Publications by authors named "Lan Zhou"

385 Publications

Lateral femoral cutaneous neuropathy caused by prone positioning to treat COVID-19-associated acute respiratory distress syndrome.

Authors:
Lan Zhou Peter Siao

Muscle Nerve 2021 Feb 12. Epub 2021 Feb 12.

Department of Neurology, Boston Medical Center, Boston, MA, USA.

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http://dx.doi.org/10.1002/mus.27202DOI Listing
February 2021

Geostatistical modeling of positive-definite matrices: An application to diffusion tensor imaging.

Biometrics 2021 Feb 11. Epub 2021 Feb 11.

Virginia Commonwealth University, Richmond, Virginia.

Geostatistical modeling for continuous point-referenced data has extensively been applied to neuroimaging because it produces efficient and valid statistical inference. However, diffusion tensor imaging (DTI), a neuroimaging technique characterizing the brain's anatomical structure, produces a positive-definite (p.d.) matrix for each voxel. Currently, only a few geostatistical models for p.d. matrices have been proposed because introducing spatial dependence among p.d. matrices properly is challenging. In this paper, we use the spatial Wishart process, a spatial stochastic process (random field), where each p.d. matrix-variate random variable marginally follows a Wishart distribution, and spatial dependence between random matrices is induced by latent Gaussian processes. This process is valid on an uncountable collection of spatial locations and is almost-surely continuous, leading to a reasonable way of modeling spatial dependence. Motivated by a DTI data set of cocaine users, we propose a spatial matrix-variate regression model based on the spatial Wishart process. A problematic issue is that the spatial Wishart process has no closed-form density function. Hence, we propose an approximation method to obtain a feasible Cholesky decomposition model, which we show to be asymptotically equivalent to the spatial Wishart process model. A local likelihood approximation method is also applied to achieve fast computation. The simulation studies and real data application demonstrate that the Cholesky decomposition process model produces reliable inference and improved performance, compared to other methods.
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http://dx.doi.org/10.1111/biom.13445DOI Listing
February 2021

Long-Distance Entanglement Purification for Quantum Communication.

Phys Rev Lett 2021 Jan;126(1):010503

CAS Key Laboratory of Quantum Information, University of Science and Technology of China, Hefei 230026, People's Republic of China.

High-quality long-distance entanglement is essential for both quantum communication and scalable quantum networks. Entanglement purification is to distill high-quality entanglement from low-quality entanglement in a noisy environment and it plays a key role in quantum repeaters. The previous significant entanglement purification experiments require two pairs of low-quality entangled states and were demonstrated in tabletop. Here we propose and report a high-efficiency and long-distance entanglement purification using only one pair of hyperentangled state. We also demonstrate its practical application in entanglement-based quantum key distribution (QKD). One pair of polarization spatial-mode hyperentanglement was distributed over 11 km multicore fiber (noisy channel). After purification, the fidelity of polarization entanglement arises from 0.771 to 0.887 and the effective key rate in entanglement-based QKD increases from 0 to 0.332. The values of Clauser-Horne-Shimony-Holt inequality of polarization entanglement arises from 1.829 to 2.128. Moreover, by using one pair of hyperentanglement and deterministic controlled-NOT gates, the total purification efficiency can be estimated as 6.6×10^{3} times than the experiment using two pairs of entangled states with spontaneous parametric down-conversion sources. Our results offer the potential to be implemented as part of a full quantum repeater and large-scale quantum network.
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http://dx.doi.org/10.1103/PhysRevLett.126.010503DOI Listing
January 2021

Generation of a Bovine Serum Albumin-Diligand Complex for the Protection of Bioactive Quercetin and Suppression of Heme Toxicity.

Chem Res Toxicol 2021 Jan 19. Epub 2021 Jan 19.

Key Laboratory of Functional Small Organic Molecule, Ministry of Education; College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi China.

As an abundant protein in milk and blood serum, bovine serum albumin (BSA) contains various sites to bind a lot of bioactive components, generating BSA-monoligand complex. Demonstration of the interaction between BSA and bioactive components (such as heme, flavonoids) is important to develop effective carrier for the protection of bioactive ligands and to reduce cytotoxicity of heme. Herein, the bindings of BSA to quercetin and/or heme were investigated by multispectroscopic and molecular docking methods. The fluorescence of protein was significantly quenched by both quercetin and heme in a static mode (i.e., generation of BSA-ligand complex). Although quercetin had lower affinity to protein than heme, the interactions of both compounds with protein did locate in site I (i.e., subdomain IIA). BSA-diligand complex was successfully generated after the coaddition of quercetin and heme. The cytotoxicity of free heme to endothelial cells was reduced in the BSA-diligand complex relative to that of heme or BSA-monoligand complex, while the stability of bioactive quercetin was promoted in the complex relative to free flavonoid. The complex provided a better inhibition on the cytotoxicity of heme than BSA-monoligand complex, in which the copresence of quercetin played a vital role.
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http://dx.doi.org/10.1021/acs.chemrestox.0c00537DOI Listing
January 2021

Notch-Regulated Dendritic Cells Restrain Inflammation-Associated Colorectal Carcinogenesis.

Cancer Immunol Res 2021 Mar 13;9(3):348-361. Epub 2021 Jan 13.

Department of Pathology, Case Western Reserve University, Cleveland, Ohio.

Conventional dendritic cells (cDC) play a central role in T-cell antitumor responses. We studied the significance of Notch-regulated DC immune responses in a mouse model of colitis-associated colorectal cancer in which there is epithelial downregulation of Notch/Hes1 signaling. This defect phenocopies that caused by (GDP-mannose 4,6-dehydratase) mutation in human colorectal cancers. We found that, although wild-type immune cells restrained dysplasia progression and decreased the incidence of adenocarcinoma in chimeric mice, the immune system with Notch2 deleted in all blood lineages or in only DCs promoted inflammation-associated transformation. Notch2 signaling deficiency not only impaired cDC terminal differentiation, but also downregulated CCR7 expression, reduced DC migration, and suppressed antigen cross-presentation to CD8 T cells. Transfer of Notch-primed DCs restrained inflammation-associated dysplasia progression. Consistent with the mouse data, we observed a correlation between infiltrating cDC1 and Notch2 signaling in human colorectal cancers and found that -mutant colorectal cancers showed decreased CCR7 expression and suppressed cDC1 signature gene expression. Suppressed cDC1 gene signature expression in human colorectal cancer was associated with a poor prognosis. In summary, our study supports an important role for Notch2 signaling in cDC1-mediated antitumor immunity and indicates that Notch2-controlled DCs restrain inflammation-associated colon cancer development in mice.
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http://dx.doi.org/10.1158/2326-6066.CIR-20-0428DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925430PMC
March 2021

Effect of Organic Electrolyte on the Performance of Solid Electrolyte for Solid-Liquid Hybrid Lithium Batteries.

ACS Appl Mater Interfaces 2021 Jan 8;13(2):2685-2693. Epub 2021 Jan 8.

Department of Chemistry, Shanghai Key Laboratory of Molecular Catalysis and Innovative Materials, Collaborative Innovation Center of Chemistry for Energy Materials, Fudan University, Shanghai 200438, China.

The interface problem caused by the contact between the electrodes and the solid electrolyte was the main factor hindering the development of solid-state batteries. To enhance the electrode|solid electrolyte interface property, we designed a hybrid electrolyte, the combination of vol % LiAlTi(PO) (LATP) inorganic solid electrolyte and 1 - vol % liquid organic electrolyte (LE). In this work, the 1 - vol % LE was dropped between the electrode and the solid electrolyte, and it is found that the electrochemical performance of the LiFePO|Li solid-liquid hybrid battery is significantly improved. At the current density of 0.1 and 0.5 C, the LATP with 15% liquid organic electrolyte could deliver a specific capacity of 160.5 and 124.3 mAh g, respectively; moreover, the specific discharge capacity remained as high as 111 mAh g at 0.5 C after 100 cycles, indicating that the larger interface impedance was eliminated. The LE may have three functions: (1) forming a solid-liquid electrolyte interphase on the surface of the LATP particles to prevent further reduction of LATP, (2) wetting the electrode and solid electrolyte to reduce the interface resistance, and (3) improving interfacial Li-ion transport.
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http://dx.doi.org/10.1021/acsami.0c19671DOI Listing
January 2021

Quercetin Attenuated Myeloperoxidase-Dependent HOCl Generation and Endothelial Dysfunction in Diabetic Vasculature.

J Agric Food Chem 2021 Jan 4;69(1):404-413. Epub 2021 Jan 4.

MOE Key Laboratory of Functional Small Organic Molecule, College of Chemistry and Chemical Engineering, Jiangxi Normal University, Nanchang, Jiangxi 330022, China.

Myeloperoxidase (MPO)-dependent hypochlorous acid (HOCl) generation plays crucial roles in diabetic vascular complications. As a natural polyphenol, quercetin has antioxidant properties in various diabetic models. Herein, we investigated the therapeutic mechanism for quercetin on MPO-mediated HOCl generation and endothelial dysfunction in diabetic vasculature. In vitro, the presence of MPO could amplify high glucose-induced endothelial dysfunction which was significantly inhibited by the NADPH oxidase inhibitor, HOCl or HO scavengers, revealing the contribution of MPO/HO/HOCl to vascular endothelial injury. Furthermore, quercetin effectively inhibited MPO/high glucose-mediated HOCl generation and cytotoxicity to vascular endothelial cells. The inhibitive effect on MPO activity was related to the fact that quercetin reduced high glucose-induced HO generation in endothelial cells and directly acted as a competitive substrate for MPO, thus limiting MPO/HO-dependent HOCl production. Moreover, quercetin could attenuate HOCl-caused endothelial dysfunction in endothelial cells and isolated aortas. In vivo, dietary quercetin significantly inhibited aortic endothelial dysfunction in diabetic mice, while this compound simultaneously suppressed vascular MPO expression and activity. Therefore, it was demonstrated herein that quercetin inhibited endothelial injury in diabetic vasculature via suppression of MPO/high glucose-dependent HOCl formation.
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http://dx.doi.org/10.1021/acs.jafc.0c06335DOI Listing
January 2021

O-Fucose and Fringe-modified NOTCH1 Extracellular Domain Fragments as Decoys to Release Niche-lodged Hematopoietic Progenitor Cells.

Glycobiology 2020 Dec 22. Epub 2020 Dec 22.

Department of Pathology, Case Western Reserve University, Cleveland, OH 44106, USA.

Successful hematopoietic progenitor cell (HPC) transplant therapy is improved by mobilizing HPCs from the bone marrow niche in donors. Notch receptor-ligand interactions are known to retain HPCs in the bone marrow, and neutralizing antibodies against Notch ligands, JAG1 or DLL4, or NOTCH2 receptor potentiates HPC mobilization. Notch-ligand interactions are dependent on posttranslational modification of Notch receptors with O-fucose and are modulated by Fringe-mediated extension of O-fucose moieties. We previously reported that O-fucosylglycans on Notch are required for Notch receptor-ligand engagement controlling hematopoietic stem cell quiescence and retention in the marrow niche. Here we generated recombinant fragments of NOTCH1 or NOTCH2 extracellular domain carrying the core ligand binding regions (EGF11-13) either as unmodified forms or as O-fucosylglycan-modified forms. We found that the addition of O-fucose monosaccharide or the Fringe-extended forms of O-fucose to EGF11-13 showed substantial increases in binding to DLL4. Further, the O-fucose and Fringe-extended NOTCH1 EGF11-13 protein displayed much stronger binding to DLL4 than the NOTCH2 counterpart. When assessed in an in vitro 3D osteoblastic niche model, we showed that the Fringe-extended NOTCH1 EGF11-13 fragment effectively released lodged HPC cells with a higher potency than the NOTCH2 blocking antibody. We concluded that O-fucose and Fringe-modified NOTCH1 EGF11-13 protein can be utilized as effective decoys for stem cell niche localized ligands to potentiate HPC egress and improve HPC collection for hematopoietic cell therapy.
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http://dx.doi.org/10.1093/glycob/cwaa113DOI Listing
December 2020

Inflammatory cytokine depletion in severe coronavirus disease 2019 infectious pneumonia: A case report.

Medicine (Baltimore) 2020 Dec;99(49):e23449

Internal Medicine III (Nephrology & Endocrinology), Naval Medical Center of PLA, Second Military Medical University, Shanghai.

Rationale: Multiorgan/system injury was observed in severely infected coronavirus disease 2019 (COVID-19) patients, in addition to viral pneumonia. Recognizing and correcting the key and immediate dysfunctions may reduce mortality.

Patient Concerns: A 66-year-old previously healthy male patient was referred to the isolation ward in Guanggu Branch of Hubei Province Maternity and Childcare Hospital with a high fever and nonproductive cough for twenty days.

Diagnoses: Diagnosis of severe COVID-19 infectious pneumonia was established by travel history, clinical features, chest imaging, and a positive oropharyngeal swab specimen result for the severe acute respiratory syndrome coronavirus 2 RT-PCR assay.

Interventions: In addition to standard supportive care, combined inflammatory cytokine depletion therapy (double filtration plasma pheresis and tocilizumab) and convalescent plasma were administered.

Outcomes: The patient's homeostatic parameters (blood pressure, heart rate, spontaneous respiration, SPO2, and blood gas) recovered, along with the recovery on chest imaging. All the intravenous catheters were removed. Supportive care continued for several days, and the patient was transferred to a non-ICU isolation ward.

Lessons: It is not safe to draw causal conclusions between cytokine depletion and clinical manifestation improvement with only 1 case, but this is a potential research direction in facing the COVID-19 crisis.
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http://dx.doi.org/10.1097/MD.0000000000023449DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7717847PMC
December 2020

Bi Alloying into Rare Earth Double Perovskites Enhances Synthesizability and Visible Light Absorption.

ACS Comb Sci 2020 12 29;22(12):895-901. Epub 2020 Oct 29.

Joint Center for Artificial Photosynthesis, California Institute of Technology, Pasadena, California 91125, United States.

A high throughput combinatorial synthesis utilizing inkjet printing of precursor inks was used to rapidly evaluate Bi-alloying into double perovskite oxides for enhanced visible light absorption. The fast visual screening of photo image scans of the library plates identifies 4-metal oxide compositions displaying an increase in light absorption, which subsequent UV-vis spectroscopy indicates is due to bandgap reduction. Structural characterization by X-ray diffraction (XRD) and Raman spectroscopy demonstrates that the visually darker composition range contains Bi-alloyed SmMnNiO (double perovskite structure), of the form (Bi,Sm)MnNiO. Bi alloying not only increases the visible absorption but also facilitates crystallization of this structure at the relatively low annealing temperature of 615 °C. Investigation of additional seven combinations of a rare earth (RE) and a transition metal (TM) with Bi and Mn indicates that Bi-alloying on the RE site occurs with similar effect in the family of rare earth oxide double perovskites.
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http://dx.doi.org/10.1021/acscombsci.0c00177DOI Listing
December 2020

Detection of pathogens in ixodid ticks collected from animals and vegetation in five regions of Ukraine.

Ticks Tick Borne Dis 2021 01 4;12(1):101586. Epub 2020 Oct 4.

Department of Veterinary Pathobiology, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77845, USA.

The distribution and prevalence of zoonotic pathogens infecting ixodid ticks in Western Europe have been extensively examined. However, data on ticks and tick-borne pathogens in Eastern Europe, particularly Ukraine are scarce. The objective of the current study was, therefore, to investigate the prevalence of Anaplasma phagocytophilum, Anaplasmataceae, Rickettsia spp., Babesia spp., Bartonella spp., and Borrelia burgdorferi sensu lato in engorged and questing ixodid ticks collected from five administrative regions (oblasts) of Ukraine, namely Chernivtsi, Khmelnytskyi, Kyiv, Ternopil, and Vinnytsia. The ticks were collected from both wild and domestic animals and from vegetation. Of 524 ixodid ticks collected, 3, 99, and 422 ticks were identified as Ixodes hexagonus, Ixodes ricinus, and Dermacentor reticulatus, respectively. DNA samples individually extracted from 168 questing and 354 engorged adult ticks were subjected to pathogen-specific PCR analyses. The mean prevalence in I. ricinus and D. reticulatus were, respectively: 10 % (10/97) and 3 % (12/422) for A. phagocytophilum; 69 % (67/97) and 52 % (220/422) for members of the Anaplasmataceae family; 25 % (24/97) and 28 % (117/422) for Rickettsia spp.; 3 % (3/97) and 1 % (6/422) for Babesia spp.; and 9 % (9/97) and 5 % (20/422) for Bartonella spp. Overall, between the five cities, there was no significant difference in the prevalence of any of the pathogens for the respective ticks (p > 0.05). The prevalence of B. burgdorferi s. l. in the questing and engorged I. ricinus varied from 0 to 27 % and 14-44%, respectively, with no statistical significance identified between the five cities (p > 0.05). In addition to reporting the updated data for Kyiv and Ternopil, this study is the first to provide the prevalences of the tick-borne pathogens for Chernivtsi, Khmelnytskyi, and Vinnytsia. This investigation is also the first to detect Neoehrlichia mikurensis in ixodid ticks from Ukraine. These new data will be useful for medical and veterinary practitioners as well as public health officials when diagnosing infections and when implementing measures to combat tick-borne diseases in Ukraine.
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http://dx.doi.org/10.1016/j.ttbdis.2020.101586DOI Listing
January 2021

Association between the pri-miR-26a-1 rs7372209 C>T polymorphism and cancer susceptibility: multivariate analysis and trial sequential analysis.

Aging (Albany NY) 2020 Oct 14;12(19):19060-19072. Epub 2020 Oct 14.

Department of Stomatology, Department of Clinical Oncology, Hubei Key Laboratory of Embryonic Stem Cell Research, Taihe Hospital, Hubei University of Medicine, Shiyan 442000, China.

MiR-26 has been suggested to play a tumor-suppressive role in cancer development, which could be influenced by the mutate pri-miR-26ª-1. Molecular epidemiological studies have demonstrated some inconsistent associations between pri-miR-26ª-1 rs7372209 C>T polymorphism and cancer risk. We therefore performed this meta-analysis with multivariate statistic method to comprehensively evaluate the associations between rs7372209 C>T polymorphism and cancer risk. Eleven publications involving 6,709 patients and 6,514 controls were identified. Multivariate analysis indicated that the over-dominant genetic model was most likely. Pooled results indicated no significant association in the overall population (CC+TT vs. CT: OR=1.08, 95%CI=0.96-1.22, =0.20, =54.4%), as well as the subgroup analysis according to ethnicity, control source, tumor locations, and HWE status of controls. In addition, heterogeneity, accumulative, sensitivity analysis, publication bias and trial sequential analysis (TSA) were conducted to test the statistical power. Overall, our results indicated that the pri-miR-26a-1 rs7372209 C>T polymorphism may not be a potential risk for cancer development.
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http://dx.doi.org/10.18632/aging.103696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732283PMC
October 2020

Comparison of Surface-Enhanced Raman Scattering Properties of Serum and Urine for the Detection of Chronic Kidney Disease in Patients.

Appl Spectrosc 2020 Oct 29:3702820966322. Epub 2020 Oct 29.

Department of Urologic Sciences, University of British Columbia, Vancouver, Canada.

Chronic kidney disease (CKD) affects more than 10% of the global population and is associated with significant morbidity and mortality. In most cases, this disease is developed silently, and it can progress to the end-stage renal failure. Therefore, early detection becomes critical for initiating effective interventions. Routine diagnosis of CKD requires both blood test and urinalyses in a clinical laboratory, which are time-consuming and have low sensitivity and specificity. Surface-enhanced Raman scattering (SERS) is an emerging method for rapidly assessing kidney function or injury. This study was designed to compare the differences between the SERS properties of the serum and urine for easy and simple detection of CKD. Enrolled for this study were 126 CKD patients (Stages 2-5) and 97 healthy individuals. SERS spectra of both the serum and urine samples were acquired using a Raman spectrometer (785 nm excitation). The correlation of chemical parameters of kidney function with the spectra was examined using prinicpal component analysis (PCA) combined with linear discriminant analysis (LDA) and partial least squares (PLS) analysis. Here, we showed that CKD was discriminated from non-CKD controls using PCA-LDA with a sensitivity of 74.6% and a specificity of 93.8% for the serum spectra, and 78.0% and 86.0 % for the urine spectra. The integration area under the receiver operating characteristic curve was 0.937 ± 0.015 ( < 0.0001) for the serum and 0.886 ± 0.025 ( < 0.0001) for the urine. The different stages of CKD were separated with the accuracy of 78.0% and 75.4% by the serum and urine spectra, respectively. PLS prediction (R) of the serum spectra was 0.8540 for the serum urea ( < 0.001), 0.8536 for the serum creatinine ( < 0.001), 0.7500 for the estimated glomerular filtration rate (eGFR) ( < 0.001), whereas the prediction (R) of urine spectra was 0.7335 for the urine urea ( < 0.001), 0.7901 for the urine creatinine ( < 0.001), 0.4644 for the eGFR ( < 0.001) and 0.6579 for the urine microalbumin ( < 0.001). In conclusion, the accuracy of associations between SERS findings of the serum and urine samples with clinical conclusions of CKD diagnosis in this limited number of patients is similar, suggesting that SERS may be used as a rapid and easy-to-use method for early screening of CKD, which however needs further evaluation in a large cohort study.
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http://dx.doi.org/10.1177/0003702820966322DOI Listing
October 2020

Electrospinning Synthesis of Carbon-Supported PtMn Intermetallic Nanocrystals and Electrocatalytic Performance towards Oxygen Reduction Reaction.

Nanomaterials (Basel) 2020 Sep 22;10(9). Epub 2020 Sep 22.

Shandong Provincial Key Laboratory of Chemical Energy Storage and Novel Cell Technology, School of Chemistry and Chemical Engineering, Liaocheng University, Liaocheng 252059, China.

To realize the large-scale application of fuel cells, it is still a great challenge to improve the performance and reduce the cost of cathode catalysts towards oxygen reduction reaction (ORR). In this work, carbon-supported ordered PtMn intermetallic catalysts were prepared by thermal annealing electrospun polyacrylonitrile nanofibers containing Platinum(II) acetylacetonate/ Manganese(III) acetylacetonate. Compared with its counterparts, the ordered PtMn intermetallic obtained at 950 °C exhibits a more positive half-potential and higher kinetic current density during the ORR process. Benefiting from their defined stoichiometry and crystal structure, the Mn atoms in PtMn intermetallic can modulate well the geometric and electronic structure of surface Pt atoms, endowing PtMn catalyst with an enhanced ORR catalytic activity. Moreover, it also has a better catalytic stability and methanol tolerance than commercial Pt/C catalyst. Our study provides a new strategy to fabricate a highly active and durable PtMn intermetallic electrocatalyst towards ORR.
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http://dx.doi.org/10.3390/nano10091893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7559926PMC
September 2020

Classification of estrogenic compounds by coupling high content analysis and machine learning algorithms.

PLoS Comput Biol 2020 09 24;16(9):e1008191. Epub 2020 Sep 24.

Texas A&M Energy Institute, Texas A&M University, College Station, TX, United States of America.

Environmental toxicants affect human health in various ways. Of the thousands of chemicals present in the environment, those with adverse effects on the endocrine system are referred to as endocrine-disrupting chemicals (EDCs). Here, we focused on a subclass of EDCs that impacts the estrogen receptor (ER), a pivotal transcriptional regulator in health and disease. Estrogenic activity of compounds can be measured by many in vitro or cell-based high throughput assays that record various endpoints from large pools of cells, and increasingly at the single-cell level. To simultaneously capture multiple mechanistic ER endpoints in individual cells that are affected by EDCs, we previously developed a sensitive high throughput/high content imaging assay that is based upon a stable cell line harboring a visible multicopy ER responsive transcription unit and expressing a green fluorescent protein (GFP) fusion of ER. High content analysis generates voluminous multiplex data comprised of minable features that describe numerous mechanistic endpoints. In this study, we present a machine learning pipeline for rapid, accurate, and sensitive assessment of the endocrine-disrupting potential of benchmark chemicals based on data generated from high content analysis. The multidimensional imaging data was used to train a classification model to ultimately predict the impact of unknown compounds on the ER, either as agonists or antagonists. To this end, both linear logistic regression and nonlinear Random Forest classifiers were benchmarked and evaluated for predicting the estrogenic activity of unknown compounds. Furthermore, through feature selection, data visualization, and model discrimination, the most informative features were identified for the classification of ER agonists/antagonists. The results of this data-driven study showed that highly accurate and generalized classification models with a minimum number of features can be constructed without loss of generality, where these machine learning models serve as a means for rapid mechanistic/phenotypic evaluation of the estrogenic potential of many chemicals.
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http://dx.doi.org/10.1371/journal.pcbi.1008191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538107PMC
September 2020

Liver X receptor β is required for the survival of single-positive thymocytes by regulating IL-7Rα expression.

Cell Mol Immunol 2020 Sep 22. Epub 2020 Sep 22.

Institute of Immunology, College of Basic Medical Sciences, Third Military Medical University, Chongqing, 400038, China.

Liver X receptors (LXRs) are known as key transcription factors in lipid metabolism and have been reported to play an important role in T-cell proliferation. However, whether LXRs play a role in thymocyte development remains largely unknown. Here, we demonstrated that LXRβ deficiency caused a reduction in single-positive (SP) thymocytes, whereas the transitions from the double-negative to SP stage were normal. Meanwhile, LXRβ-null SP thymocytes exhibited increased apoptosis and impairment of the IL-7Rα-Bcl2 axis. In addition, the LXR agonist T0901317 promoted the survival of SP thymocytes with enhanced IL-7Rα expression in wild-type mice but not in LXRβ-deficient mice. Mechanistically, LXRβ positively regulated the expression of IL-7Rα via direct binding to the Il7r allele in SP thymocytes, and forced expression of IL-7Rα or Bcl2 restored the survival of LXRβ-defective SP thymocytes. Thus, our results indicate that LXRβ functions as an important transcription factor upstream of IL-7Rα to promote the survival of SP thymocytes.
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http://dx.doi.org/10.1038/s41423-020-00546-yDOI Listing
September 2020

Comment on COVID-19 in patients with myasthenia gravis: Author response.

Muscle Nerve 2020 12 21;62(6):E87-E88. Epub 2020 Sep 21.

Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, USA.

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http://dx.doi.org/10.1002/mus.27062DOI Listing
December 2020

Clinical course and risk factors for recurrence of positive SARS-CoV-2 RNA: a retrospective cohort study from Wuhan, China.

Aging (Albany NY) 2020 Sep 10;12(17):16675-16689. Epub 2020 Sep 10.

Department of Cardiothoracic Surgery, Naval Medical Center of PLA, Shanghai 200052, People’s Republic of China.

The coronavirus disease 2019 (COVID-19) pandemic is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The objective of this study was to determine the clinical course and risk factors for patients showing recurrent SARS-CoV-2 RNA positivity. A total of 1087 COVID-19 patients confirmed by RT-PCR from February 24, 2020 to March 31, 2020 were retrospectively enrolled. Advanced age was significantly associated with mortality. In addition, 81 (7.6%) of the discharged patients tested positive for SARS-CoV-2 RNA during the isolation period. For patients with recurrent RT-PCR positivity, the median duration from illness onset to recurrence was 50 days. Multivariate regression analysis identified elevated serum IL-6, increased lymphocyte counts and CT imaging features of lung consolidation during hospitalization as the independent risk factors of recurrence. We hypothesized that the balance between immune response and virus toxicity may be the underlying mechanism of this phenomenon. For patients with a high risk of recurrence, a prolonged observation and additional preventative measures should be implemented for at least 50 days after illness onset to prevent future outbreaks.
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http://dx.doi.org/10.18632/aging.103795DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521537PMC
September 2020

Prevalence and risk factors of low health literacy in residents of Anhui province: A cross-sectional survey.

Authors:
Chao Wang Lan Zhou

Medicine (Baltimore) 2020 Aug;99(34):e20547

Department of Traditional Chinese Medicine, The First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

This survey aimed to evaluate the prevalence of low health literacy and correlations of demographic characteristics with low health literacy risk in residents of Anhui province.A total of 5120 residents of Anhui province were interviewed in this cross-sectional survey, and 4816 (94.1%) gave valid responses. Sociodemographic characteristics were collected. Health literacy and its 3 subscales, including basic knowledge and concepts, lifestyle, and health-related skill, were assessed. Low health literacy was defined as <80.0% of the total score or score of each subscale.Mean total health literacy score was 62.7±17.2 (maximum 100 points), and was 31.5 ± 9.0 (maximum 47 points), 17.0 ± 4.8 (maximum 28 points), and 14.2 ± 4.1 (maximum 25 points) in terms of basic knowledge and concepts score, lifestyle score, and health-related skill score, respectively. The prevalence of low health literacy was 81.4%, and was 71.3% in terms of basic knowledge and concepts subscale, 87.9% with regard to lifestyle subscale, and 86.3% in view of health-related skill subscale. In addition, older age (P = .001), male (P < .001), decreased education level (P < .001), lower annual household income (P < .001), and location at rural area (P < .001) associated with increased risk of low health literacy. Moreover, multivariate logistic regression revealed that male, lower education level, and location at rural area were independent risk factors of low health literacy (all P < .05).The prevalence of low health literacy is high in residents of Anhui province, and male, lower education level, as well as location at rural area are independent risk factors of low health literacy.
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http://dx.doi.org/10.1097/MD.0000000000020547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7447391PMC
August 2020

Nutritional assessment and risk factors associated to malnutrition in patients with esophageal cancer.

Curr Probl Cancer 2021 Feb 14;45(1):100638. Epub 2020 Aug 14.

Department of Gastrointestinal Surgery/Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, The 9th Clinical College, PKU. No. 10 Tieyi Road, Haidian Dist, Beijing 100038, China. Electronic address:

Introduction: Esophageal cancer is the fourth most common cause of cancer death in China. Patients with esophageal cancer are more likely to suffer from malnutrition. The purpose of this study is to assess nutritional status of patients with esophageal cancer from multiple perspectives and analyze the risk factors.

Methods: A total of 1482 esophageal cancer patients were enrolled in the study. We investigated the Scored Patient Generated Subjective Global Assessment (PG-SGA) scores, NRS-2002 scores, Karnofsky performance status scores, anthropometric, and laboratory indicators of patients. Unconditional logistic regression analysis was applied to identify the risk factors of nutritional status.

Results: PG-SGA (≥4) and NRS-2002 (≥3) showed the incidence of malnutrition were 76% and 50%, respectively. In the patients with PG-SGA score ≥4, the proportion of patients who did not receive any nutritional support was 60%. The incidence of malnutrition in females was significantly higher than that in males. Besides, abnormality rates of Red blood cell (P < 0.001), MAC (P = 0.037), and MAMC (P < 0.001) in males was significantly higher than that in females, while abnormality rates of TSF (P < 0.001) was lower than that in females. After adjusted with the other potential risk factors listed, unconditional logistic regression analysis indicated smoking (odds ratio: 2.868, 95% confidence interval: 1.660-4.954), drinking (OR: 1.726, 95% CI: 1.099-2.712), family history (OR: 1.840, 95% CI: 1.132-2.992), radiotherapy or chemotherapy (OR: 1.594, 95% CI: 1.065-2.387), and pathological stage (OR: 2.263, 95% CI: 1.084-4.726) might be the risk factors of nutritional status, while nutritional support can reduce the risk of malnutrition.

Conclusion: Effective nutritional risk assessment methods and nutritional intervention measures can be adopted according to the research data to improve quality of life of esophageal cancer patients.
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http://dx.doi.org/10.1016/j.currproblcancer.2020.100638DOI Listing
February 2021

The patient-generated subjective global assessment is a promising screening tool for cancer cachexia.

BMJ Support Palliat Care 2020 Aug 21. Epub 2020 Aug 21.

Department of Gastrointestinal Surgery/Clinical Nutrition, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, China

Background: Cancer cachexia is a complex metabolic syndrome characterised by a loss of muscle with or without loss of fat mass, and is associated with high morbidity and mortality. Despite its clinical importance, there is a lack of simple tools to screen patients for cancer cachexia. The aim of this study was to evaluate and validate the patient-generated subjective global assessment (PG-SGA) as a screening tool for cancer cachexia.

Methods: This is a secondary analysis of a multicentre, cross-sectional, observational study. Cancer cachexia was diagnosed when there was weight loss ≥5% during the past 12 months and at least three of the five following conditions were present: decreased muscle strength, fatigue, anorexia, low Fat-Free Mass Index (FFMI) and abnormal laboratory findings. A quadratic discriminant analysis was conducted for the ability of PG-SGA to predict cachexia.

Results: A total of 4231 patients with cancer were included in this analysis, and 351 patients (8.3%) were diagnosed as having cachexia. The highest incidence of cachexia was found among patients with pancreatic cancer (32.5%), oesophageal cancer (21.5%) and gastric cancer (17.9%). Compared with patients without cachexia, patients with cachexia had a lower body mass index, FFMI, hand grip strength, total protein, prealbumin, albumin, haemoglobin and Karnofsky performance status (p<0.05), while they had a higher C reactive protein level and PG-SGA Score (4.71±3.71 vs 10.87±4.84, p<0.05). The best cut-off value for PG-SGA was 6.5, with 79.8% of sensitivity and 72.3% specificity for cachexia, and the area under the receiver operating characteristic curve was 0.846 (95% CI 0.826 to 0.866, p<0.001).

Conclusions: PG-SGA is a highly specific tool that can be used to screen patients for cancer cachexia.
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http://dx.doi.org/10.1136/bmjspcare-2020-002296DOI Listing
August 2020

Nutritional status and survival of 8247 cancer patients with or without diabetes mellitus-results from a prospective cohort study.

Cancer Med 2020 Oct 19;9(20):7428-7439. Epub 2020 Aug 19.

Department of Gastrointestinal Surgery/Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, The 9th Clinical College, Beijing, China.

Background: The number of cancer patients with diabetes mellitus (DM) is steadily rising. Little is known about the nutritional status of this population. This study characterized the nutritional status and survival of cancer patients with diabetes compared with those without diabetes.

Methods: A total of 8247 cancer patients were prospectively enrolled from 72 hospitals in China and followed until August 2019. A global estimation of the nutritional status was performed for each participant using standardized tools. The outcomes were cancer-specific survival (CSS) and overall survival (OS).

Results: The incidence of diabetes was 7.6% in the whole population. In comparison with the non-DM group, the DM group had greater body weight, but a similar fat-free mass, a lower handgrip strength and a decreased Karnofsky performance score. A higher proportion of patients with diabetes were overweight/obese as indicated by BMI. The percentage of patients who were at risk of malnutrition (evaluated by PG-SGA) was higher in the DM group (score ≥ 4, 56.7% vs 52.9%). Patients with DM showed a worse CSS (4-year CSS, 62% vs 73%) and OS (4-year OS 39% vs 52%). Diabetes was associated with an increased risk of both cancer-specific (hazard ratio (HR) = 1.282, 95% confidence interval (CI) 1.070-1.536) and overall (HR = 1.206, 95% CI 1.040-1.399) mortality.

Conclusions: Cancer patients with diabetes had a larger body mass but lower muscle strength, poorer performance status and higher incidence of malnourishment. Diabetes was associated with compromised survival. Tailored nutritional intervention is necessary for this subpopulation of patients.
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http://dx.doi.org/10.1002/cam4.3397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571830PMC
October 2020

Heterogeneous origins and functions of mouse skeletal muscle-resident macrophages.

Proc Natl Acad Sci U S A 2020 08 13;117(34):20729-20740. Epub 2020 Aug 13.

Department of Neurology, Boston University School of Medicine, Boston, MA 02118;

Tissue-resident macrophages can originate from embryonic or adult hematopoiesis. They play important roles in a wide range of biological processes including tissue remodeling during organogenesis, organ homeostasis, repair following injury, and immune response to pathogens. Although the origins and tissue-specific functions of resident macrophages have been extensively studied in many other tissues, they are not well characterized in skeletal muscle. In the present study, we have characterized the ontogeny of skeletal muscle-resident macrophages by lineage tracing and bone marrow transplant experiments. We demonstrate that skeletal muscle-resident macrophages originate from both embryonic hematopoietic progenitors located within the yolk sac and fetal liver as well as definitive hematopoietic stem cells located within the bone marrow of adult mice. Single-cell-based transcriptome analyses revealed that skeletal muscle-resident macrophages are distinctive from resident macrophages in other tissues as they express a distinct complement of transcription factors and are composed of functionally diverse subsets correlating to their origins. Functionally, skeletal muscle-resident macrophages appear to maintain tissue homeostasis and promote muscle growth and regeneration.
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http://dx.doi.org/10.1073/pnas.1915950117DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7456122PMC
August 2020

A Review of Advances in Hematopoietic Stem Cell Mobilization and the Potential Role of Notch2 Blockade.

Cell Transplant 2020 Jan-Dec;29:963689720947146

Department of Pathology, Case Western Reserve University, Cleveland, OH, USA.

Hematopoietic stem cell (HSC) transplantation can be a potential cure for hematological malignancies and some nonhematologic diseases. Hematopoietic stem and progenitor cells (HSPCs) collected from peripheral blood after mobilization are the primary source to provide HSC transplantation. In most of the cases, mobilization by the cytokine granulocyte colony-stimulating factor with chemotherapy, and in some settings, with the CXC chemokine receptor type 4 antagonist plerixafor, can achieve high yield of hematopoietic progenitor cells (HPCs). However, adequate mobilization is not always successful in a significant portion of donors. Research is going on to find new agents or strategies to increase HSC mobilization. Here, we briefly review the history of HSC transplantation, current mobilization regimens, some of the novel agents that are under investigation for clinical practice, and our recent findings from animal studies regarding Notch and ligand interaction as potential targets for HSPC mobilization.
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http://dx.doi.org/10.1177/0963689720947146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7563033PMC
August 2020

Metagenomic insights into differences in environmental resistome profiles between integrated and monoculture aquaculture farms in China.

Environ Int 2020 11 30;144:106005. Epub 2020 Jul 30.

Beijing Key Laboratory of Detection Technology for Animal-Derived Food Safety, College of Veterinary Medicine, China Agricultural University, Beijing, China. Electronic address:

Cumulative research on resistomes and microbiomes from aquatic environments has revealed that both integrated freshwater and monoculture freshwater aquaculture systems can cause the development and dissemination of antibiotic resistance genes (ARGs) and associated mobile genetic elements (MGEs). However, few studies have examined differences in resistomes between the different aquaculture modes, and those that do have focused on antibiotic residues or individual resistance genes. In the current study, we collected 44 environmental samples from two monoculture freshwater aquaculture farms and four integrated farms (two duck and fish farms, two laying duck and fish farms) in Guangdong, China, in 2018. After measuring the concentrations of antibiotic residues in the samples, we characterized MGEs and ARGs and examined their association with potential bacterial hosts in the microbial communities using high-throughput sequencing-based metagenomic and network analyses. We then compared the resistome profiles of the different aquaculture models. We found that the number and total relative abundance of ARG and MGE subtypes in the integrated (fish and duck/laying duck) farm samples were significantly higher than those in samples from monoculture freshwater aquaculture farms. Specifically, both the mobile colistin resistance genes mcr variants and tigecycline resistance gene tet(X) variants in integrated farms exhibited higher total relative abundance than that in monoculture farms. Moreover, the interrelationships among ARGs and microbial taxa, ARGs and MGEs, and MGEs and microbial taxa in the integrated farm samples were also more complex than those observed in monoculture freshwater aquaculture farm samples. Meanwhile, the species of Acinetobacter and Escherichia were identified to be the possible host of tet(X) and ESBL gene bla in aquaculture, respectively. To the best of our knowledge, this is the first metagenomic study to analyze differences in resistome profiles between integrated and monoculture ponds. Overall, integrated aquaculture systems exhibited a higher prevalence of resistance genes compared with monoculture freshwater aquaculture farms. Therefore, additional antimicrobial resistance surveillance should be focused on this type of freshwater aquaculture system.
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http://dx.doi.org/10.1016/j.envint.2020.106005DOI Listing
November 2020

Multi-class analysis of veterinary drugs in eggs using dispersive-solid phase extraction and ultra-high performance liquid chromatography-tandem mass spectrometry.

Food Chem 2021 Jan 18;334:127598. Epub 2020 Jul 18.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address:

A multi-residue method has been developed for the identification and quantification of 78 compounds from seven different classes of veterinary drugs in eggs. This method was based on dispersive solid phase extraction where mixed-mode cation exchange sorbent was used to combine the isolation of compounds and sample purification. The analysis was performed using ultra-high performance liquid chromatography-tandem mass spectrometry, and the chromatographic run time of one injection was 9.5 min. The mean recovery ranged from 70.5% to 119.2% and inter-day relative standard deviation was less than 17.0%. The limit of quantification ranged between 0.1 and 1 μg/kg, which was sufficient to support surveillance monitoring. Lastly, the method was successfully used to detect residues of veterinary drug in real samples. The dietary exposure risk was subsequently assessed using the results of the survey, indicating that the evaluated daily intake and percentage of acceptable daily intake were at toxicologically acceptable levels.
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http://dx.doi.org/10.1016/j.foodchem.2020.127598DOI Listing
January 2021

Peritumoral/vascular expression of PSMA as a diagnostic marker in hepatic lesions.

Diagn Pathol 2020 Jul 23;15(1):92. Epub 2020 Jul 23.

Department of Pathology, University Hospital Cleveland Medical Center, Case Western Reserve University, 10900 Euclid Ave, Cleveland, Ohio, 44106, USA.

Background: The differential diagnosis between primary cholangiocarcinoma and metastatic pancreatobiliary adenocarcinoma is histologically challenging due to lack of distinct morphological features and reliable molecular markers. Prostate-specific membrane antigen (PSMA) is expressed in prostate epithelium and upregulated on the surface of prostatic adenocarcinoma cells. Studies have shown PSMA enzymatic activity is involved in malignancy-driven neoangiogenesis in the endothelium of tumor-associated neovasculature in breast, lung, thyroid, hepatocellular carcinoma (HCC) and urothelial cancer. Recently, PSMA-targeted imaging technology (PSMA PET-CT) detected the presence of PSMA in primary cholangiocarcinoma. However histological correlation with PSMA expression other mass lesions in the liver has not yet been studied.

Methods: 72 cases of liver mass resection were collected at a tertiary hospital from 2011 to 2019. Immunohistochemical stains for PSMA and CD34 were performed. The expression of PSMA in tumor cells and associated neovascular endothelium were analyzed separately and the locations of vascular structures were confirmed by CD34 expression.

Results: Among 72 cases, 28 cases (22/72, 38.9%) showed PSMA peritumoral/vascular expression only, 3 cases (3/72, 4.2%) showed tumor cell expression only, and 2 cases (2/72, 2.8%) showed both tumor cell and peritumoral/vascular expression. The remainder (39/72, 54.2%) showed no expression. Particularly, most of primary cholangiocarcinoma showed PSMA vascular expression (13/15, 86.7%), while none of the 18 cases of metastatic pancreatobiliary adenocarcinoma were positive for PSMA (0/18, 0%) (p < 0.01). Outside of pancreatobiliary adenocarcinoma, none of the metastatic tumors, including colon and lung cancers, expressed PSMA. In 8 cases of metastatic prostate carcinoma, 3 showed PSMA expressions in tumor cells only (3/8, 37.5%) and 2 expressed PMSA in both tumor cells and neovasculature (2/8, 25.0%). Out of 22 HCC cases, 15 (15/22, 68.2%) were positive for PSMA in tumor vasculature. None of the 5 hepatic adenoma expressed PSMA (0/5, 0%).

Conclusion: Significantly enhanced tumor-associated neovascular PSMA expression was identified in primary cholangiocarcinoma, compared to metastatic pancreatobiliary adenocarcinoma. Our findings potentially provide a sensitive marker in differential diagnosis between otherwise morphologically indistinguishable cases.
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http://dx.doi.org/10.1186/s13000-020-00982-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7376868PMC
July 2020

A novel pentacyclic triterpene from the canes of (Rubiaceae).

Nat Prod Res 2020 Jul 21:1-6. Epub 2020 Jul 21.

CAS Key Laboratory of Tropical Plant Resources and Sustainable Use, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Kunming, P. R. China.

One novel pentacyclic triterpene, 24-dimethoxymethyl-3,6,19- trihydroxy -12-en-28-oic acid (), along with six known compounds -, were isolated from the canes of Roxb. Their structures were determined according to spectroscopic and spectrometric analysis. The anti-inflammatory activities of the isolated compounds (-) were scanned against NO production in LPS-activated RAW 264.7 macrophages by MTS assay, however no activities were observed.
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http://dx.doi.org/10.1080/14786419.2020.1795856DOI Listing
July 2020

Influence of Saline Buffers over the Stability of High-Annealed Gold Nanoparticles Formed on Coverslips for Biological and Chemosensing Applications.

Bioengineering (Basel) 2020 Jul 3;7(3). Epub 2020 Jul 3.

Laboratory Light, nanomaterials and nanotechnologies - L2n, CNRS ERL 7004, University of Technology of Troyes, 12 rue Marie Curie, 10004 Troyes, France.

Herein, coverslips were used as solid supports for the synthesis of gold nanoparticles (AuNPs) in three steps: (i) detergent cleaning, (ii) evaporation of 4 nm gold film and (iii) exposure at high annealing temperature (550 °C) for 3 h. Such active gold nanostructured supports were investigated for their stability performances in aqueous saline buffers for new assessments of chemical sensing. Two model buffers, namely saline-sodium phosphate-EDTA buffer (SSPE) and phosphate buffer saline (PBS), that are often used in the construction of (bio)sensors, are selected for the optical and microscopic investigations of their influence over the stability of annealed AuNPs on coverslips when using a dropping procedure under dry and wet media working conditions. A study over five weeks monitoring the evolution of the localized surface plasmon resonance (LSPR) chemosensing of 1,2-bis-(4-pyridyl)-ethene (BPE) is discussed. It is concluded that the optimal sensing configuration is based on annealed AuNPs exposed to saline buffers under wet media conditions (overnight at 4 °C) and functionalized with BPE concentrations (10-10 M) with the highest LSPR spectra after two weeks.
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http://dx.doi.org/10.3390/bioengineering7030068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7552610PMC
July 2020

Association of florfenicol residues with the abundance of oxazolidinone resistance genes in livestock manures.

J Hazard Mater 2020 11 28;399:123059. Epub 2020 May 28.

Beijing Advanced Innovation Center for Food Nutrition and Human Health, College of Veterinary Medicine, China Agricultural University, Beijing 100193, China. Electronic address:

Livestock and poultry manures are major reservoirs of antibiotic-resistant bacteria and antibiotic resistance genes (ARGs). Linezolid is a clinical medicine for humans and has never been approved for use in livestock. Interestingly, three linezolid resistance genes (cfr, optrA, and poxtA) have been detected in bacteria of animal origin, arousing public concern. This study investigated the abundance of three ARGs, cfr, optrA, and poxtA, in manures from 157 large-scale farms in China using real-time quantitative polymerase chain reaction. The residual concentrations of linezolid, florfenicol, tiamulin, and valnemulin were determined using ultra-high performance liquid chromatography-tandem mass spectrometry. A total of 140 livestock farms were tested positive for ARGs, and the positive detection rate was 89.17 %. OptrA was the most commonly detected ARG. The diversity and abundance of ARGs were significantly higher in poultry and swine manure than in bovine manure. Redundancy analysis presented a strong association between florfenicol and all the three ARGs targeted in the study, and tiamulin showed a significant correlation with optrA. Our results indicated that the residual concentration of florfenicol had a major effect on the distribution of the three ARGs in livestock manures, and extensive use of florfenicol may lead to the production of linezolid resistance genes.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123059DOI Listing
November 2020