Publications by authors named "Hongbo Yuan"

40 Publications

Structure and Dynamics of a Temperature-Sensitive Hydrogel.

J Phys Chem B 2021 07 19;125(29):8219-8224. Epub 2021 Jul 19.

AMOLF, Science Park 104, 1098 XG Amsterdam, The Netherlands.

Polyisocyanotripeptides (TriPIC) are biomimetic polymers which consist of a β-helical backbone stabilized by hydrogen bonds between amide groups. Their oligoethylene glycol side chains give aqueous TriPIC solutions a thermoresponsive behavior: at 50 °C the solution becomes a hydrogel. In this paper we study the molecular structure and water dynamics of TriPIC aqueous solutions while undergoing gelation using FT-IR spectroscopy and polarization-resolved femtosecond infrared spectroscopy (fs-IR). We find evidence that the oligoethylene glycol side chains trap part of the water molecules upon gel formation, and we propose that the interaction between the oligoethylene glycol side chains and water plays an essential role in the bundling of the polymers and thus in the formation of a hydrogel.
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http://dx.doi.org/10.1021/acs.jpcb.1c03121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327313PMC
July 2021

Grape Leaf Black Rot Detection Based on Super-Resolution Image Enhancement and Deep Learning.

Front Plant Sci 2021 29;12:695749. Epub 2021 Jun 29.

College of Mechanical and Electrical Engineering, Hebei Agricultural University, Baoding, China.

The disease spots on the grape leaves can be detected by using the image processing and deep learning methods. However, the accuracy and efficiency of the detection are still the challenges. The convolutional substrate information is fuzzy, and the detection results are not satisfactory if the disease spot is relatively small. In particular, the detection will be difficult if the number of pixels of the spot is <32 × 32 in the image. In order to effectively address this problem, we present a super-resolution image enhancement and convolutional neural network-based algorithm for the detection of black rot on grape leaves. First, the original image is up-sampled and enhanced with local details using the bilinear interpolation. As a result, the number of pixels in the image increase. Then, the enhanced images are fed into the proposed YOLOv3-SPP network for detection. In the proposed network, the IOU (Intersection Over Union, IOU) in the original YOLOv3 network is replaced with GIOU (Generalized Intersection Over Union, GIOU). In addition, we also add the SPP (Spatial Pyramid Pooling, SPP) module to improve the detection performance of the network. Finally, the official pre-trained weights of YOLOv3 are used for fast convergence. The test set test_pv from the Plant Village and the test set test_orchard from the orchard field were used to evaluate the network performance. The results of test_pv show that the grape leaf black rot is detected by the YOLOv3-SPP with 95.79% detection accuracy and 94.52% detector recall, which is a 5.94% greater in terms of accuracy and 10.67% greater in terms of recall as compared to the original YOLOv3. The results of test_orchard show that the method proposed in this paper can be applied in field environment with 86.69% detection precision and 82.27% detector recall, and the accuracy and recall were improved to 94.05 and 93.26% if the images with the simple background. Therefore, the detection method proposed in this work effectively solves the detection task of small targets and improves the detection effectiveness of the grape leaf black rot.
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http://dx.doi.org/10.3389/fpls.2021.695749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8277438PMC
June 2021

Occurrence and Detection of Carbendazim-Resistance in Botryosphaeria dothidea from apple orchards in China.

Plant Dis 2021 Jul 6. Epub 2021 Jul 6.

Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, Henan Provincial Key Laboratory of Fruit and Cucurbit Biology, East Hanghai Road, Zhengzhou, Zhengzhou, China, 450009;

Botryosphaeria dothidea causes white rot, which is among the most devastating diseases affecting apple crops globally. In this paper, we assessed B. dothidea resistance to carbendazim by collecting samples from warts on the infected branches of apple trees or from fruits exhibiting evidence of white rot. All samples were collected from different orchards of nine provinces of China in 2018 and 2019. In total 440 B. dothidea isolates were evaluated, of which 19 isolates from three provinces were found to exhibit carbendazim-resistance. We additionally explored the fitness and resistance stability of these isolates, revealing that they were no less fit than carbendazim-sensitive isolates in terms of pathogenicity, sporulation, and mycelial growth and that the observed carbendazim resistance was stable. Sequencing of the β-tubulin gene in carbendazim-resistant isolates showed the presence of a substitution at codon 198 (GAG to GCG) that result in an alanine substitution in place of glutamic acid (E198A) in all 19 resistant isolates. A LAMP method was then developed to rapidly and specifically identify this E198A mutation. This LAMP method offers value as a tool for rapidly detecting carbendazim-resistant isolates bearing this E198A mutation, and can thus be used for the widespread monitoring of apple crops to detect and control the development of such resistance.
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http://dx.doi.org/10.1094/PDIS-06-20-1204-REDOI Listing
July 2021

Property Regulation of Conjugated Oligoelectrolytes with Polyisocyanide to Achieve Efficient Photodynamic Antibacterial Biomimetic Hydrogels.

ACS Appl Mater Interfaces 2021 Jun 14;13(24):27955-27962. Epub 2021 Jun 14.

Institute of Biophysics, Hebei University of Technology, Tianjin 300401, P. R. China.

Fabricating antibacterial hydrogels with antimicrobial drugs and synthetic biocompatible biomimetic hydrogels is a promising strategy for practical medical applications. Here, we report a bicomponent hydrogel composed of a biomimetic polyisocyanopetide (PIC) hydrogel and a photodynamic antibacterial membrane-intercalating conjugated oligoelectrolyte (COE). The aggregation behavior and aggregate size of the COEs in water can be regulated using the PIC hydrogel, which could induce COEs with higher reactive oxygen species (ROS) production efficiency and increased association of COEs toward bacteria, therefore enhancing the antibacterial efficiency. This strategy provides a facile method for developing biomimetic hydrogels with high antibacterial capability.
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http://dx.doi.org/10.1021/acsami.1c06659DOI Listing
June 2021

Impact of acute kidney injury on in-hospital outcomes in Chinese patients with community acquired pneumonia.

BMC Pulm Med 2021 May 1;21(1):143. Epub 2021 May 1.

Department of Nephrology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, Jiangsu, China.

Background: Acute kidney injury (AKI) is a frequent complication of community acquired pneumonia (CAP). However, the impact of AKI on in-hospital outcomes of patients with CAP in the Chinese population remains unclear.

Methods: Patients diagnosed with CAP were evaluated in this retrospective observational study. Multiple Cox regression models were employed to identify the association between AKI and in-hospital mortality and 30-day mortality, respectively.

Results: A total of 4213 patients were recruited; 950 (22.5%) patients were diagnosed with AKI. Independent risk factors for AKI were age, male gender, hypertension, cardiac dysfunction, diabetes, chronic kidney disease, acute respiratory failure, use of diuretics, use of vasoactive drugs, and CURB-65. Cox proportional hazards regression revealed AKI, use of angiotensin receptor blocker, hypertension, CURB-65, acute respiratory failure, and use of vasoactive drugs to be independent risk factors for both in-hospital and 30-day mortality. Compared to patients without AKI, those suffering AKI were found to have 1.31-fold (HR 1.31, 95% CI, 1.04-1.66; P = 0.023) and 1.29-fold (HR 1.29, 95% CI, 1.02-1.62; P = 0.033) increased in-hospital and 30-day mortality risks, respectively. In addition, patients with AKI were likely to require admission to intensive care unit (ICU) (42.9% versus 11.4%; P < 0.001), mechanical ventilation (33.8% versus 9.3%; P < 0.001), invasive mechanical ventilation (25.9% versus 5.8%; P < 0.001), non-invasive mechanical ventilation (25.4% versus 7.1%; P < 0.001), and experienced a longer duration of hospital stay (14 days versus 10 days; P < 0.001) than those without AKI. However, no significant difference in ICU stay (11 days versus 10 days; P = 0.099) and duration of mechanical ventilation (8 days versus 8 days; P = 0.369) between AKI and non-AKI groups was found.

Conclusion: AKI was common in Chinese patients with CAP. Patients with CAP who developed AKI had worse in-hospital outcomes.
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http://dx.doi.org/10.1186/s12890-021-01511-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8088559PMC
May 2021

LDPE and HDPE Microplastics Differently Affect the Transport of Tetracycline in Saturated Porous Media.

Materials (Basel) 2021 Apr 2;14(7). Epub 2021 Apr 2.

Key Laboratory of Pollution Ecology and Environmental Engineering, Institute of Applied Ecology, Chinese Academy of Sciences, Shenyang 110016, China.

The accumulation of microplastics (MPs) in soil and sediments may influence the penetration of contaminants into subsurface environments. However, little attention has been paid to comparing the different roles of two common polyethylene (PE) types-low-density polyethylene (LDPE) and high-density polyethylene (HDPE). In this study, the transport behaviors of tetracycline in saturated quartz sand columns in the presence and absence of these two MPs were investigated, respectively. The results showed that both types of PE MPs restrained the mobility of tetracycline at neutral conditions, while such detrimental effects were weak at acid and alkaline conditions. The degree of nonequilibrium adsorption was higher, and tetracycline transferred easier to the kinetic site for the existence of LDPE than of HDPE. The increased roughness and Brunauer-Emmett-Teller (BET) surface areas, more negative zeta potentials and the formation of oxygen function groups on the surface of MPs after UV-weathering intensified the retardation of tetracycline transport. This study revealed that the PE type and weathering should be taken into account in risk assessment, along with the solution chemistry.
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http://dx.doi.org/10.3390/ma14071757DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8038232PMC
April 2021

How well can we assess the validity of non-randomised studies of medications? A systematic review of assessment tools.

BMJ Open 2021 03 24;11(3):e043961. Epub 2021 Mar 24.

Real World Evidence Sciences, Visible Analytics Ltd, Oxford, UK.

Objective: To determine whether assessment tools for non-randomised studies (NRS) address critical elements that influence the validity of NRS findings for comparative safety and effectiveness of medications.

Design: Systematic review and Delphi survey.

Data Sources: We searched PubMed, Embase, Google, bibliographies of reviews and websites of influential organisations from inception to November 2019. In parallel, we conducted a Delphi survey among the International Society for Pharmacoepidemiology Comparative Effectiveness Research Special Interest Group to identify key methodological challenges for NRS of medications. We created a framework consisting of the reported methodological challenges to evaluate the selected NRS tools.

Study Selection: Checklists or scales assessing NRS.

Data Extraction: Two reviewers extracted general information and content data related to the prespecified framework.

Results: Of 44 tools reviewed, 48% (n=21) assess multiple NRS designs, while other tools specifically addressed case-control (n=12, 27%) or cohort studies (n=11, 25%) only. Response rate to the Delphi survey was 73% (35 out of 48 content experts), and a consensus was reached in only two rounds. Most tools evaluated methods for selecting study participants (n=43, 98%), although only one addressed selection bias due to depletion of susceptibles (2%). Many tools addressed the measurement of exposure and outcome (n=40, 91%), and measurement and control for confounders (n=40, 91%). Most tools have at least one item/question on design-specific sources of bias (n=40, 91%), but only a few investigate reverse causation (n=8, 18%), detection bias (n=4, 9%), time-related bias (n=3, 7%), lack of new-user design (n=2, 5%) or active comparator design (n=0). Few tools address the appropriateness of statistical analyses (n=15, 34%), methods for assessing internal (n=15, 34%) or external validity (n=11, 25%) and statistical uncertainty in the findings (n=21, 48%). None of the reviewed tools investigated all the methodological domains and subdomains.

Conclusions: The acknowledgement of major design-specific sources of bias (eg, lack of new-user design, lack of active comparator design, time-related bias, depletion of susceptibles, reverse causation) and statistical assessment of internal and external validity is currently not sufficiently addressed in most of the existing tools. These critical elements should be integrated to systematically investigate the validity of NRS on comparative safety and effectiveness of medications. SYSTEMATIC REVIEW PROTOCOL AND REGISTRATION: https://osf.io/es65q.
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http://dx.doi.org/10.1136/bmjopen-2020-043961DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7993210PMC
March 2021

Identification and Detection of from Kiwifruit () in China.

Plants (Basel) 2021 Feb 20;10(2). Epub 2021 Feb 20.

Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, Zhengzhou 450009, China.

Kiwifruit is very popular among consumers due to its high nutritional value. The increasing expansion in kiwifruit cultivation has led to the spread of rot diseases. To identify the pathogens causing kiwifruit ripe rots in China, 24 isolates were isolated from the diseased fruit and wart in trees. was recognized as the pathogen causing kiwifruit ripe rot and wart in the tree through internal transcribed spacer (ITS) sequencing, pathogenicity testing, morphological and microscopic characteristics. The rapid and accurate detection of this pathogen will lead to better disease monitoring and control efforts. A loop-mediated isothermal amplification (LAMP) method was then developed to rapidly and specifically identify . These results offer value to further research into kiwifruit ripe rot, such as disease prediction, pathogen rapid detection, and effective disease control.
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http://dx.doi.org/10.3390/plants10020401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923295PMC
February 2021

Agrobacterium tumefaciens-mediated transformation of Coniella granati.

J Microbiol Methods 2021 03 22;182:106149. Epub 2021 Jan 22.

Zhengzhou Fruit Research Institute, Chinese Academy of Agricultural Sciences, Zhengzhou 450009, China. Electronic address:

Pomegranate fruit rot caused by Coniella granati is among the most devastating diseases threatening pomegranate production. The pathogenic mechanism of this pathogen remains largely unknown due to lack of genetic transformation method. Herein, we developed an approach to the Agrobacterium tumefaciens-mediated transformation (ATMT) of C. granati using a plasmid vector encoding the green fluorescent protein (GFP) and hygromycin resistance (Hyg) genes. This approach yielded C. granati transformants that exhibited uniform, stable green fluorescence. We further optimized this ATMT protocol, enabling us to achieve a transformation efficiency of up to 300 transformants per 0.5 cm mycelial plug. Together, we thus provide the first report of the stable transformation of C. granati, laying a foundation for future functional studies characterizing this economically important fungal pathogen.
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http://dx.doi.org/10.1016/j.mimet.2021.106149DOI Listing
March 2021

SnRK1 Phosphorylates and Destabilizes WRKY3 to Enhance Barley Immunity to Powdery Mildew.

Plant Commun 2020 Jul 9;1(4):100083. Epub 2020 Jun 9.

State Key Laboratory of Plant Cell and Chromosome Engineering, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Innovation Academy for Seed Design, Beijing 100101, China.

Plants recognize pathogens and activate immune responses, which usually involve massive transcriptional reprogramming. The evolutionarily conserved kinase, Sucrose non-fermenting-related kinase 1 (SnRK1), functions as a metabolic regulator that is essential for plant growth and stress responses. Here, we identify barley SnRK1 and a WRKY3 transcription factor by screening a cDNA library. SnRK1 interacts with WRKY3 in yeast, as confirmed by pull-down and luciferase complementation assays. Förster resonance energy transfer combined with noninvasive fluorescence lifetime imaging analysis indicates that the interaction occurs in the barley nucleus. Transient expression and virus-induced gene silencing analyses indicate that WRKY3 acts as a repressor of disease resistance to the fungus. Barley plants overexpressing have enhanced fungal microcolony formation and sporulation. Phosphorylation assays show that SnRK1 phosphorylates WRKY3 mainly at Ser83 and Ser112 to destabilize the repressor, and WRKY3 non-phosphorylation-null mutants at these two sites are more stable than the wild-type protein. SnRK1-overexpressing barley plants display enhanced disease resistance to . Transient expression of SnRK1 reduces fungal haustorium formation in barley cells, which probably requires SnRK1 nuclear localization and kinase activity. Together, these findings suggest that SnRK1 is directly involved in plant immunity through phosphorylation and destabilization of the WRKY3 repressor, revealing a new regulatory mechanism of immune derepression in plants.
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http://dx.doi.org/10.1016/j.xplc.2020.100083DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747994PMC
July 2020

Framework for the synthesis of non-randomised studies and randomised controlled trials: a guidance on conducting a systematic review and meta-analysis for healthcare decision making.

BMJ Evid Based Med 2020 Dec 9. Epub 2020 Dec 9.

Julius Center for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands.

Introduction: High-quality randomised controlled trials (RCTs) provide the most reliable evidence on the comparative efficacy of new medicines. However, non-randomised studies (NRS) are increasingly recognised as a source of insights into the real-world performance of novel therapeutic products, particularly when traditional RCTs are impractical or lack generalisability. This means there is a growing need for synthesising evidence from RCTs and NRS in healthcare decision making, particularly given recent developments such as innovative study designs, digital technologies and linked databases across countries. Crucially, however, no formal framework exists to guide the integration of these data types.

Objectives And Methods: To address this gap, we used a mixed methods approach (review of existing guidance, methodological papers, Delphi survey) to develop guidance for researchers and healthcare decision-makers on when and how to best combine evidence from NRS and RCTs to improve transparency and build confidence in the resulting summary effect estimates.

Results: Our framework comprises seven steps on guiding the integration and interpretation of evidence from NRS and RCTs and we offer recommendations on the most appropriate statistical approaches based on three main analytical scenarios in healthcare decision making (specifically, 'high-bar evidence' when RCTs are the preferred source of evidence, 'medium,' and 'low' when NRS is the main source of inference).

Conclusion: Our framework augments existing guidance on assessing the quality of NRS and their compatibility with RCTs for evidence synthesis, while also highlighting potential challenges in implementing it. This manuscript received endorsement from the International Society for Pharmacoepidemiology.
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http://dx.doi.org/10.1136/bmjebm-2020-111493DOI Listing
December 2020

Inhibition and disaggregation of amyloid β protein fibrils through conjugated polymer-core thermoresponsive micelles.

J Mater Chem B 2020 11;8(44):10126-10135

School of Materials Science and Engineering, Hebei University of Technology, Tianjin 300401, P. R. China.

Excess aggregation of amyloid β peptide (Aβ) is a fatal cause of Alzheimer's disease (AD), which leads to physiological toxicity. Inhibiting and disaggregating the Aβ aggregates is an effective strategy to reduce physiological toxicity in neuronal cells. Herein, conjugated polymer-based thermoresponsive micelles (CPMs) were designed with an efficient thermoresponsive surface and a reactive-oxygen-species (ROS)-generating core. In this work, the CPMs exhibited a strong capability to capture the toxic Aβ aggregates at physiological temperature. Under white-light irradiation, ROS was generated in the CPMs, and the toxic Aβ aggregates were efficiently disaggregated through the oxidation of ROS, leading to appropriate Aβ homeostasis between aggregation and disaggregation and reduced the Aβ-induced cytotoxicity. Therefore, the multifunctional micelles of CPMs with both capturing shells and ROS functional cores present a promising strategy to reduce Aβ fibrillation-induced cytotoxicity.
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http://dx.doi.org/10.1039/d0tb01863eDOI Listing
November 2020

Serum cystatin C: A potential predictor for hospital-acquired acute kidney injury in patients with acute exacerbation of COPD.

Chron Respir Dis 2020 Jan-Dec;17:1479973120940677

Department of Nephrology, 385685Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu, China.

Hospital-acquired acute kidney injury (HA-AKI) is associated with poor prognosis. In this study, we evaluated whether serum cystatin C on admission could predict AKI in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). The retrospective study was conducted using data on adult inpatients with AECOPD from January 2014 to January 2017. A total of 1035 patients were included, among which 79 (7.6%) with HA-AKI were identified. Univariate and multivariate logistic regression analyses were used to investigate predictors of HA-AKI in patients with AECOPD. HA-AKI was associated with poor prognosis, and patients with HA-AKI had higher inpatient mortality (34.2% vs. 2.6%, < 0.001). Furthermore, after adjusting for confounders, HA-AKI was an independent risk factor for inpatient mortality for patients with AECOPD (odds ratio (OR) 11.02; 95% confidence interval (CI) 4.77-25.45; < 0.001). Four independent risk factors for HA-AKI (age, levels of urea and cystatin C, and platelet count on admission) were identified in patients with AECOPD. Cystatin C (OR 5.22; 95% CI 2.49-10.95; < 0.001) was a significant independent predictor of AKI in patients with AECOPD. HA-AKI in patients with AECOPD could be identified with a sensitivity of 73.5% and a specificity of 75.9% (area under the curve (AUC) = 0.803, 95% CI 0.747-0.859) by cystatin C level (cutoff value = 1.3 mg/L) and with a sensitivity of 75.9% and a specificity of 82.0% (AUC = 0.853, 95% CI 0.810-0.896) using a model comprising all significant predictors. Serum cystatin C has the potential for use to predict the risk of HA-AKI in patients with AECOPD.
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http://dx.doi.org/10.1177/1479973120940677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7493270PMC
September 2020

Comparison of dexmedetomidine with chloral hydrate as sedatives for pediatric patients: A systematic review and meta-analysis.

Medicine (Baltimore) 2020 Jul;99(31):e21008

Department of Pharmacy.

Background: Dexmedetomidine (Dex) and chloral hydrate (CH) are the most frequently used sedative agents in pediatric patients. We aimed to systematically review the literature comparing the efficacy and safety of Dex and CH for sedation in pediatric patients.

Methods: Seven electronic databases and 3 clinical trial registry platforms were searched for articles published prior to October 2019. Randomized controlled trials (RCTs) evaluating the efficacy and safety of Dex versus CH for sedation in children were examined by 2 reviewers. The extracted information included the success rate of sedation, sedation latency, sedation duration, sedation recovery time, and adverse events. Moreover, the extracted data included 5 subgroups: the effects of 1, 1.5, 2, 2.5, and 3 μg/kg doses of Dex were compared with the effect of CH on the success rate of sedation. We also formed separate subgroups for different types of adverse events (incidence of vomiting, hypotension, bradycardia, etc). The outcomes were analyzed by Review Manager 5.3 software and are expressed as relative risks (RR) or the mean difference (MD) with the 95% confidence interval (CI). Heterogeneity was assessed with I-squared (I) statistics.

Results: A total of 15 RCTs involving 2128 children with Dex versus CH for sedation were included in the meta-analysis. The dose range of Dex ranged from 1 to 3 μg/kg. Compared with CH, the Dex group had a significantly higher success rate of sedation (RR = 1.14, 95% CI [1.05, 1.25], I = 79%, P = .003). Additionally, subgroup analysis revealed that there was no significant difference in the success rate of sedation between the CH group and the 1, 1.5, 2.5, and 3 μg/kg Dex groups; only the 2 μg/kg Dex group had a significantly higher success rate than the CH group (RR = 1.15, 95% CI [1.03, 1.29], I = 80%, P = .02). There was no significant difference in the number of subjects who required 2 doses or the duration of sedation between the CH and Dex groups. Furthermore, compared with the Dex group, the CH group had a significantly longer sedation latency (MD = -3.54, 95% CI [-5.94, -1.15], I = 95%, P = .004), sedation recovery time (MD = -30.08, 95% CI [-46.77, -13.39], I = 99%, P = .0004), and total time from sedative administration to discharge (MD = -12.73, 95% CI [-15.48, -9.97], I = 0%, P < .05), as well as a higher number of adverse events in total (RR = 0.25, 95% CI [0.11, 0.61], I = 89%, P = .002). Moreover, the subgroup analysis of adverse events revealed that CH was associated with higher risks of vomiting (RR = 0.07, 95% CI [0.03, 0.17], I = 0%, P < .0001), crying or resisting (RR = 0.22, 95% CI [0.07, 0.71], I = 60%, P = .01), and cough (RR = 0.15, 95% CI [0.05, 0.44], I = 0%, P = .0006); there was no significant difference in the risk of hypotension, supplemental oxygen, or respiratory events between CH and Dex. However, Dex was associated with a higher risk of bradycardia (RR = 4.08, 95% CI [1.63, 10.21], I = 0%, P = .003).

Conclusions: Dex is an appropriate effective alternative to CH for sedation in pediatrics. However, considering the possibility of bradycardia, Dex should be used with caution.
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http://dx.doi.org/10.1097/MD.0000000000021008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7402776PMC
July 2020

Biomimetic Networks with Enhanced Photodynamic Antimicrobial Activity from Conjugated Polythiophene/Polyisocyanide Hybrid Hydrogels.

Angew Chem Int Ed Engl 2020 02 9;59(7):2720-2724. Epub 2020 Jan 9.

Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ, Nijmegen, The Netherlands.

Hybrid biomimetic hydrogels with enhanced reactive oxygen species (ROS)-generation efficiency under 600 nm light show high antibacterial activity. The hybrid gels are composed of helical tri(ethylene glycol)-functionalized polyisocyanides (PICs) and a conformation-sensitive conjugated polythiophene, poly(3-(3'-N,N,N-triethylammonium-1'-propyloxy)-4-methyl-2,5-thiophene chloride) (PMNT). The PIC polymer serves as a scaffold to trap and align the PMNT backbone into a highly ordered conformation, resulting in redshifted, new sharp bands in the absorption and fluorescence spectra. Similar to PIC, the hybrid closely mimics the mechanical properties of biological gels, such as collagen and fibrin, including the strain stiffening properties at low stresses. Moreover, the PMNT/PIC hybrids show much higher ROS production efficiency under red light than PMNT only, leading to an efficient photodynamic antimicrobial effect towards various pathogenic bacteria.
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http://dx.doi.org/10.1002/anie.201910979DOI Listing
February 2020

Development of a Peanut Canopy Measurement System Using a Ground-Based LiDAR Sensor.

Front Plant Sci 2019 28;10:203. Epub 2019 Feb 28.

USDA-ARS, Wheat, Peanuts and Other Field Crops Research Unit, Stillwater, OK, United States.

Plant architecture characteristics contribute significantly to the microclimate within peanut canopies, affecting weed suppression as well as incidence and severity of foliar and soil-borne diseases. However, plant canopy architecture is difficult to measure and describe quantitatively. In this study, a ground-based LiDAR sensor was used to scan rows of peanut plants in the field, and a data processing and analysis algorithm was developed to extract feature indices to describe the peanut canopy architecture. A data acquisition platform was constructed to carry the ground-based LiDAR and an RGB camera during field tests. An experimental field was established with three peanut cultivars at Oklahoma State University's Caddo Research Station in Fort Cobb, OK in May and the data collections were conducted once each month from July to September 2015. The ground-based LiDAR used for this research was a line-scan laser scanner with a scan-angle of 100°, an angle resolution of 0.25°, and a scanning speed of 53 ms. The collected line-scanned data were processed using the developed image processing algorithm. The canopy height, width, and shape/density were evaluated. Euler number, entropy, cluster count, and mean number of connected objects were extracted from the image and used to describe the shape of the peanut canopies. The three peanut cultivars were then classified using the shape features and indices. A high correlation was also observed between the LiDAR and ground-truth measurements for plant height. This approach should be useful for phenotyping peanut germplasm for canopy architecture.
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http://dx.doi.org/10.3389/fpls.2019.00203DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6403138PMC
February 2019

Dual inhibitors of RAF-MEK-ERK and PI3K-PDK1-AKT pathways: Design, synthesis and preliminary anticancer activity studies of 3-substituted-5-(phenylamino) indolone derivatives.

Bioorg Med Chem 2019 03 26;27(6):944-954. Epub 2019 Jan 26.

Department of Medicinal Chemistry, Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, Hunan, PR China. Electronic address:

The dysfunction and mutual compensatory activation of RAF-MEK-ERK and PI3K-PDK1-AKT pathways have been demonstrated as the hallmarks in several primary and recurrent cancers. The strategy of concurrent blocking of these two pathways shows clinical merits on effective cancer therapy, such as combinatory treatments and dual-pathway inhibitors. Herein, we report a novel prototype of dual-pathway inhibitors by means of merging the core structural scaffolds of a MEK1 inhibitor and a PDK1 inhibitor. A library of 43 compounds that categorized into three series (Series I-III) was synthesized and tested for antitumor activity in lung cancer cells. The results from structure-activity relationship (SAR) analysis showed the following order of antitumor activity that 3-hydroxy-5-(phenylamino) indolone (Series III) > 3-alkenyl-5-(phenylamino) indolone (Series I) > 3-alkyl-5-(phenylamino) indolone (Series II). A lead compound 9za in Series III showed most potent antitumor activity with IC value of 1.8 ± 0.8 µM in A549 cells. Moreover, antitumor mechanism study demonstrated that 9za exerted significant apoptotic effect, and cellular signal pathway analysis revealed the potent blockage of phosphorylation levels of ERK and AKT in RAF-MEK-ERK and PI3K-PDK1-AKT pathways, respectively. The results reported here provide robust experimental basis for the discovery and optimization of dual pathway agents for anti-lung cancer therapy.
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http://dx.doi.org/10.1016/j.bmc.2019.01.028DOI Listing
March 2019

Remote-Controlling Potassium Channels in Living Cells through Photothermal Inactivation of Calmodulin.

Adv Healthc Mater 2018 10 17;7(19):e1800674. Epub 2018 Aug 17.

Key Laboratory of Organic Solids, Institute of Chemistry, Chinese Academy of Sciences, Beijing, 100190, P. R. China.

Spatiotemporal regulation of cellular functions provides a powerful strategy for understanding underlying mechanisms of cellular bioprocesses. Here, a strategy is reported to realize the remote control of the activities of potassium channels via photothermal inactivation of calmodulin (CaM) by using reduced graphene oxide decorated with calmodulin binding peptide (rGO-P) as the transducer with near-infrared light (NIR) irradiation. Upon NIR light irradiation, the CaM/Ca bound to rGO-P is inactivated by the photothermal effect of rGO-P, resulting in the incapability of binding with Ca . Hence, the closed Kv10.1 channel is converted to be open in the presence of calcium in living cells. Meanwhile, the SK2 channel is induced to be closed from the open state and the Kir2.1 channel is unaffected by the intracellular inactivation of CaM. This strategy gives a noninvasive and effective approach to remotely control the activities of potassium channels, offering an alternative for the development of optogenetics.
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http://dx.doi.org/10.1002/adhm.201800674DOI Listing
October 2018

Real-World Evidence: What It Is and What It Can Tell Us According to the International Society for Pharmacoepidemiology (ISPE) Comparative Effectiveness Research (CER) Special Interest Group (SIG).

Clin Pharmacol Ther 2018 08 7;104(2):239-241. Epub 2018 May 7.

Department of Pharmacoepidemiology, Takeda Pharmaceuticals International Co., Cambridge, Massachusetts, USA.

On December 8, 2016, the New England Journal of Medicine published a sounding board on Real World Evidence (RWE) by the US Food and Drug Administration (FDA) leadership. While the value of RWE based on nonrandomized observational studies was appreciated, such as for hypothesis generating, safety, and measuring quality in healthcare delivery, the authors expressed concerns on the quality of data sources and the ability of methodologies to control for confounding. In response, we offer a few considerations regarding these concerns.
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http://dx.doi.org/10.1002/cpt.1086DOI Listing
August 2018

Strategies To Increase the Thermal Stability of Truly Biomimetic Hydrogels: Combining Hydrophobicity and Directed Hydrogen Bonding.

Macromolecules 2017 Nov 15;50(22):9058-9065. Epub 2017 Nov 15.

Institute for Molecules and Materials (IMM), Radboud University, Heyendaalseweg 135, 6525AJ Nijmegen, The Netherlands.

Enhancing the thermal stability of proteins is an important task for protein engineering. There are several ways to increase the thermal stability of proteins in biology, such as greater hydrophobic interactions, increased helical content, decreased occurrence of thermolabile residues, or stable hydrogen bonds. Here, we describe a well-defined polymer based on β-helical polyisocyanotripeptides (TriPIC) that uses biological approaches, including hydrogen bonding and hydrophobic interactions for its exceptional thermal stability in aqueous solutions. The multiple hydrogen bonding arrays along the polymer backbone shield the hydrophobic core from water. Variable temperature CD and FTIR studies indicate that, on heating, a better packed polymer conformation further stiffens the backbone. Driven by hydrophobic interactions, TriPIC solutions give fully reversible hydrogels that can withstand high temperatures (80 °C) for extended times. Cryo-scanning electron microscopy (cryo-SEM), small-angle X-ray scattering (SAXS), and thorough rheological analysis show that the hydrogel has a bundled architecture, which gives rise to strain stiffening effects on deformation of the gel, analogous to many biological hydrogels.
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http://dx.doi.org/10.1021/acs.macromol.7b01832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707627PMC
November 2017

A Multiple-Stimulus-Responsive Biomimetic Assembly Based on a Polyisocyanopeptide and Conjugated Polymer.

Chem Asian J 2017 Nov 27;12(22):2962-2966. Epub 2017 Oct 27.

Institute of Biophysics, Hebei University of Technology, Tianjin, 300401, P.R. China.

An assembly was fabricated and was revealed to be a multiple-stimulus-responsive biomimetic hybrid polymer architecture. It was constructed by the hydrophobic interactions between a conjugated polyfluorene that contained 2,1,3-benzothiadiazole units (PFBT) and a tri(ethylene glycol)-functionalized polyisocyanopeptide (3OEG-PIC). The introduction of PFBT to the polyisocyanopeptide (PIC) network allowed for the incorporation of responsiveness to multiple stimuli including temperature, CO , carbonic anhydrase, and nonlinear mechanics, which mimics natural processes and interactions. Furthermore, the light-harvesting and signal amplification characteristics of PFBT endowed the supramolecular assembly with the essential function of fluorescence monitoring for biological processes.
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http://dx.doi.org/10.1002/asia.201701280DOI Listing
November 2017

Identification of Resveratrol, an Herbal Compound, as an Activator of the Calcium-Activated Chloride Channel, TMEM16A.

J Membr Biol 2017 Oct 29;250(5):483-492. Epub 2017 Aug 29.

Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, Tianjin, 300401, China.

Calcium-activated chloride channels (CaCCs) play vital roles in a variety of physiological processes. Dysfunction of the CaCCs is implicated in many diseases. Drug discovery targeting at CaCCs has recently become possible with the determination that TMEM16A is the molecular identity of CaCCs. In this study, we demonstrated that resveratrol (RES), a Chinese traditional medicine compound, is a novel activator of TMEM16A. The yellow fluorescence protein quenching assay and measurement of intracellular calcium fluorescence intensity show that RES activates TMEM16A channels in an intracellular Ca-independent way. The data of inside-out patch clamp revealed that RES dose-dependently activates TMEM16A (EC = 47.92 ± 9.35 μM). Furthermore, RES enhanced the contractions of the ileum of guinea pigs by activating the TMEM16A channel, which indicated that RES might be a promising drug for the treatment of gastrointestinal hypomotility. As RES was able to induce TMEM16A channel activation, TMEM16A can be added to the list of RES drug targets.
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http://dx.doi.org/10.1007/s00232-017-9975-9DOI Listing
October 2017

Conjugated Polyelectrolyte-Based New Strategy for in Situ Detection of Carbon Dioxide.

ACS Appl Mater Interfaces 2017 Jun 9;9(24):20313-20317. Epub 2017 Jun 9.

Key Laboratory of Hebei Province for Molecular Biophysics, Institute of Biophysics, Hebei University of Technology , Tianjin 300401, P.R. China.

A conjugated polymer centered on fluorene and 2,1,3-benzothia-diazole (PFBT) is prepared for sensing CO in situ with high sensitivity and low background. Upon introducing CO, the weaker electrostatic repulsion and stronger hydrophobic interactions between neighboring PFBT molecules enhance the interchain contacts compared to that without CO, leading to the energy transfer from fluorene to 2,1,3-benzothia-diazole sites and the emission color shift from blue to green, which is sensitive to sensing CO in atmospheric air with a content of ∼400 ppm. Importantly, PFBT is employed to monitor photosynthesis and respiration upon cycling day and night in situ.
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http://dx.doi.org/10.1021/acsami.7b05410DOI Listing
June 2017

Carbon Dioxide-Controlled Assembly of Water-Soluble Conjugated Polymers Catalyzed by Carbonic Anhydrase.

Macromol Rapid Commun 2017 Mar 24;38(5). Epub 2017 Jan 24.

Key Laboratory of Hebei Province for Molecular Biophysics, Institute of Biophysics, Hebei University of Technology, Tianjin, 300401, P. R. China.

The CO -responsive and biocatalytic assembly based on conjugated polymers has been demonstrated by combining the signal amplification property of the polythiophene derivative (PTP) and the catalytic actions of carbonic anhydrase (CA). CO is applied as a new trigger mode to construct the smart assembly by controlling the electrostatic and hydrophobic interactions between the PTP molecules in aqueous solution, leading to the visible fluorescence changes. Importantly, the assembly transformation of PTP can be specifically and highly accelerated by CA based on the efficient catalytic activity of CA for the inter-conversion between CO and HCO , mimicking the CO -associated biological processes that occurred naturally in living organisms. Moreover, the PTP-based assembly can be applied for biomimetic CO sequestration with fluorescence monitoring in the presence of CA and calcium.
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http://dx.doi.org/10.1002/marc.201600726DOI Listing
March 2017

Conjugated Polymer-Based Hybrid Materials for Turn-On Detection of CO2 in Plant Photosynthesis.

Anal Chem 2016 06 10;88(12):6593-7. Epub 2016 Jun 10.

Institute for Molecules and Materials, Radboud University , Heyendaalseweg 135, 6525 AJ Nijmegen, The Netherlands.

Detection of carbon dioxide (CO2) is of fundamental importance in diverse applications ranging from environmental analysis to agricultural production. In this work, a hybrid probe based on guanidinium-pendent oligofluorene (G-OF) and water-soluble conjugated polythiophene (PTP) has been developed for the turn on detection of CO2 with low background signal, taking advantage of the efficient fluorescence quenching of the tight aggregate of G-OF/PTP. In the presence of CO2, the electrostatic repulsion between G-OF and PTP can be effectively enhanced through protonation of the side chains, leading to the disaggregation and thus the "turn-on" fluorescence. The strategy allows for the light-up visible detection of CO2 with high sensitivity. Importantly, this system is capable of sensitively monitoring the concentration changes of CO2 in the process of the photosynthesis, which represents a concept to monitor the photosynthesis based on water-soluble conjugated polymers.
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http://dx.doi.org/10.1021/acs.analchem.6b01489DOI Listing
June 2016

Two Ca(2+)-Binding Sites Cooperatively Couple Together in TMEM16A Channel.

J Membr Biol 2016 04 26;249(1-2):57-63. Epub 2015 Dec 26.

Key Laboratory of Molecular Biophysics, Hebei Province, Institute of Biophysics, School of Sciences, Hebei University of Technology, 300401, Tianjin, People's Republic of China.

TMEM16A is the molecular basis of calcium-activated chloride channels and shows Ca(2+)-dependent gating. It is critical to understand how the Ca(2+) sensors dynamically control the gate of TMEM16A. However, the detailed mechanism by which the calcium ions bind and open the channel is still obscure. In this study, the authors confirmed that there are two Ca(2+) sensors which cooperatively couple together in TMEM16A. Our data show that mutations at both Ca(2+)-sensitive domains, E447Y and E702Q-E705Q, weaken the Ca(2+) affinity for TMEM16A channel. The EC50 for WT, E447Y, and E702Q-E705Q are 0.53 ± 0.11, 14.5 ± 0.3, and 26.5 ± 3.6 μM, respectively. The triple mutation, including both of the Ca(2+) sensors, E447Y-E702Q-E705Q, with EC50 as 55.6 ± 5.1 μM, results in much further right-shifted dose response curve than the single sensor's mutations (E447Y, E702Q-E705Q) do, which indicates that there is a cooperation between the two Ca(2+)-sensitive domains. We also found that the divalent cations, both Ca(2+) and Sr(2+), share common mechanism of gating the TMEM16A.
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http://dx.doi.org/10.1007/s00232-015-9846-1DOI Listing
April 2016

Conjugated Polythiophene for Rapid, Simple, and High-Throughput Screening of Antimicrobial Photosensitizers.

ACS Appl Mater Interfaces 2015 Jul 6;7(27):14569-72. Epub 2015 Jul 6.

†School of Chemical Engineering and Technology, Hebei University of Technology, Tianjin 300130, P. R. China.

The cationic conjugated poly[3-(3'-N,N,N-triethylamino-1'-propyloxy)-4-methyl-2,5-thiophene hydrochloride] (PMNT) has been developed for high-throughput screening of photodynamic antimicrobial chemotherapy photosensitizers (PSs). The bacterial number can be detected quantitatively by PMNT via various fluorescence quenching efficiencies. The photosensitized inactivation of bacteria is not efficient with ineffective PSs, and thus the bacteria grow exponentially and can be coated tightly by PMNT through electrostatic and hydrophobic interactions, resulting in aggregates and fluorescence quenching of PMNT, whereas, conversely, effective PSs lead to original and strong fluorescence of PMNT. This new platform of high-throughput screening is promising for discovering new PSs.
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http://dx.doi.org/10.1021/acsami.5b04552DOI Listing
July 2015

Unconventionally secreted effectors of two filamentous pathogens target plant salicylate biosynthesis.

Nat Commun 2014 Aug 26;5:4686. Epub 2014 Aug 26.

Department of Plant Pathology, Nanjing Agricultural University, 1 Weigang Road, Nanjing 210095, China.

Plant diseases caused by fungi and oomycetes pose an increasing threat to food security and ecosystem health worldwide. These filamentous pathogens, while taxonomically distinct, modulate host defense responses by secreting effectors, which are typically identified based on the presence of signal peptides. Here we show that Phytophthora sojae and Verticillium dahliae secrete isochorismatases (PsIsc1 and VdIsc1, respectively) that are required for full pathogenesis. PsIsc1 and VdIsc1 can suppress salicylate-mediated innate immunity in planta and hydrolyse isochorismate in vitro. A conserved triad of catalytic residues is essential for both functions. Thus, the two proteins are isochorismatase effectors that disrupt the plant salicylate metabolism pathway by suppressing its precursor. Furthermore, these proteins lack signal peptides, but exhibit characteristics that lead to unconventional secretion. Therefore, this secretion pathway is a novel mechanism for delivering effectors and might play an important role in host-pathogen interactions.
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http://dx.doi.org/10.1038/ncomms5686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4348438PMC
August 2014

Ca2+-controlled assembly for visualized detection of conformation changes of calmodulin.

ACS Appl Mater Interfaces 2014 Sep 26;6(17):14790-4. Epub 2014 Aug 26.

Key Laboratory of Hebei Province for Molecular Biophysics, Institute of Biophysics, Hebei University of Technology , Tianjin 300401, P. R. China.

A new strategy has been designed for visualized detection of the conformation changes of calmodulin bound to target peptide (CaM-M13) based on the conformation sensitive property of a water-soluble conjugated polythiophene derivative (PMNT) and the electrostatic interactions of PMNT/CaM-M13. Interestingly, the direct visualized PMNT color changes under UV irradiation and the turbidity changes of samples in aqueous medium can be applied to detect the conformation changes as well as the controllable assembly of PMNT/CaM-M13 with Ca(2+) in aqueous medium. Because of the specific binding of Ca(2+), the assembly of PMNT/CaM-M13 can be applied to sense calcium as well.
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http://dx.doi.org/10.1021/am504729dDOI Listing
September 2014

Nucleobase-functionalized conjugated polymer for detection of copper(II).

ACS Appl Mater Interfaces 2014 Jun 12;6(12):9601-7. Epub 2014 Jun 12.

Institute of Biophysics, Hebei University of Technology , Tianjin 300401, P. R. China.

In recent years, supramolecular organization of thiophene derivatives, oligo- and polythiophene, have been developed with various designs to achieve complex functions. Here, we describe the synthesis and characterization of a conjugated polymer with thymidine side chain bases and polythiophene backbones (PTT) instead of phosphate bonds in DNA, and the PTT exhibits exceptional fluorescence quenching efficiency upon binding of Cu(2+) ions in aqueous medium, which is suggested to be electron transfer from the π* orbit at the excited state of PTT to the 3d orbit of Cu(2+) ions and subsequent Cu(2+)-mediated interpolymer π-stacking aggregation. Furthermore, Cu(2+) ions can be selectively and easily monitored by the fluorescence quenching of PTT, which can be used for detection of Cu(2+) ions with good selectivity and high sensitivity in aqueous medium. Both experimental and theoretical methods have been devoted to demonstrate the strong affinity and steric interaction of PTT toward Cu(2+). These findings will illustrate new directions for the design of nucleobase-functionalized materials with transition metals responsive activity.
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http://dx.doi.org/10.1021/am502978wDOI Listing
June 2014
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