these genes in temperature responses, supporting the feasibility of using in silico environment association to investigate environmental adaptation. [ABSTRACT FROM AUTHOR]

Antimicrobial peptides (AMPs) have started to garner more interest as novel antimicrobial agents. The scorpion venom peptide ctry2459 was modified to CT-K3K7 by lysine substitutions at the 3rd and 7th positions to increase the cationic properties. We discovered that the modified peptides CT-K3K7 had improved antibacterial activity, higher thermal stability, as well as lower hemolytic activity. It can kill S. aureus and P. aeruginosa rapidly, and reduce the production of biofilm and live bacterial residues in biofilm in vitro. CT-K3K7 has also been demonstrated to decrease bacterial counts, abscess area, and inflammatory cell infiltration in the mouse subcutaneous abscess models that were duplicated by S. aureus and P. aeruginosa. CT-K3K7 has difficulty in inducing S. aureus and P. aeruginosa to develop drug resistance, which may be related to the bactericidal properties. CT-K3K7 increases cationic properties by lysine substitutions can increase the electrostatic force between the peptides and the bacterial surface, which can lead to an increase in bacterial membrane permeability and DNA binding. In conclusion, the modified peptide CT-K3K7 enhances the antimicrobial activity and can be a novel antimicrobial agent candidate for the treatment of infections by S. aureus and P. aeruginosa. [Display omitted] • The peptide CT-K3K7, modified by a lysine substitution had a stronger bactericidal effect. • CT-K3K7 could eliminate Staphylococcus aureus and Pseudomonas aeruginosa in vitro, and reduce the production of biofilm. • CT-K3K7 has been proven to have a bactericidal effect on the subcutaneous abscess model in mice. • The bactericidal mechanism of CT-K3K7 can destroy bacterial membranes and bind to the DNA through electrostatic force. [ABSTRACT FROM AUTHOR]

Background: Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue (PPAT). Accordingly, we aimed to construct a dynamic online nomogram to predict tumor short-term prognosis based on 18F-PSMA-1007 PET/CT of PPAT.Data from 268 prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT before prostatectomy were analyzed retrospectively for model construction and validation (training cohort: n = 156; internal validation cohort: n = 65; external validation cohort: n = 47). Radiomics features (RFs) from PET and CT were extracted. Then, the Rad-score was constructed using logistic regression analysis based on the 25 optimal RFs selected through maximal relevance and minimal redundancy, as well as the least absolute shrinkage and selection operator. A nomogram was constructed to predict short-term prognosis which determined by persistent PSA.The Rad-score consisting of 25 RFs showed good discrimination for classifying persistent PSA in all cohorts (all P < 0.05). Based on the logistic analysis, the radiomics-clinical combined model, which contained the optimal RFs and the predictive clinical variables, demonstrated optimal performance at an AUC of 0.85 (95% CI: 0.78—0.91), 0.77 (95% CI: 0.62—0.91) and 0.84 (95% CI: 0.70—0.93) in the training, internal validation and external validation cohorts. In all cohorts, the calibration curve was well-calibrated. Analysis of decision curves revealed greater clinical utility for the radiomics-clinical combined nomogram.The radiomics-clinical combined nomogram serves as a novel tool for preoperative individualized prediction of short-term prognosis among PCa patients.Methods: Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue (PPAT). Accordingly, we aimed to construct a dynamic online nomogram to predict tumor short-term prognosis based on 18F-PSMA-1007 PET/CT of PPAT.Data from 268 prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT before prostatectomy were analyzed retrospectively for model construction and validation (training cohort: n = 156; internal validation cohort: n = 65; external validation cohort: n = 47). Radiomics features (RFs) from PET and CT were extracted. Then, the Rad-score was constructed using logistic regression analysis based on the 25 optimal RFs selected through maximal relevance and minimal redundancy, as well as the least absolute shrinkage and selection operator. A nomogram was constructed to predict short-term prognosis which determined by persistent PSA.The Rad-score consisting of 25 RFs showed good discrimination for classifying persistent PSA in all cohorts (all P < 0.05). Based on the logistic analysis, the radiomics-clinical combined model, which contained the optimal RFs and the predictive clinical variables, demonstrated optimal performance at an AUC of 0.85 (95% CI: 0.78—0.91), 0.77 (95% CI: 0.62—0.91) and 0.84 (95% CI: 0.70—0.93) in the training, internal validation and external validation cohorts. In all cohorts, the calibration curve was well-calibrated. Analysis of decision curves revealed greater clinical utility for the radiomics-clinical combined nomogram.The radiomics-clinical combined nomogram serves as a novel tool for preoperative individualized prediction of short-term prognosis among PCa patients.Results: Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue (PPAT). Accordingly, we aimed to construct a dynamic online nomogram to predict tumor short-term prognosis based on 18F-PSMA-1007 PET/CT of PPAT.Data from 268 prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT before prostatectomy were analyzed retrospectively for model construction and validation (training cohort: n = 156; internal validation cohort: n = 65; external validation cohort: n = 47). Radiomics features (RFs) from PET and CT were extracted. Then, the Rad-score was constructed using logistic regression analysis based on the 25 optimal RFs selected through maximal relevance and minimal redundancy, as well as the least absolute shrinkage and selection operator. A nomogram was constructed to predict short-term prognosis which determined by persistent PSA.The Rad-score consisting of 25 RFs showed good discrimination for classifying persistent PSA in all cohorts (all P < 0.05). Based on the logistic analysis, the radiomics-clinical combined model, which contained the optimal RFs and the predictive clinical variables, demonstrated optimal performance at an AUC of 0.85 (95% CI: 0.78—0.91), 0.77 (95% CI: 0.62—0.91) and 0.84 (95% CI: 0.70—0.93) in the training, internal validation and external validation cohorts. In all cohorts, the calibration curve was well-calibrated. Analysis of decision curves revealed greater clinical utility for the radiomics-clinical combined nomogram.The radiomics-clinical combined nomogram serves as a novel tool for preoperative individualized prediction of short-term prognosis among PCa patients.Conclusion: Rising prostate-specific antigen (PSA) levels following radical prostatectomy are indicative of a poor prognosis, which may associate with periprostatic adipose tissue (PPAT). Accordingly, we aimed to construct a dynamic online nomogram to predict tumor short-term prognosis based on 18F-PSMA-1007 PET/CT of PPAT.Data from 268 prostate cancer (PCa) patients who underwent 18F-PSMA-1007 PET/CT before prostatectomy were analyzed retrospectively for model construction and validation (training cohort: n = 156; internal validation cohort: n = 65; external validation cohort: n = 47). Radiomics features (RFs) from PET and CT were extracted. Then, the Rad-score was constructed using logistic regression analysis based on the 25 optimal RFs selected through maximal relevance and minimal redundancy, as well as the least absolute shrinkage and selection operator. A nomogram was constructed to predict short-term prognosis which determined by persistent PSA.The Rad-score consisting of 25 RFs showed good discrimination for classifying persistent PSA in all cohorts (all P < 0.05). Based on the logistic analysis, the radiomics-clinical combined model, which contained the optimal RFs and the predictive clinical variables, demonstrated optimal performance at an AUC of 0.85 (95% CI: 0.78—0.91), 0.77 (95% CI: 0.62—0.91) and 0.84 (95% CI: 0.70—0.93) in the training, internal validation and external validation cohorts. In all cohorts, the calibration curve was well-calibrated. Analysis of decision curves revealed greater clinical utility for the radiomics-clinical combined nomogram.The radiomics-clinical combined nomogram serves as a novel tool for preoperative individualized prediction of short-term prognosis among PCa patients. [ABSTRACT FROM AUTHOR]

Microbial-catalyzed reductive dechlorination of polychlorinated biphenyls (PCBs) is largely affected by the indigenous sediment geochemical properties. In this study, the effects of nitrate on PCB dechlorination and microbial community structures were first investigated in Taihu Lake sediment microcosms. And biostimulation study was attempted supplementing acetate/lactate. PCB dechlorination was apparently inhibited under nitrate-reducing conditions. Lower PCB dechlorination rate and less PCB dechlorination extent were observed in nitrate amended sediment microcosms (T-N) than those in non-nitrate amended microcosms (T-1) during 66 weeks of incubation. The total PCB mass reduction in T-N was 17.6% lower than that in T-1. The flanked- para dechlorination was completely inhibited, while the ortho -flanked meta dechlorination was only partially inhibited in T-N. The 7.5 mM of acetate/lactate supplementation recovered PCB dechlorination by resuming ortho -flanked meta dechlorination. Repeated additions of lactate showed more effective biostimulation than acetate. Phylum Chloroflexi , containing most known PCB dechlorinators, was found to play a vital role on stability of the network structures. In T-N, putative dechlorinating Chloroflexi , Dehalococcoides and RDase genes rdh 12, pcb A4, pcb A5 all declined. With acetate/lactate supplementation, Dehalococcoides grew by 1–2 orders of magnitude and rdh 12, pcb A4, pcb A5 increased by 1–3 orders of magnitude. At Week 66, parent PCBs declined by 86.4% and 80.9% respectively in T-N-LA and T-N-AC compared to 69.9% in T-N. These findings provide insights into acetate/lactate biostimulation as a cost-effective approach for treating PCB contaminated sediments undergoing nitrate inhibition. [Display omitted] • PCB dechlorination was partially inhibited by nitrate. • The inhibition targeted flanked- para and ortho -flanked meta chlorines. • Both acetate and lactate triggered ortho and ortho -flanked meta dechlorination. • Acetate and lactate led to diverged microbial community but both induced RDase genes. • Lactate exhibited more efficient dechlorination stimulation than acetate. [ABSTRACT FROM AUTHOR]

Chilling is a major stress to plants of subtropical and tropical origins, including maize (Zea mays L.). To reveal the molecular mechanisms underlying chilling tolerance and survival in maize, we investigated transcriptomic responses to chilling stress in differentiated leaves and roots as well as in crowns with meristem activity. The application of chilling stress to shoots or roots each contributed to seedling lethality in maize. Comparison of maize lines with different chilling tolerance capacities revealed that chilling survival is highly associated with the up-regulation of abscisic acid biosynthesis and responses as well as transcriptional regulators in leaves and crowns. It was also associated with the down-regulation of translation in leaves and the heat response in crowns. Chilling treatment of all or part of the plants revealed that the response to distal chilling is very distinct from, and sometimes opposite to, the response to local or whole-plant chilling in both leaves and roots, suggesting communication between shoots and roots in the environmental response. This study thus provides information on transcriptomic responses in leaves, roots, and crowns under different chilling stresses in maize, and reveals potential chilling tolerance and survival mechanisms, which lay the ground for improving chilling tolerance in crop plants. [ABSTRACT FROM AUTHOR]

Glutamate dehydrogenase (GDH) is an important enzyme in ammonium metabolism, the activity of which is regulated by multiple factors. In this study, we investigate the effects of ammonium and potassium on the activity of maize GDH. Our results show that both ammonium and potassium play multiple roles in regulating the activity of maize GDH, with the specific roles depending on the concentration of potassium. Together with the structural information of GDH, we propose models for the substrate inhibition of ammonium, and the elimination of substrate inhibition by potassium. These models are supported by the analysis of statistic thermodynamics. We also analyze the binding sites of ammonium and potassium on maize GDH, and the conformational changes of maize GDH. The findings provide insight into the regulation of maize GDH activity by ammonium and potassium and reveal the importance of the dose and ratio of nitrogen and potassium in crop cultivation. [ABSTRACT FROM AUTHOR]

[Display omitted] • A mild method was developed to prepare the amine-functionalized cellulose aerogel. • The aerogel retains large specific surface area and low crystallinity. • Excessive graft density hinders urea adsorption. • Grafted amino or silicone hydroxy groups significantly promote urea adsorption. The development of efficient adsorbent materials to remove urea from dialysate is an effective way to solve the bottleneck limiting the development of a wearable artificial kidney. Three methods were used to fabricate amine-functionalized cellulose aerogels aiming to screen for excellent structures favorable for urea adsorption. The influence of APTES addition on the structure and adsorption performance of the adsorption materials was investigated. The kinetics and thermodynamics of urea adsorption were evaluated, and adsorption mechanisms were also discussed. Results indicate that the material prepared by the gentle method was still able to maintain a large specific surface area, large pore volume and low crystallinity. Amine-functionalized cellulose aerogels retain the original hydroxyl adsorption sites, and the amino or silanol hydroxyl as new adsorption active sites are also introduced. Furthermore, proper APTES graft density plays a critical role in the urea adsorption. The equilibrium adsorption capacity of urea on HA-N-NCA-10 is increased by 156%. [ABSTRACT FROM AUTHOR]

Many susceptibility genes of inflammatory bowel disease (IBD) are associated with ankylosing spondylitis (AS). Fucosyltransferase 2 (FUT2) and FUT3 genes are related to IBD. This study aimed to investigate whether these genes correlated with the susceptibility to AS. Questionnaires of 673 patients with AS, and peripheral blood specimens of the patients and 687 healthy controls were collected. FUT2 and FUT3 genes were genotyped using the SNPscan method. Frequency differences of the genes at different levels, haplotypes, and interactions were analyzed. No frequency differences were found between the cases and the controls in all the genotypes and the alleles of rs1047781, rs1800028, rs1800030, and rs812936. For rs28362459, a significant difference in allele frequencies was observed in the total participants between the groups [χ2 = 7.515, Pcorrected = 0.030; adjusted odds ratio (ORadjusted)G/T = 0.782; 95% confidence interval (CI), 0.650–0.941]. The frequencies of haplotypes TT (rs812936–rs28362459) (χ2 = 5.663, Ppermutation = 0.039) and TG (rs812936–rs28362459) (χ2 = 7.456, Ppermutation = 0.013) in the total participants, and TG (rs812936–rs28362459) in the female subgroup (χ2 = 5.624, Ppermutation = 0.047) showed significant differences between the cases and the controls. No frequency differences at the phenotypic level were found. Two-factor interactions were observed between rs28362459-TG and age, rs28362459-TG and sex, rs28362459 and rs1047781, and the Lewis and secretor status. Rs28362459-G was related to some aggravated symptoms of AS (all Pcorrected < 0.05). These findings indicated that FUT3 polymorphisms were associated with human predisposition to AS at the allele and haplotype level. Rs28362459-G might decrease the susceptibility to AS, but aggravate relevant symptoms. [ABSTRACT FROM AUTHOR]

Objectives: To explore the genetic interaction between Wnt/β-catenin signalling pathway genes and ankylosing spondylitis (AS) in the Chinese population. Methods: Six single-nucleotide polymorphisms (SNPs) in DKK1, LRP5, LRP6, and SOST genes were genotyped in 673 AS patients and 687 healthy controls by using SNPs can Technic. Single marker genetic association analysis was performed. Haplotypes were constructed after linkage disequilibrium analysis; additive, multiplicative, and higher-order interactions were analysed. Results: The DKK1 gene rs1569198 polymorphism was significantly associated with AS susceptibility in females (χ2 = 4.55, p =.03), but the association disappeared after Bonferroni correction. Moreover, a haplotype (T-G) in the DKK1 gene showed a protective role in AS susceptibility in females (p =.04). Significant additive interactions were observed between DKK1: rs1896368 and LRP5: rs3736228, relative excess risk due to interaction (RERI) = 0.40, 95% CI = 0.08 – 0.71; attributable proportion due to interaction (AP) = 51%, 95% CI = 0.07 – 0.94, DKK1: rs1569198 and LRP5: rs3736228 (RERI = 0.49, 95% CI = 0.12 – 0.86; AP = 49%, 95% CI = 0.17 – 0.82), LRP5: rs3736228 and SOST: rs4792909 (RERI = 0.33, 95% CI = 0.002 – 0.65; AP = 41%, 95% CI = 0.01 – 0.81) in the dominant model. Conclusions: Our research implies a potential gene–gene interaction, thus revealing the importance of the Wnt/β-catenin signalling pathway for understanding the genetic architecture of AS. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of methylation levels of the IFN regulatory factor 8 (IRF8) gene promoter in the development of ankylosing spondylitis (AS). Methods: In this study, we compared the methylation levels of the IRF8 gene promoter between 99 AS patients and 99 healthy controls using MethylTarget approach. Quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) was performed to compare the mRNA levels of the IRF8 gene in the other 19 AS patients and 19 healthy controls. Results: Differential methylation was found in 91 CpG sites of the IRF8 gene promoter, and 4 CpG regions were highly methylated in AS patients compared to healthy controls (p < 0.05). In the verification stage, we found that the mRNA levels of the IRF8 gene in AS patients were significantly lower than that in controls (AS 0.77 (0.39–1.74), P = 0.038). Positive correlations between methylation of the IRF8 gene and the duration of disease, BASFI, and ESR were observed in AS patients. Conclusions: We found a significant hypermethylation of the IRF8 gene promoter and a downregulation of the mRNA levels of the IRF8 gene in AS patients. This suggests that aberrant methylation of the IRF8 gene promoter may probably contribute to the development and pathogenesis of AS through regulating the expression of mRNA. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the role of osteoprotegerin (OPG), receptor activator of nuclear factor-kB ligand (RANKL), and RANKL/OPG ratio in the pathogenesis of ankylosing spondylitis (AS). Methods: Studies that compared serum levels of OPG, RANKL, and RANKL/OPG ratio between AS patients and healthy controls were gathered. Pooled standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated by the random-effects model. Results: Twenty studies containing 1592 AS patients and 1064 healthy controls were included in this meta-analysis. Serum levels of OPG, RANKL, and RANKL/OPG ratio in AS patients were significantly higher than that in normal controls (OPG: SMD = 0.401, 95%CI = 0.026–0.777, p = 0.036; RANKL: SMD = 1.116, 95%CI = 0.510–1.723, p < 0.001; RANKL/OPG ratio: SMD = 0.691, 95%CI = 0.084–1.299, p = 0.026, respectively). Subgroup analysis suggested that Asian AS patients and patients with elevated ESR (ESR >20 mm/h) had higher serum OPG levels compared to normal controls. Asian patients, CRP >10 mg/L, ESR >20 mm/h, duration of disease ≤8 years, and BASDAI score >4 points subgroups showed increased RANKL levels compared to controls. Conclusions: Serum levels of OPG, RANKL, and RANKL/OPG ratio may be used as potential susceptible biomarkers for AS, but they could be influenced by race, inflammatory factors, and disease activity of AS patients. [ABSTRACT FROM AUTHOR]

Various studies have investigated the serum sclerostin and bone morphogenetic protein-2 (BMP-2) levels in patients with ankylosing spondylitis (AS), but the results were inconsistent. The aim of this meta-analysis was to synthetically assess the associations of serum levels of sclerostin and BMP-2 with AS. Multiple electronic databases were searched to locate relevant articles published before November 2018. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Totally, 21 studies were included. Meta-analysis results showed no significant difference between AS group and control group in serum sclerostin levels (SMD = 0.098, 95% CI - 0.395 to 0.591, p = 0.697). Nevertheless, serum BMP-2 levels in AS patients were higher than that in controls (SMD = 1.184, 95% CI 0.209 to 2.159, p = 0.017). Subgroup analysis demonstrated that European and South American AS patients had lower serum levels of sclerostin than controls. AS patients with age ≥ 40 years, erythrocyte sedimentation rate (ESR) ≤ 20 mm/h and Bath Ankylosing Spondylitis Functional Index (BASFI) < 4 had statistically significant lower serum sclerostin concentrations compared to controls. Chinese and Korean AS patients as well as patients with lower CRP had higher serum BMP-2 levels than controls, and country may be a source of heterogeneity across the studies. No publication bias existed and sensitivity analysis confirmed the stability of results. Serum BMP-2, but not sclerostin levels may be closely related to the development of AS. [ABSTRACT FROM AUTHOR]

Here, a novel method was developed for suppressing 129Xe signals in cucurbit[6]uril (CB6) until the trigger is activated by a specific enzyme. Due to its noncovalent interactions with amino-groups and CB6, putrescine dihydrochloride (Put) was chosen for blocking interactions between 129Xe and CB6. Upon adding diamine oxidase (DAO), Put was released from CB6 and a 129Xe@CB6 Hyper-CEST signal emerged. This proposed 129Xe biosensor was then tested in small intestinal villus epithelial cells. [ABSTRACT FROM AUTHOR]

As a promising cell tracking technology, 19F MRI suffers from low sensitivity. Here, fluorinated nanoemulsions with a unified 19F signal and paramagnetic relaxation enhancement were developed as 19F MRI cellular tracers with high stability, size controllability, biocompatibility, cellular uptake, and dual-modality for sensitive in vivo RAW264.7 cell tracking. [ABSTRACT FROM AUTHOR]

Background Current findings regarding serum Dickkopf-1 (DKK-1) concentration in ankylosing spondylitis (AS) have proven inconsistent. This meta-analysis was performed to provide a better understanding of serum DKK-1 and AS. Methods Online electronic databases were used to retrieve all relevant articles published before November 2017. The pooled standardized mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Results 23 studies, containing 1348 AS patients and 909 healthy controls, were included in this meta-analysis. No significant difference in serum DKK-1 concentration was found between AS patients and healthy controls (pooled SMD = 0.488, 95%CI = −0.176 to 1.152, p  = 0.150). Subgroup analyses suggested that serum DKK-1 in patients with increased C-reactive protein (CRP) (CRP > 10 mg/L) and high modified Stroke AS Spine Score (mSASSS) (mSASSS > 30) were significantly lower than healthy controls. Serum DKK-1 was, however, increased in patients with normal CRP (CRP   ≤ 10 mg/L). Conclusion Although serum DKK-1 concentration was not significantly different in AS vs. healthy controls, it may be used as a biomarker of inflammation and radiographic damage in AS. [ABSTRACT FROM AUTHOR]

Objective Dickkopf-1 (DKK-1) is an endogenous inhibitor of canonical Wnt pathway that was implicated in the pathogenesis of rheumatoid arthritis (RA), but the serum levels of DKK-1 in RA were inconsistent among studies. Therefore, we conducted a meta-analysis to systematically evaluate the relationship between serum DKK-1 levels and RA. Methods PubMed, Web of Science and Cochrane Library were comprehensively retrieved till 1 January 2018 for pertinent studies. The pooled standard mean differences (SMDs) of serum DKK-1 levels were calculated according to the random effects model. Results Nine original studies containing 1305 RA patients and 504 healthy controls were included in the meta-analysis. The pooled SMD of serum DKK-1 between RA patients and healthy controls was 0.79 (95% CI = 0.11 to 1.48, Z  = 2.28 and P  = 0.023), indicating a significantly higher serum level of DKK-1 in RA patients. Conclusion Serum level of DKK-1 is elevated in patients with RA compared to healthy controls, suggesting an important role of DKK-1 in the pathogenesis and treatment of RA. [ABSTRACT FROM AUTHOR]

To improve the druggability of salinomycin, a 20-epi-amino-20-deoxysalinomycin derivatives library was synthesized with high efficacy from which a few salinomycin derivatives with high potency and selectivity were identified through comprehensive cytotoxicity assay, including a fluorine-19 magnetic resonance sensitive tool molecule. Using a K-ras cellular model, salinomycin and its derivatives showed different molecular mode of action from literature reports. These results would be valuable for developing salinomycin-based cancer therapy. [ABSTRACT FROM AUTHOR]

Objectives Various studies have researched the serum levels of leptin, adiponectin and resistin in patients with ankylosing spondylitis (AS), but the results were inconclusive. The purpose of this study was to systematically evaluate the correlations between serum levels of these adipokines and AS. Methods Electronic databases were retrieved to search relevant publications. Pooled standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the random-effect model. Cochrane Q test and I 2 statistic were used to test heterogeneity. Subgroup analysis and meta-regression were applied to assess possible sources of heterogeneity. Results A total of sixteen articles were included. Meta-analysis results indicated no statistical differences between AS patients and normal controls in serum leptin and adiponectin levels (leptin, SMD = 0.829, 95% CI = − 0.116 to 1.774, p = 0.085; adiponectin, SMD = 0.460, 95% CI = − 0.004 to 0.924, p = 0.052). However, AS patients had higher serum resistin levels than controls (SMD = 1.413, 95% CI = 0.294 to 2.531, p = 0.013). Subgroup analyses suggested that Asian and African AS patients as well as patients aged < 40 years had higher serum leptin and resistin levels when compared to controls. Serum adiponectin levels were higher in AS patients compared to controls in subgroup of age ≥ 40, and serum resistin levels in subgroup of BMI ≥ 25. Measurement method was a source of heterogeneity for resistin. Publication bias was not observed and the robustness of study results was confirmed by sensitivity analysis. Conclusion Serum resistin, but not leptin or adiponectin levels may be closely associated with the development of AS. [ABSTRACT FROM AUTHOR]

IL-22 provides a new insight into the mechanisms of autoimmunity, and copy number variations (CNVs) are associated with autoimmune diseases. This study aims to explore the association of IL-22 gene CNVs with ankylosing spondylitis (AS) susceptibility. The copy numbers of IL-22 gene (2 fragments: IL-22_1, IL-22_2) were examined by AccuCopy™ methods in a cohort of 649 AS patients and 628 controls. Association of IL-22 CNVs and AS susceptibility was analyzed, and AS risk was estimated by Odds Ratio (ORs) and 95% confidence intervals (CIs), and the Benjamini-Hochberg method was applied to regulate the false discovery rate (FDR). We found one copy of IL-22 gene was significantly associated with AS [OR = 0.345, 95%CI (0.144, 0.827), P = 0.013, P FDR = 0.026] in the IL-22_2 fragment, and this association still exist after adjustment of age and sex [OR = 0.344, 95%CI (0.143, 0.825), P = 0.017, P FDR = 0.034]. In the stratification analysis by gender, the statistical difference was detected in males in the IL-22_2 fragment [OR = 0.306, 95%CI (0.121, 0.778), P = 0.009, P FDR = 0.018; adjusted OR = 0.306, 95%CI (0.120, 0.777), P = 0.013, P FDR = 0.026]. We suggest that IL-22 CNVs are associated with AS and that lower copy number might be a protective factor for AS, especially in male patients. [ABSTRACT FROM AUTHOR]

To date, transcriptome profile analysis of maize seedlings in response to cold stress have been well documented; however, changes in protein species abundance of maize seedlings in response to cold stress are still unknown. Herein, leaves from the maize inbred line W9816 (a cold-resistance genotype) were harvested at three-leaf stage, and were used to identify the differential abundance protein species (DAPS) between chilling stress (4 °C) and control conditions (25 °C). iTRAQ-based quantitative proteomic were used in this study. As a result, 173 DAPS were identified after chilling stress. Bioinformatic analysis showed that 159 DAPS were annotated in 38 Gene Ontology functional groups, 108 DAPS were classified into 20 clusters of orthologous groups of protein categories, 99 DAPS were enrichment in KEGG pathways. Antioxidants assays validated that the iTRAQ results were reliable. Based on functional analysis, we concluded that the adaptive response of maize seedlings to chilling stress might be related to alleviation of photodamage caused by the over-energized state of thylakoid membrane, more energy produced through glycolysis, increased abundance of stress-responsive protein species, and improvement in the overall ability to scavenge ROS. Posttranscriptional regulation and posttranslational modifications also play important roles for maize to adapt to chilling stress. Biological significance The major challenge for maize breeders is the complexity of the response to chilling stress. Although extensive researches have been focus on maize chilling stress using segregating populations, epigenetics, transcriptomics, molecular biology, however, the molecular mechanism of chilling stress in maize remains to be further elucidated. In the present paper, a differential proteomic analysis was performed and the results revealed the adaptive response of maize seedlings to chilling stress might be related to alleviation of photodamage caused by the over-energized state of thylakoid membrane, more energy produced through glycolysis, increased abundance of stress-responsive protein species, improvement in the overall ability to scavenge ROS, including detoxifying enzymes and antioxidants. Posttranscriptional regulation and posttranslational modifications also play important roles for maize to adapt to chilling stress. This approach identified new protein species involved in posttranslational modifications, signal transduction, lipid metabolism, inorganic ion transport and metabolism and other biological processes that were not previously known to be associated with chilling stress response. [ABSTRACT FROM AUTHOR]

Key message: A Sec14-like protein, ZmSEC14p , from maize was structurally analyzed and functionally tested. Overexpression of ZmSEC14p in transgenic Arabidopsis conferred tolerance to cold stress. Abstract: Sec14-like proteins are involved in essential biological processes, such as phospholipid metabolism, signal transduction, membrane trafficking, and stress response. Here, we reported a phosphatidylinositol transfer-associated protein, ZmSEC14p (accession no. KT932998), isolated from a cold-tolerant maize inbred line using the cDNA-AFLP approach and RACE-PCR method. Full-length cDNA that consisted of a single open reading frame (ORF) encoded a putative polypeptide of 295 amino acids. The ZmSEC14p protein was mainly localized in the nucleus, and its transcript was induced by cold, salt stresses, and abscisic acid (ABA) treatment in maize leaves and roots. Overexpression of ZmSEC14p in transgenic Arabidopsis conferred tolerance to cold stress. This tolerance was primarily displayed by the increased germination rate, root length, plant survival rate, accumulation of proline, activities of antioxidant enzymes, and the reduction of oxidative damage by reactive oxygen species (ROS). ZmSEC14p overexpression regulated the expression of phosphoinositide-specific phospholipase C, which cleaves phosphatidylinositol 4,5-bisphosphate (PIP2) and generates second messengers (inositol 1,4,5-trisphosphate and 1,2-diacylglycerol) in the phosphoinositide signal transduction pathways. Moreover, up-regulation of some stress-responsive genes such as CBF3, COR6.6, and RD29B in transgenic plants under cold stress could be a possible mechanism for enhancing cold tolerance. Taken together, this study strongly suggests that ZmSEC14p plays an important role in plant tolerance to cold stress. [ABSTRACT FROM AUTHOR]

A bimodal imaging probe FCy7‐NO2 was applied to image nitroreductase overexpressed by lung cancer in vivo, as reported by Xin Zhou and co‐workers in their Research Article (e202213495). Integrating two complementary imaging technologies into FCy7‐NO2 enables sensitive detection of nitroreductase over a broad concentration range without tissue‐depth limit. [ABSTRACT FROM AUTHOR]

Inside Back Cover: In Vivo Nitroreductase Imaging via Fluorescence and Chemical Shift Dependent 19F NMR (Angew. Integrating two complementary imaging technologies into FCy7-NO SB 2 sb enables sensitive detection of nitroreductase over a broad concentration range without tissue-depth limit. 19F MRI, Biosensors, Fluorescence Imaging, Hypoxia, Nitroreductase. [Extracted from the article]

Eine bimodale Bildgebungssonde FCy7‐NO2 wurde eingesetzt, um die bei Lungenkrebs überexprimierte Nitroreduktase in vivo abzubilden, wie Xin Zhou et al. in ihrem Forschungsartikel berichten (e202213495). Die Integration zweier komplementärer Bildgebungstechnologien in FCy7‐NO2 ermöglicht einen empfindlichen Nachweis von Nitroreduktase in einem breiten Konzentrationsbereich ohne Gewebetiefenbegrenzung. [ABSTRACT FROM AUTHOR]

Keywords: 19F MRI; Biosensors; Fluorescence Imaging; Hypoxia; Nitroreductase EN 19F MRI Biosensors Fluorescence Imaging Hypoxia Nitroreductase 1 1 1 12/07/22 20221212 NES 221212 B Eine bimodale Bildgebungssonde b FCy7-NO SB 2 sb wurde eingesetzt, um die bei Lungenkrebs überexprimierte Nitroreduktase in vivo abzubilden, wie Xin Zhou et al. in ihrem Forschungsartikel berichten (e202213495). 19F MRI, Biosensors, Fluorescence Imaging, Hypoxia, Nitroreductase Die Integration zweier komplementärer Bildgebungstechnologien in FCy7-NO SB 2 sb ermöglicht einen empfindlichen Nachweis von Nitroreduktase in einem breiten Konzentrationsbereich ohne Gewebetiefenbegrenzung. [Extracted from the article]

Intact somatic embryos were obtained from an elite maize inbred line Y423, bred in our laboratory. Using 13-day immature embryos after self-pollination as explants, and after 4–5 times subculture, a large number of somatic embryos were detected on the surface of the embryonic calli on the medium. The intact somatic embryos were transferred into the differential medium, where the plantlets regenerated with shoots and roots forming simultaneously. Histological analysis and scanning electron micrographs confirmed the different developmental stages of somatic embryogenesis, including globular-shaped embryo, pear-shaped embryo, scutiform embryo, and mature embryo. cDNA-amplified fragment length polymorphism (cDNA-AFLP) was used for comparative transcript profiling between embryogenic and non-embryogenic calli of a new elite maize inbred line Y423 during somatic embryogenesis. Differentially expressed genes were cloned and sequenced. Gene Ontology analysis of 117 candidate genes indicated their involvement in cellular component, biological process and molecular function. Nine of the candidate genes were selected. The changes in their expression levels during embryo induction and regeneration were analyzed in detail using quantitative real-time PCR. Two full-length cDNA sequences, encoding ZmSUF4 (suppressor of fir 4-like protein) and ZmDRP3A (dynamin-related protein), were cloned successfully from intact somatic embryos of the elite inbred maize line Y423. Here, a procedure for maize plant regeneration from somatic embryos is described. Additionally, the possible roles of some of these genes during the somatic embryogenesis has been discussed. This study is a systematic analysis of the cellular and molecular mechanism during the formation of intact somatic embryos in maize. [ABSTRACT FROM AUTHOR]