Publications by authors named "Sheng Feng"

191 Publications

Femtomolar SARS-CoV-2 Antigen Detection Using the Microbubbling Digital Assay with Smartphone Readout Enables Antigen Burden Quantitation and Dynamics Tracking.

medRxiv 2021 Mar 26. Epub 2021 Mar 26.

Background: Little is known about the dynamics of SARS-CoV-2 antigen burden in respiratory samples in different patient populations at different stages of infection. Current rapid antigen tests cannot quantitate and track antigen dynamics with high sensitivity and specificity in respiratory samples.

Methods: We developed and validated an ultra-sensitive SARS-CoV-2 antigen assay with smartphone readout using the Microbubbling Digital Assay previously developed by our group, which is a platform that enables highly sensitive detection and quantitation of protein biomarkers. A computer vision-based algorithm was developed for microbubble smartphone image recognition and quantitation. A machine learning-based classifier was developed to classify the smartphone images based on detected microbubbles. Using this assay, we tracked antigen dynamics in serial swab samples from COVID patients hospitalized in ICU and immunocompromised COVID patients.

Results: The limit of detection (LOD) of the Microbubbling SARS-CoV-2 Antigen Assay was 0.5 pg/mL (10.6 fM) recombinant nucleocapsid (N) antigen or 4000 copies/mL inactivated SARS-CoV-2 virus in nasopharyngeal (NP) swabs, comparable to many rRT-PCR methods. The assay had high analytical specificity towards SARS-CoV-2. Compared to EUA-approved rRT-PCR methods, the Microbubbling Antigen Assay demonstrated a positive percent agreement (PPA) of 97% (95% confidence interval (CI), 92-99%) in symptomatic individuals within 7 days of symptom onset and positive SARS-CoV-2 nucleic acid results, and a negative percent agreement (NPA) of 97% (95% CI, 94-100%) in symptomatic and asymptomatic individuals with negative nucleic acid results. Antigen positivity rate in NP swabs gradually decreased as days-after-symptom-onset increased, despite persistent nucleic acid positivity of the same samples. The computer vision and machine learning-based automatic microbubble image classifier could accurately identify positives and negatives, based on microbubble counts and sizes. Total microbubble volume, a potential marker of antigen burden, correlated inversely with Ct values and days-after-symptom-onset. Antigen was detected for longer periods of time in immunocompromised patients with hematologic malignancies, compared to immunocompetent individuals. Simultaneous detectable antigens and nucleic acids may indicate the presence of replicating viruses in patients with persistent infections.

Conclusions: The Microbubbling SARS-CoV-2 Antigen Assay enables sensitive and specific detection of acute infections, and quantitation and tracking of antigen dynamics in different patient populations at various stages of infection. With smartphone compatibility and automated image processing, the assay is well-positioned to be adapted for point-of-care diagnosis and to explore the clinical implications of antigen dynamics in future studies.
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http://dx.doi.org/10.1101/2021.03.17.21253847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010739PMC
March 2021

CuH-Catalyzed Regio- and Enantioselective Hydrocarboxylation of Allenes: Toward Carboxylic Acids with Acyclic Quaternary Centers.

J Am Chem Soc 2021 Apr 24;143(13):4935-4941. Epub 2021 Mar 24.

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

We report a method to prepare α-chiral carboxylic acid derivatives, including those bearing all-carbon quaternary centers, through an enantioselective CuH-catalyzed hydrocarboxylation of allenes with a commercially available fluoroformate. A broad range of heterocycles and functional groups on the allenes were tolerated in this protocol, giving enantioenriched α-quaternary and tertiary carboxylic acid derivatives in good yields with exclusive branched regioselectivity. The synthetic utility of this approach was further demonstrated by derivatization of the products to afford biologically important compounds, including the antiplatelet drug indobufen.
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http://dx.doi.org/10.1021/jacs.1c01880DOI Listing
April 2021

Effect of common inorganic anions on iron-catalyzed secondary brown carbon formation from guaiacol.

Sci Total Environ 2021 May 22;770:145206. Epub 2021 Jan 22.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, PR China. Electronic address:

Brown carbon (BrC) is the important component of aerosol with strong UV-visible absorbance. However, the formation of BrC is still elusive. Inorganic anions, e.g., Cl, NO and SO, exist ubiquitously in the atmosphere, while their effects on the formation of BrC are poorly understood. In this study, we have systematically investigated the effects of pH (1, 2 and 3), inorganic anion (Cl, NO and SO) and ionic strength (0.1, 0.5 and 1.0 M) on BrC generation process by measuring the optical, aggregation and product properties. Our results clearly show that the three factors strongly affect the BrC formation by influencing the oxidation activity and the complexation capability of different Fe(III) species. Marcus theory was used in this research to calculate the oxidation activity of different Fe(III) species. Among all the species of Fe(III), FeOH is the most reactive form in the BrC formation reaction. Furthermore, the aggregation process of BrC was also studied, which is affected by different anions due to their different concentration and hydrability, and SO exhibits the highest efficiency to induce the aggregation of BrC. This study will deepen our understanding about the natural formation of BrC under environmentally relevant conditions, and be beneficial for controlling the production of atmospheric particulates and the subsequent health effects.
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http://dx.doi.org/10.1016/j.scitotenv.2021.145206DOI Listing
May 2021

Kalman Filter for Spatial-Temporal Regularized Correlation Filters.

IEEE Trans Image Process 2021 2;30:3263-3278. Epub 2021 Mar 2.

We consider visual tracking in numerous applications of computer vision and seek to achieve optimal tracking accuracy and robustness based on various evaluation criteria for applications in intelligent monitoring during disaster recovery activities. We propose a novel framework to integrate a Kalman filter (KF) with spatial-temporal regularized correlation filters (STRCF) for visual tracking to overcome the instability problem due to large-scale application variation. To solve the problem of target loss caused by sudden acceleration and steering, we present a stride length control method to limit the maximum amplitude of the output state of the framework, which provides a reasonable constraint based on the laws of motion of objects in real-world scenarios. Moreover, we analyze the attributes influencing the performance of the proposed framework in large-scale experiments. The experimental results illustrate that the proposed framework outperforms STRCF on OTB-2013, OTB-2015 and Temple-Color datasets for some specific attributes and achieves optimal visual tracking for computer vision. Compared with STRCF, our framework achieves AUC gains of 2.8%, 2%, 1.8%, 1.3%, and 2.4% for the background clutter, illumination variation, occlusion, out-of-plane rotation, and out-of-view attributes on the OTB-2015 datasets, respectively. For sporting events, our framework presents much better performance and greater robustness than its competitors.
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http://dx.doi.org/10.1109/TIP.2021.3060164DOI Listing
March 2021

Hexose transporter CsSWEET7a in cucumber mediates phloem unloading in companion cells for fruit development.

Plant Physiol 2021 Feb 5. Epub 2021 Feb 5.

Beijing Key Laboratory of Growth and Developmental Regulation for Protected Vegetable Crops, College of Horticulture, China Agricultural University, Beijing 100193, China.

In the fleshy fruit of cucumbers (Cucumis sativus L.), the phloem flow is unloaded via an apoplasmic pathway, which requires protein carriers to export sugars derived from stachyose and raffinose into the apoplasm. However, transporter(s) involved in this process remain unidentified. Here, we report that a hexose transporter, CsSWEET7a (Sugar Will Eventually be Exported Transporter 7a), was highly expressed in cucumber sink tissues and localized to the plasma membrane in companion cells of the phloem. Its expression level increased gradually during fruit development. Down-regulation of CsSWEET7a by RNA interference (RNAi) resulted in smaller fruit size along with reduced soluble sugar levels and reduced allocation of 14C-labelled carbon to sink tissues. CsSWEET7a overexpression lines showed an opposite phenotype. Interestingly, genes encoding alkaline α-galactosidase (AGA) and sucrose synthase (SUS) were also differentially regulated in CsSWEET7a transgenic lines. Immunohistochemical analysis demonstrated that CsAGA2 co-localized with CsSWEET7a in companion cells, indicating cooperation between AGA and CsSWEET7a in fruit phloem unloading. Our findings indicated that CsSWEET7a is involved in sugar phloem unloading in cucumber fruit by removing hexoses from companion cells to the apoplasmic space to stimulate the raffinose family of oligosaccharides (RFOs) metabolism so that additional sugars can be unloaded to promote fruit growth. This study also provides a possible avenue towards improving fruit production in cucumber.
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http://dx.doi.org/10.1093/plphys/kiab046DOI Listing
February 2021

How Semiphysiological Population Pharmacokinetic Modeling Incorporating Active Hepatic Uptake Supports Phase II Dose Selection of RO7049389, A Novel Anti-Hepatitis B Virus Drug.

Clin Pharmacol Ther 2021 Apr 10;109(4):1081-1091. Epub 2021 Mar 10.

Pharmaceutical Sciences, Roche Pharma Research & Early Development, Roche Innovation Center Shanghai, Shanghai, China.

The pharmacokinetics (PK) of RO7049389, a new hepatitis B virus (HBV) core protein allosteric modulator of class I, and of its active metabolite M5 were studied in fasted and fed conditions after single and multiple once-a-day and twice-a-day doses in healthy subjects and patients with HBV. The nonlinearity of the pharmacokinetics, the large variability, the small sample size per dose arms, the higher plasma exposure in Asians, and the heterogeneity in patient baseline characteristics seen in phase I studies made the ethnic sensitivity assessment and the selection of the recommended phase II dose difficult. A population PK model, simultaneously modeling RO7049389 and M5, was developed to characterize the complex PK, quantify ethnicity (i.e., Asian vs. non-Asian) and gender effects on the PK of RO7049389 and M5, and infer the quantity of RO7049389 in liver relative to plasma. Exposures in the liver are of particular importance for dose selection since the liver is the site of action of the compound. The model described and reproduced the population PK profiles as well as the between-subject variability of RO7049389 and its metabolite. It could show that the PK is similar between healthy subjects and in HBV patients, once the ethnicity and gender effects are accounted for. The model predicts that, despite a large difference in the plasma exposure of RO7049389 between Asians and non-Asians, the exposure in the liver is comparable, allowing the use of the same dose to treat Asian and non-Asian patients. This model provides a valuable basis to develop this new anti-HBV drug and to define optimal dosing.
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http://dx.doi.org/10.1002/cpt.2184DOI Listing
April 2021

Further Evaluation of Coproporphyrins as Clinical Endogenous Markers for OATP1B.

J Clin Pharmacol 2021 Jan 18. Epub 2021 Jan 18.

Pharmaceutical Sciences, Roche Innovation Center Shanghai, Shanghai, China.

Coproporphyrins (CP-I and CP-III) in plasma are considered potential markers for assessing liver OATP1B activity and monitoring OATP1B-mediated drug-drug interactions (DDIs) in clinical settings. However, the effect of altered renal clearance (CL ) on CP-I and CP-III plasma exposure has rarely been examined. Therefore, the purpose of this study is to further evaluate CP-I and CP-III as clinical endogenous markers for OATP1B activity and to investigate the impact of CL on DDI assessments for the first time. In this study, eighteen healthy participants were recruited to receive RO7049389 (an inhibitor of OATP1B) 800 mg b.i.d. for 6 days and a single dose of pitavastatin (a probe drug of OATP1B) before and after RO7049389 treatment. Plasma concentrations of pitavastatin, CP-I and CP-III and the amounts of CP-I and CP-III excreted in urine were measured. Seventeen healthy participants completed the study. After multiple doses of RO7049389, the AUC of pitavastatin increased 1.95 [90% CI: 1.58-2.41]-fold, while the AUC of CP-I and CP-III increased 3.00 [90% CI: 2.35-3.82]- and 2.84 [90% CI: 2.22-3.65]-fold, respectively. Concurrently, the CL of CP-I decreased by 31% [90% CI: 23%-39%], and that of CP-III decreased by 70% [90% CI: 61%-77%]. In conclusion, CP-I and CP-III in plasma display the potential to be applied as endogenous markers for the evaluation of OATP1B inhibition in clinical trials. While renal transporters contribute significantly to the CL of CP-III, it would be better to investigate the impact of the CL on plasma exposure of CP-III during clinical DDI assessments. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1002/jcph.1817DOI Listing
January 2021

Matrix Information Geometry for Spectral-Based SPD Matrix Signal Detection with Dimensionality Reduction.

Entropy (Basel) 2020 Aug 20;22(9). Epub 2020 Aug 20.

College of Meteorology and Oceanography, National University of Defense Technology, Changsha 410073, China.

In this paper, a novel signal detector based on matrix information geometric dimensionality reduction (DR) is proposed, which is inspired from spectrogram processing. By short time Fourier transform (STFT), the received data are represented as a 2-D high-precision spectrogram, from which we can well judge whether the signal exists. Previous similar studies extracted insufficient information from these spectrograms, resulting in unsatisfactory detection performance especially for complex signal detection task at low signal-noise-ratio (SNR). To this end, we use a global descriptor to extract abundant features, then exploit the advantages of matrix information geometry technique by constructing the high-dimensional features as symmetric positive definite (SPD) matrices. In this case, our task for signal detection becomes a binary classification problem lying on an SPD manifold. Promoting the discrimination of heterogeneous samples through information geometric DR technique that is dedicated to SPD manifold, our proposed detector achieves satisfactory signal detection performance in low SNR cases using the K distribution simulation and the real-life sea clutter data, which can be widely used in the field of signal detection.
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http://dx.doi.org/10.3390/e22090914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7597166PMC
August 2020

Experimental and Computational Studies on Rh(I)-Catalyzed Reaction of Siloxyvinylcyclopropanes and Diazoesters.

J Am Chem Soc 2020 12 4;142(50):21032-21039. Epub 2020 Dec 4.

Beijing National Laboratory of Molecular Sciences (BNLMS), Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry, Peking University, Beijing 100871, China.

The Rh(I)-catalyzed reaction of siloxyvinylcyclopropanes and diazoesters leads to the formation of siloxyvinylcyclobutane and 1,4-diene derivatives. With [Rh(cod)Cl] as the catalyst, the formation of 1,4-diene was favored over the formation of siloxyvinylcyclobutane. By changing the catalyst to [Rh(cod)OTf], siloxyvinylcyclobutane derivatives are formed with excellent chemoselectivities and in moderate to good yields. The alkene products are also obtained as single configured isomers. A detailed mechanism for this transformation is proposed on the basis of mechanistic experiments and DFT calculations. The effect of catalysts on the chemoselectivity of these reactions is also examined computationally.
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http://dx.doi.org/10.1021/jacs.0c08089DOI Listing
December 2020

Facile Preparation of Wormlike Graphitic Carbon Nitride for Photocatalytic Degradation of Ustiloxin A.

Nanomaterials (Basel) 2020 Nov 14;10(11). Epub 2020 Nov 14.

State Key Laboratory of Biocatalysis and Enzyme Engineering, School of Life Sciences, Hubei University, Wuhan 430062, China.

Natural toxic contaminants have been recognized as threats to human health. Ustiloxins are the toxic secondary metabolites of fungus generated from rice false smut disease, which are harmful to animal/human reproduction and growth. However, there are rare researches on the control and reduction of ustiloxins through physical, chemical and biological ways. Herein, we demonstrated that photocatalysis of semiconductor nanomaterials could be as a potential way to degrade or mitigate the contamination of ustiloxin A. A kind of wormlike graphitic carbon nitride (g-CN) was facilely prepared from modified dicyandiamide precursor via pyrolysis method and characterized by X-ray diffraction, high-resolution transmission electron microscope and X-ray photoelectron spectroscopy etc. It was found that g-CN from modified dicyandiamide precursor showed better activity for ustiloxin A degradation under visible light irradiation than that of pristine g-CN. This was ascribed to the lager specific surface area, more uniform microstructure, better photogenerated charges separation and transformation of wormlike g-CN compared with pristine g-CN. Most important, the structure of degradation intermediates and the possible pathway were proposed based on the results of high-performance liquid chromatography-mass spectrometry after 80 min photoreaction treatment. Our findings may provide a green, efficient way for ustiloxins mitigation and useful information for future study.
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http://dx.doi.org/10.3390/nano10112256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7698057PMC
November 2020

What drives the dynamics of HBV RNA during treatment?

J Viral Hepat 2021 Feb 2;28(2):383-392. Epub 2020 Nov 2.

Université de Paris, INSERM, IAME, Paris, France.

Hepatitis B virus RNA (HBV RNA)-containing particles are encapsidated pre-genomic RNA (pgRNA) detectable in chronically infected patients in addition to virions (HBV DNA) that have been suggested as a marker of the treatment efficacy. This makes promising the use of core protein allosteric modulators, such as RG7907, which disrupt the nucleocapsid assembly and profoundly reduce HBV RNA. Here, we developed a multiscale model of HBV extending the standard viral dynamic models to analyse the kinetics of HBV DNA and HBV RNA in 35 patients treated with RG7907 for 28 days. We compare the predictions with those obtained in patients treated with the nucleotide analog tenofovir. RG7907 blocked 99.3% of pgRNA encapsidation (range: 92.1%-99.9%) which led to a decline of both HBV DNA and HBV RNA. As a consequence of its mode of action, the first phase of decline of HBV RNA was rapid, uncovering the clearance of viral particles with half-life of 45 min. In contrast, HBV DNA decline was predicted to be less rapid, due to the continuous secretion of already formed viral capsids (t  = 17 ± 6 h). After few days, both markers declined at the same rate, which was attributed to the loss of infected cells (t  ≅ 6 ± 0.8 days). By blocking efficiently RNA reverse transcription but not its encapsidation, nucleotide analog in contrast was predicted to lead to a transient accumulation of HBV RNA both intracellularly and extracellularly. The model brings a conceptual framework for understanding the differences between HBV DNA and HBV RNA dynamics. Integration of HBV RNA in viral dynamic models may be helpful to better quantify the treatment effect, especially in viral-suppressed patients where HBV DNA is no longer detectable.
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http://dx.doi.org/10.1111/jvh.13425DOI Listing
February 2021

A Five-in-One First-in-Human Study To Assess Safety, Tolerability, and Pharmacokinetics of RO7049389, an Inhibitor of Hepatitis B Virus Capsid Assembly, after Single and Multiple Ascending Doses in Healthy Participants.

Antimicrob Agents Chemother 2020 10 20;64(11). Epub 2020 Oct 20.

Pharmaceutical Sciences, Roche Innovation Center Shanghai, Shanghai, China

RO7049389, an inhibitor of hepatitis B virus (HBV) capsid assembly, is being developed for the treatment of patients with chronic HBV infection. The objectives of this first-in-human study are to assess the safety, tolerability, pharmacokinetics (PK), food effect, inhibitory effect on CYP3A, and effect on QT of RO7049389 in healthy participants. Five components, single-ascending-dose (SAD) cohorts, multiple-ascending-dose (MAD) cohorts, food effect assessment, drug-drug interaction assessment, and concentration-QT analysis were integrated in one study (five-in-one). Participants randomly received a single dose of 150 to 2,500 mg RO7049389 or placebo in SAD cohorts ( = 41), or multiple doses of 200 to 800 mg RO7049389 or placebo in MAD cohorts ( = 42). A single doses of 450 mg RO7049389 was administered under fasted and fed condition. The microdose of midazolam was administered before and after multiple dosing of RO7049389. Safety and tolerability were monitored throughout the study. Serial blood and urine samples were collected for the PK analysis. RO7049389 was safe and well tolerated in healthy participants. Absorption and elimination of RO7049389 occurred rapidly in plasma with minimal recovery in urine. Greater than dose-proportional increases in plasma exposure were observed. Exposure of RO7049389 (450 mg) increased by ∼2-fold when administered with a high-fat meal. The inhibition effect of RO7049389 on CYP3A was weak (<20%). No effect on QT interval was observed at up to a single dose of 2,500 mg. RO7049389 displayed a favorable safety, tolerability and PK profile suitable for further clinical development. (This trial was registered at ClinicalTrials.gov with the identifier NCT02952924.).
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http://dx.doi.org/10.1128/AAC.01323-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7577148PMC
October 2020

Encapsulation of tangeretin in PVA/PAA crosslinking electrospun fibers by emulsion-electrospinning: Morphology characterization, slow-release, and antioxidant activity assessment.

Food Chem 2021 Feb 4;337:127763. Epub 2020 Aug 4.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Environment Correlative Dietology, Huazhong Agricultural University, Ministry of Education, Wuhan 430070, China. Electronic address:

In this work, water-resistant poly (vinyl alcohol) (PVA)/poly (acrylic acid) (PAA) electrospun fibers encapsulating tangeretin (Tan) were fabricated by emulsion-electrospinning. To optimize the electrospinning condition, the size and morphology of electrospun fibers were characterized by dynamic light scattering (DLS), optical light microscope, fluorescence microscopy, and scanning electron microscopy (SEM), respectively. The optimized initial concentration of PVA/PAA was 10% (w/w) with a mass ratio of 3:7. The time and temperature of optimized thermal crosslinking treatment were 2 h and 145 °C, respectively. The results of XRD and SEM showed that the Tan was successfully incorporated into smooth PVA/PAA electrospun fibers and those fibers possessed nano-diameter size and high porosity. The encapsulation of Tan had no significant impact on the antioxidant activity of PVA/PAA/Tan crosslinking electrospun fibers. The in vitro release test showed the PVA/PAA/Tan crosslinking electrospun fibers achieved durable release profiles and lower burst release rates than that from the pure Tan emulsion. Based on these results, it is concluded that PVA/PAA/Tan crosslinking electrospun fibers prepared by emulsion-electrospinning serve as a promising technique in the fields of water-insoluble drug delivery and slow-release.
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http://dx.doi.org/10.1016/j.foodchem.2020.127763DOI Listing
February 2021

The influence of seasonal factors on the incidence of peritoneal dialysis-associated peritonitis.

Ren Fail 2020 Nov;42(1):807-817

Department of Nephrology, the Second Affiliated Hospital of Soochow University, Suzhou, P.R. China.

Objectives: To investigate the effects of climatic variables on peritoneal dialysis-associated peritonitis (PDAP) among patients receiving PD, such as seasonal variations in temperature and humidity.

Methods: A retrospective analysis was performed on PD patients, from 1 January 2011, to 31 December 2019. We evaluated the influence of seasonal factors on peritonitis rates and outcomes.

Results: Over the 9-year study period, 667 peritonitis episodes occurred, in 401 PD patients. Diarrhea-associated peritonitis occurred more frequently in summer compared with other seasons. Eating raw and cold food was identified as the primary cause of peritonitis in the summer. More peritonitis episodes occurred during summer. The peritonitis rate associated with gram-negative bacteria ( = 0.050) during summer was higher than those in all other seasons. The gram-negative bacterial peritonitis rate was positively correlated with monthly mean temperature ( = 0.504,  < 0.01) and humidity ( = 0.561,  < 0.01). A similar trend was observed for Enterobacterial peritonitis (temperature:  = 0.518,  < 0.01; humidity:  = 0.456,  = 0.001). Logistic regression analysis showed that summer was a risk factor for peritonitis ( = 0.041). Peritonitis prognosis during summer was significantly worse than those for all other seasons ( = 0.037).

Conclusions: Seasonal variations exist in the incidence of dialysis-associated peritonitis, with peak incidents caused by gram-negative bacteria in the summer. High average temperature and humidity are associated with significant increases in the gram-negative bacteria and Enterobacterial peritonitis rates. Peritonitis prognosis during summer is worse.
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http://dx.doi.org/10.1080/0886022X.2020.1804401DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7472476PMC
November 2020

Engineering Expression Cassette of for Efficient Production of Poly-γ-Glutamic Acids With Specific Molecular Weights in .

Front Bioeng Biotechnol 2020 9;8:728. Epub 2020 Jul 9.

State Key Laboratory of Biocatalysis and Enzyme Engineering, Environmental Microbial Technology Center of Hubei Province, College of Life Science, Hubei University, Wuhan, China.

Poly-γ-glutamic acid (γ-PGA) is an emerging biopolymer with various applications and γ-PGAs with different molecular weights exhibit distinctive properties. However, studies on the controllable molecular weights of biopolymers are limited. The purpose of this study is to achieve production of γ-PGAs with a wide range of molecular weights through manipulating the expression of γ-PGA depolymerase (PgdS) in WX-02. Firstly, the expression and secretion of PgdS were regulated through engineering its expression elements (four promoters and eight signal peptides), which generated γ-PGAs with molecular weights ranging from 6.82 × 10 to 1.78 × 10 Da. Subsequently, through combination of promoters with signal peptides, the production of γ-PGAs with a specific molecular weight could be efficiently obtained. Interestingly, the γ-PGA yield increased with the reduced molecular weight in flask cultures (Pearson correlation coefficient of -0.968, < 0.01). Finally, in batch fermentation, the highest yield of γ-PGA with a weight-average molecular weight of 7.80 × 10 Da reached 39.13 g/L under glutamate-free medium. Collectively, we developed an efficient strategy for one-step production of γ-PGAs with specific molecular weights, which have potential application for industrial production of desirable γ-PGAs.
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http://dx.doi.org/10.3389/fbioe.2020.00728DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381323PMC
July 2020

A Rapid LC-MS-MS Method for the Quantitation of Antiepileptic Drugs in Urine.

J Anal Toxicol 2020 Oct;44(7):688-696

Research and Development Department, Premier Biotech, 723 Kasota Ave SE, Minneapolis, MN 55414, USA.

Epilepsy is a common neurologic disease that requires treatment with one or more medications. Due to the polypharmaceutical treatments, potential side effects, and drug-drug interactions associated with these medications, therapeutic drug monitoring is important. Therapeutic drug monitoring is typically performed in blood due to established clinical ranges. While blood provides the benefit of determining clinical ranges, urine requires a less invasive collection method, which is attractive for medication monitoring. As urine does not typically have established clinical ranges, it has not become a preferred specimen for monitoring medication adherence. Thus, large urine clinical data sets are rarely published, making method development that addresses reasonable concentration ranges difficult. An initial method developed and validated in-house utilized a universal analytical range of 50-5,000 ng/mL for all antiepileptic drugs and metabolites of interest in this work, namely carbamazepine, carbamazepine-10,11-epoxide, eslicarbazepine, lamotrigine, levetiracetam, oxcarbazepine, phenytoin, 4-hydroxyphenytoin, and topiramate. This upper limit of the analytical range was too low leading to a repeat rate of 11.59% due to concentrations >5,000 ng/mL. Therefore, a new, fast liquid chromatography-tandem mass spectrometry (LC-MS-MS) method with a run time under 4 minutes was developed and validated for the simultaneous quantification of the previously mentioned nine antiepileptic drugs and their metabolites. Urine samples were prepared by solid-phase extraction and analyzed using a Phenomenex Phenyl-Hexyl column with an Agilent 6460 LC-MS-MS instrument system. During method development and validation, the analytical range was optimized for each drug to reduce repeat analysis due to concentrations above the linear range and for carryover. This reduced the average daily repeat rate for antiepileptic testing from 11.59% to 4.82%. After validation, this method was used to test and analyze patient specimens over the course of approximately one year. The resulting concentration data were curated to eliminate specimens that could indicate an individual was noncompliant with their therapy (i.e., positive for illicit drugs) and yielded between 20 and 1,700 concentration points from the patient specimens, depending on the analyte. The resulting raw quantitative urine data set is presented as preliminary reference ranges to assist with interpreting urine drug concentrations for the nine aforementioned antiepileptic medications and metabolites.
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http://dx.doi.org/10.1093/jat/bkaa095DOI Listing
October 2020

Combined nucleic acid assays for diagnosis of A19 vaccine-caused human brucellosis.

Transbound Emerg Dis 2020 Jun 16. Epub 2020 Jun 16.

Key Laboratory of Livestock Infectious Diseases in Northeast China, Ministry of Education, Shenyang Agricultural University, Shenyang, P. R. China.

Brucellosis is a common zoonotic disease caused by Brucella and is an epidemic worldwide. Currently, the most effective way to prevent and control the disease in animals is to use live, attenuated vaccines A19 strain. In China, the live attenuated Brucella abortus vaccine is widely used in animal immunization. To detect and confirm which vaccine strain caused the infection, we developed a new method to distinguish A19 strain from non-A19 strains. By comparing the genomic sequences of A19 and wild strain 2,308, we identified signature sequences that are unique to A19. A PCR assay for specific A19 identification was developed based on the genetic marker ABC transporter permease gene. Samples from the outbreak patients were then analysed using the universal quantitative PCR and A19-specific PCR assay, and the A19 strain was successfully identified in them, providing pathogenic evidence of the vaccine-derived infection outbreak. This combined A19-specific differential diagnosis method can provide a means to distinguish between animal vaccine immunization, natural infection and human infection by the vaccine strain. This strategy also has applications in diagnosis, epidemiology and surveillance of A19-related immunizations or infections.
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http://dx.doi.org/10.1111/tbed.13685DOI Listing
June 2020

Facile in situ synthesis of silver nanoparticles on tannic acid/zein electrospun membranes and their antibacterial, catalytic and antioxidant activities.

Food Chem 2020 Nov 2;330:127172. Epub 2020 Jun 2.

College of Food Science and Technology, Huazhong Agricultural University, Wuhan 430070, China. Electronic address:

This study demonstrates the development of biocompatible Ag nanoparticles/Tannic acid/Zein electrospun membranes with synergistic antibacterial, catalytic and antioxidant activity. The optimal spinning concentration of zein was 32 wt%. The prepared zein electrospun membranes were immersed into tannic acid (TA) solution to investigate the effects of TA concentrations, pH, temperature and time on the loading amount of TA. Then, the TA/Zein electrospun membranes were immersed into a silver nitrate solution to reduce the AgNPs in situ. The morphology of the electrospun membranes was characterized by scanning electron microscopy (SEM). UV-visible spectrophotometer, Fourier-transform infrared spectroscopy (FT-IR) and X-ray diffraction (XRD) were used to carry out the loading amount of TA and Ag nanoparticles (AgNPs). Finally, the antioxidant, antibacterial and catalytic activity of TA/Zein and AgNPs/TA/Zein electrospun membranes were studied. It was found that the AgNPs/TA/Zein electrospun membranes with different TA concentrations have certain antibacterial, antioxidation and catalytic ability, which may be of interest for the development of active packaging that could extend the shelf life of perishable foods.
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http://dx.doi.org/10.1016/j.foodchem.2020.127172DOI Listing
November 2020

Performance of Two Fentanyl Immunoassays against a Liquid Chromatography-Tandem Mass Spectrometry Method.

J Anal Toxicol 2021 Feb;45(2):117-123

Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania 3400 Spruce Street, Philadelphia, PA 19104, USA.

Rapid and automated fentanyl screening assays are in need due to the prevalence of fentanyl abuse. In the present study, we evaluated the clinical performance of two FDA-cleared automated fentanyl immunoassays, the Immunalysis SEFRIA fentanyl assay and the ARK fentanyl assay. Liquid chromatography-tandem mass spectrometry (LC-MS-MS) was used as a gold standard. Two groups of urine specimens were tested, including 225 specimens from patients presenting to the emergency department (ED) for whom urine drugs of abuse screens were ordered and 57 specimens from patients in chronic pain management programs. The SEFRIA assay generated higher assay imprecision than ARK assay (intraday CV%, 7.15 vs. 4.7%; interday CV%, 6.6 vs. 5.3%). Clinical sensitivity and specificity for detection of fentanyl exposure were 100 and 96% for the ARK assay and 95 and 80% for the SEFRIA assay. An 'auto-repeating' issue was observed for some validation specimens flagged with high absorbance values (OD > 3.0), generating false repeat results. The frequency of auto-repeating was lower in the ARK assay than SEFRIA (0.7 vs. 15.5%). Auto-repeating occurred for only previously frozen specimens in the ARK assay, but 9% of fresh specimens were also flagged and repeated in the SEFRIA assay. Positive predictive value (PPV) of the ARK assay was 73% in the ED population and 67% in the non-ED populations. The concentrations of fentanyl and norfentanyl were higher in specimens from ED patients than patients from pain management programs. High prevalence of morphine, methamphetamine, benzoylecgonine and 6-MAM was observed in specimens positive for fentanyl in both populations.
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http://dx.doi.org/10.1093/jat/bkaa053DOI Listing
February 2021

Evaluation of the Pharmacokinetics, Pharmacodynamics, and Safety of a Single Dose of Emicizumab in Healthy Chinese Subjects.

Clin Pharmacol Drug Dev 2021 Jan 20;10(1):30-38. Epub 2020 May 20.

F. Hoffmann-La Roche AG, Basel, Switzerland.

This phase 1, open-label, single-center study evaluated the pharmacokinetics (PK), pharmacodynamics, safety, and tolerability of single-dose emicizumab in healthy Chinese males. Overall, 16 subjects received a single subcutaneous dose of 1-mg/kg emicizumab. Blood samples were obtained before dosing on day 1 and at regular intervals over 16 weeks after dosing for PK evaluation. A single 1-mg/kg subcutaneous dose of emicizumab was safe and well tolerated in healthy Chinese male subjects in the study. Mean (± standard deviation) area under the concentration-time curve from time 0 to infinity and maximum concentration were 287 ± 74.2 μg⋅d/mL and 7.11 ± 1.77 μg/mL, respectively, with a terminal half-life of 26.7 (±4.3) days. Emicizumab administration did not show significant impact on pharmacodynamic markers tested, which mostly remained stable throughout the study. One subject tested positive for antidrug antibody, with no impact on his PK or safety profile. Compared with results from healthy Japanese and Caucasian subjects receiving the same dose in previous clinical trials, the current results further indicated the absence of difference of emicizumab PK profile across Chinese, Japanese, and Caucasian subjects, validating the use of similar therapeutic doses in Asian and non-Asian populations.
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http://dx.doi.org/10.1002/cpdd.805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7818492PMC
January 2021

Outcomes of occipitocervical fixation using a spinous process screw in C2 as a third anchor point for occipitocervical fixation: a case presentation.

BMC Musculoskelet Disord 2020 May 16;21(1):307. Epub 2020 May 16.

Department of Orthopedics, Ningbo NO.6 Hospital, 1059 Zhongsandong Road, Ningbo, Zhejiang, 315040, People's Republic of China.

Background: Posterior occipitocervical fixation and fusion are often required to address occipitocervical instability. Safe, stable internal fixation with screws is vital for the success of such surgery. Thus, poor selection of an internal fixation technique may cause fixation and fusion failure, possibly leading to neurovascular injury. Hence, in certain cases, such as in patients with severe instability of an occipitocervical deformity or osteoporosis, we hypothesized that having a third anchor point (a screw in C2) could enhance the stability of the occipitocervical fixation.

Case Presentation: A 31-year-old man with occipitocervical deformity and spinal cord edema underwent a traditional occipitocervical fixation procedure but with the addition of a spinous process screw in C2 as a third anchor point. The procedure included posterior internal fixation and fusion. The occipitocervical fixation was completed by inserting occipital screws, bilateral C2 pedicle screws, C3 lateral mass screws, and a spinous process screw in C2 as a third anchor point. There were no neurovascular complications or incision-site infections. Postoperatively, radiography and computed tomography showed that the occipitocervical reduction and internal fixation had resulted in good spinal alignment, and magnetic resonance imaging showed no obvious spinal cord compression. At 4 months after the surgery, fusion was observed, and the occipitocervical screws remained well positioned. The patient continued to be monitored for 24 months postoperatively. At the 24-month follow-up visit, the muscle strength of the limbs was grade 5, and the patient's sensation function had improved over his preoperative condition.

Conclusions: Use of a C2 spinous process screw as a third anchor point may enhance the stability of occipitocervical fixation. Further biomechanical and clinical studies are needed to validate this result.
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http://dx.doi.org/10.1186/s12891-020-03258-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229638PMC
May 2020

Highly Enantioselective Synthesis of Indazoles with a C3-Quaternary Chiral Center Using CuH Catalysis.

J Am Chem Soc 2020 06 1;142(23):10550-10556. Epub 2020 Jun 1.

Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, United States.

C3-substituted 1-indazoles are useful and important substructures in many pharmaceuticals. Methods for direct C3-functionalization of indazoles are relatively rare, compared to reactions developed for the more nucleophilic N1 and N2 positions. Herein, we report a highly C3-selective allylation reaction of 1--(benzoyloxy)indazoles using CuH catalysis. A variety of C3-allyl 1-indazoles with quaternary stereocenters were efficiently prepared with high levels of enantioselectivity. Density functional theory (DFT) calculations were performed to explain the reactivity differences between indazole and indole electrophiles, the latter of which was used in our previously reported method. The calculations suggest that the indazole allylation reaction proceeds through an enantioselectivity-determining six-membered Zimmerman-Traxler-type transition state, rather than an oxidative addition/reductive elimination sequence, as we proposed in the case of indole alkylation. The enantioselectivity of the reaction is governed by both ligand-substrate steric interactions and steric repulsions involving the pseudoaxial substituent in the six-membered allylation transition state.
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http://dx.doi.org/10.1021/jacs.0c04286DOI Listing
June 2020

Decomposing loss aversion from gaze allocation and pupil dilation.

Proc Natl Acad Sci U S A 2020 05 8;117(21):11356-11363. Epub 2020 May 8.

Wharton Neuroscience Initiative, The Wharton School, University of Pennsylvania, Philadelphia, PA 19104;

Loss-averse decisions, in which one avoids losses at the expense of gains, are highly prevalent. However, the underlying mechanisms remain controversial. The prevailing account highlights a valuation bias that overweighs losses relative to gains, but an alternative view stresses a response bias to avoid choices involving potential losses. Here we couple a computational process model with eye-tracking and pupillometry to develop a physiologically grounded framework for the decision process leading to accepting or rejecting gambles with equal odds of winning and losing money. Overall, loss-averse decisions were accompanied by preferential gaze toward losses and increased pupil dilation for accepting gambles. Using our model, we found gaze allocation selectively indexed valuation bias, and pupil dilation selectively indexed response bias. Finally, we demonstrate that our computational model and physiological biomarkers can identify distinct types of loss-averse decision makers who would otherwise be indistinguishable using conventional approaches. Our study provides an integrative framework for the cognitive processes that drive loss-averse decisions and highlights the biological heterogeneity of loss aversion across individuals.
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http://dx.doi.org/10.1073/pnas.1919670117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7260957PMC
May 2020

Correlation between plasma proprotein convertase subtilisin/kexin type 9 and blood lipids in patients with newly diagnosed primary nephrotic syndrome.

Ren Fail 2020 Nov;42(1):405-412

Department of Nephrology, The Second Affiliated Hospital of Soochow University, Suzhou, China.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a major post-transcriptional regulator of low-density lipoprotein receptor degradation. Recently, PCSK9 was shown to be overexpressed by liver cells in rats with proteinuria. However, the levels of PCSK9 in newly diagnosed primary nephrotic syndrome (PNS) patients and correlations involving PCSK9 and blood lipids are not clearly understood. One hundred and sixteen patients who were newly diagnosed with PNS were enrolled in this study. Plasma PCSK9 levels in PNS patients were significantly higher than those in healthy controls [310.86 (250.87, 390.25) ng/ml vs 255.67 (202.26, 320.26) ng/ml,  = 0.002]. Plasma PCSK9 in PNS patients was positively correlated with total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) (γ = 0.246,  = 0.008, and  = 0.183,  = 0.049). When plasma PCSK9 was >267.60 ng/ml, the risk of developing hypercholesterolemia significantly increased in PNS patients (OR = 6.40, 95% CI 2.06-19.87,  = 0.001). When plasma PCSK9 was >255.05 ng/ml, the risk of developing higher levels of LDL-C significantly increased in PNS patients (OR = 3.83, 95%CI 1.25-11.68,  = 0.018). Plasma PCSK9 levels in newly diagnosed PNS patients were markedly increased, and elevated PCSK9 abundance was positively correlated with elevated serum TC and LDL-C levels, suggesting that PCSK9 may emerge as a novel therapeutic target in NS-associated hypercholesterolemia.
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http://dx.doi.org/10.1080/0886022X.2020.1756846DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241483PMC
November 2020

Nutritional Status and Clinical Outcomes in Children with Cancer on Admission to Intensive Care Units.

Nutr Cancer 2021 18;73(1):83-88. Epub 2020 Mar 18.

Hemotology & Oncology, Nursing Department, Shanghai Children's Medical Center affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China.

Malnutrition is prevalent among pediatric oncology patients admitted to the pediatric intensive care unit (PICU), which leads to unfavorable clinical outcomes. This was a secondary data analysis of the nutrition data of 160 pediatric oncology patients admitted to the PICU. Cox's regression (adjusted for sex, age, and pediatric critical illness score) and Chi-square were used to examine the association between nutritional status and outcomes. Most of the patients were diagnosed with leukemia and admitted to PICU for medical reasons. The prevalence of malnutrition was 11.3% according to weight-for-age z-score, 16.3% according to height-for-age z-score, 21.3% according to body mass index-for-age z-score, 14.4% according to weight-for-height z-score, 34.4% according to mid-upper arm circumference-for-age z-score. Anthropometrical parameters that predicted the duration of mechanical ventilation were weight-for-age (hazard ratio [HR], 2.727; 95% confidence interval [CI], 1.729-4.302); height-for-age (HR, 1.969; 95% CI, 1.440-2.693); weight-for-height (HR, 2.645; 95% CI, 1.575-4.441); and upper arm muscle area-for-age (HR, 2.098; 95% CI, 1.430-3.077). Length of PICU stay was predicted by weight-for-age (HR, 1.207; 95% CI, 1.014-1.436). Malnutrition is prevalent among pediatric oncology patients admitted to the PICU, which lead to unfavorable clinical outcomes. Comprehensive nutritional status assessment should be performed for these children.
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http://dx.doi.org/10.1080/01635581.2020.1742361DOI Listing
March 2020

Biochemical assays of TCA cycle and β-oxidation metabolites.

Methods Cell Biol 2020 21;155:83-120. Epub 2020 Jan 21.

Faculty of Medicine, Hebrew University of Jerusalem, Metabolic Laboratory, Department of Genetic & Metabolic Diseases, Hadassah Medical Center, Jerusalem, Israel.

This chapter focuses on the methods to measure unique metabolites, specific enzymes, and metabolic flux in fatty acid β-oxidation, and on biochemical assays of tricarboxylic acid (TCA) cycle enzymes and the pyruvate dehydrogenase complex. These assays play an important role in the diagnosis of genetic diseases, newborn screening, and in cancer and metabolism research. The rationale, protocol, pros and cons, and alternative methods are discussed. Nevertheless, each laboratory should adapt the preferred method optimizing sample preparation and assay conditions for linearity and a low signal-to-noise ratio. The reader is also referred to the additional literature citing methods and clinical descriptions of the various diseases.
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http://dx.doi.org/10.1016/bs.mcb.2019.11.021DOI Listing
December 2020

Effects of Ceria Nanoparticles and CeCl on Plant Growth, Biological and Physiological Parameters, and Nutritional Value of Soil Grown Common Bean (Phaseolus vulgaris).

Small 2020 05 16;16(21):e1907435. Epub 2020 Mar 16.

Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.

The release of metal ions may play an important role in toxicity of metal-based nanoparticles. In this report, a life cycle study is carried out in a greenhouse, to compare the effects of ceria nanoparticles (NPs) and Ce ions at 0, 50, 100, and 200 mg Ce kg on plant growth, biological and physiological parameters, and nutritional value of soil-grown common bean plants. Ceria NPs have a tendency to negatively affect photosynthesis, but the effect is not statistically significant. Ce ionic treatments at 50, 100, and 200 mg Ce kg result in increases of 1.25-, 0.66-, and 1.20-fold in stomatal conductance, respectively, relative to control plants. Both ceria NPs and Ce ions disturb the homeostasis of antioxidant defense system in the plants, but only 200 mg Ce kg ceria NPs significantly induce lipid peroxidation in the roots. Ceria NP treatments tend to reduced fresh weight and to increase mineral contents of the green pods, but have no effect on the organic nutrient contents. On the contrary, Ce ion treatments modify the organic compositions and thus alter the nutritional quality and flavor of the green pods. These results suggest that the two Ce forms may have different mechanisms on common bean plants.
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http://dx.doi.org/10.1002/smll.201907435DOI Listing
May 2020

Vecuronium- and Esmolol-Induced Pseudohypernatremia Due to Drug Interference With Ion-Selective Electrodes.

Crit Care Explor 2020 Jan 29;2(1):e0073. Epub 2020 Jan 29.

Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Objectives: We observed that patients treated with continuous vecuronium or esmolol infusions showed elevated plasma sodium measurements when measured by the routine chemistry analyzer as part of the basic metabolic panel (Vitros 5600; Ortho Clinical Diagnostics, Raritan, NJ), but not by blood gas analyzers (RAPIDLab 1265; Siemens, Tarrytown, NY). Both instruments use direct ion-selective electrode technology, albeit with different sodium ionophores (basic metabolic panel: methyl monensin, blood gas: glass). We questioned if the basic metabolic panel hypernatremia represents artefactual pseudohypernatremia.

Design: We added vecuronium bromide or esmolol hydrochloric acid to pooled plasma samples and compared sodium values measured by both methodologies. We queried sodium results from the electronic medical records of patients admitted at Children's Hospital of Philadelphia from 2016 to 2018 and received vecuronium and/or esmolol infusion treatment during their admissions.

Setting: PICU of a quaternary, free-standing children's hospital.

Patients: Children admitted to the hospital who received vecuronium and/or esmolol infusion.

Measurements And Main Results: Sodium was measured in pooled plasma samples by basic metabolic panel and blood gas methodologies after adding vecuronium bromide or esmolol hydrochloric acid, leading to a dose-response increase in basic metabolic panel sodium measurements. A repeated measures regression analysis of our electronic medical records showed that the vecuronium dose predicted the Δ sodium (basic metabolic panel-blood gas) sodium within 12 hours of the vecuronium administration ( < 0.0018). Esmolol showed a similar trend ( = 0.13). This occurred primarily in central line samples with continuous vecuronium or esmolol infusions.

Conclusions: Vecuronium and esmolol can falsely elevate direct ion-selective electrode sodium measurements on Vitros chemistry analyzers. Unexpectedly high sodium measurements in patients receiving vecuronium and/or esmolol infusions should be further investigated with an alternate sample type (i.e., peripheral blood) or measurement methodology (i.e., blood gas) to guide treatment decisions.
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http://dx.doi.org/10.1097/CCE.0000000000000073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7063907PMC
January 2020

Inverse Relationship between Plasma Tumor Necrosis Factor-Like Weak Inducer of Apoptosis and Carotid Intima-Media Thickness among Patients Undergoing Hemodialysis and Peritoneal Dialysis.

Cardiorenal Med 2020 3;10(3):137-144. Epub 2020 Mar 3.

The Second Affiliated Hospital of Soochow University, Suzhou, China,

Background/aims: This study aimed to investigate the level of soluble tumor necrosis factor-like weak inducer of apoptosis (sTWEAK) and its correlation with micro-inflammation and atherosclerosis in continuous ambulatory peritoneal dialysis (PD) patients.

Methods: This retrospective study involved 23 healthy subjects (control group), 23 hemodialysis (HD) patients (HD group) and 26 PD patients (PD group). Serum biochemical measurements and sTWEAK assessments were tested. The association between intima-media thickness (IMT) and sTWEAK concentrations was evaluated.

Results: The TWEAK level was lower in PD (155.16 ± 3.69 pg/mL, p < 0.001) and the HD group (150.16 ± 7.23 pg/mL, p < 0.001) than that in the control group (193.05 ± 5.36 pg/mL), with no significant difference between the PD group and the HD group. In the PD and HD groups, sTWEAK was significant negatively correlated with CPR, fibrinogen, and white blood cell (p < 0.05). Besides, compared to lower sTWEAK concentration end-stage renal disease (ESRD) patients (no >161.9 pg/mL), patients who had a higher level of sTWEAK (>161.9 pg/mL) had a lower IMT (0.97 ± 0.04 vs. 0.84 ± 0.03 cm, p = 0.029). After adjusted for sex, age, hypertension, diabetes, duration of dialysis, triglyceride, total cholesterol, low-density lipoprotein, and serum glucose, sTWEAK (B = -0.002, r = 0.015) and CRP (B = 0.022, r = 0.015) were independent risk factors for the IMT of ESRD patients.

Conclusion: Plasma TWEAK is inversely associated with carotid IMT among patients undergoing HD and PD.
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http://dx.doi.org/10.1159/000503811DOI Listing
March 2020

Developing a cadmium resistant rice genotype with OsHIPP29 locus for limiting cadmium accumulation in the paddy crop.

Chemosphere 2020 May 21;247:125958. Epub 2020 Jan 21.

Department of Biochemistry and Molecular Biology, College of Life Science, Nanjing Agricultural University, Nanjing, 210095, China. Electronic address:

Widespread contamination of agricultural soil with toxic metals such as cadmium (Cd) is a major threat to crop production and human health. Metallochaperones are a unique class of proteins that play pivotal roles in detoxifying metallic ions inside cells. In this study, we investigated the biological function of an uncharacterized metallochaperone termed OsHIPP29 in rice plants and showed that OsHIPP29 resides in the plasma membrane and nucleus and detoxifies excess Cd and Zn. OsHIPP29 was primarily expressed in shoots during the vegetative stage and in leaf sheath and spikelet at the flowering stage. It can be differentially induced by excess Cd, Zn, Cu, Fe and Mn. To identify the function of OsHIPP29 in mediating rice response to Cd stress, we examined a pair of OsHIPP29 mutants, RNAi lines and transgenic rice overexpressing OsHIPP29 (OX) under Cd stress. Both mutant and RNAi lines are sensitive to Cd in growth as reflected in decreased plant height and dry biomass. In contrast, the OX lines showed better growth under Cd exposure. Consistent with the phenotype, the OX lines accumulated less Cd in both root and shoot tissues, whereas OsHIPP29 knockout led to higher accumulation of Cd. These results point out that expression of OsHIPP29 is able to contribute to Cd detoxification by reducing Cd accumulation in rice plants. Our work highlights the significance of OsHIPP29-mediated reduced Cd in rice plants, with important implications for further developing genotypes that will minimize Cd accumulation in rice and environmental risks to human health.
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http://dx.doi.org/10.1016/j.chemosphere.2020.125958DOI Listing
May 2020