Publications by authors named "Rong Zhu"

373 Publications

Differential expression and role of miR-200 family in multiple tumors.

Anal Biochem 2021 May 5:114243. Epub 2021 May 5.

Department of Gastroenterology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, PR China. Electronic address:

microRNA (miRNA) can maintain the homeostasis of the human by participating in the regulation of cell proliferation, apoptosis, differentiation, and metabolism. During the entire stage of tumorigenesis, miRNA can maintain the heterogeneity of cancer stem cells by regulating the formation and metastasis of the tumor, which leads to chemotherapy resistance. miR-200 family consists of five members, which can regulate the proliferation, invasion, and migration of cancer cells by inhibiting the transcription of downstream genes (including zinc finger E-box binding homeobox 1 and 2, E-cadherin, N-cadherin, transforming growth factor-β, and cancer stem cell related-proteins). Meanwhile, Long non-coding RNA can bind to miR-200s to regulate the proliferation and apoptosis of cancer cells. Besides, the expression of the miR-200 family can affect the mechanism of chemotherapy resistance.
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http://dx.doi.org/10.1016/j.ab.2021.114243DOI Listing
May 2021

Highly chemoselective synthesis of hindered amides via cobalt-catalyzed intermolecular oxidative hydroamidation.

Nat Commun 2021 05 5;12(1):2552. Epub 2021 May 5.

Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing, China.

α-Tertiary amides are of great importance for medicinal chemistry. However, they are often challenging to access through conventional methods due to reactivity and chemoselectivity issues. Here, we report a single-step approach towards such amides via cobalt-catalyzed intermolecular oxidative hydroamidation of unactivated alkenes, using nitriles of either solvent- or reagent-quantities. This protocol is selective for terminal alkenes over groups that rapidly react under known carbocation amidation conditions such as tertiary alcohols, electron-rich alkenes, ketals, weak C-H bonds, and carboxylic acids. Straightforward access to a diverse array of hindered amides is demonstrated, including a rapid synthesis of an aminoadamantane-derived pharmaceutical intermediate.
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http://dx.doi.org/10.1038/s41467-021-22373-zDOI Listing
May 2021

Measurement of Electric Double Layer Capacitance Using Dielectrophoresis-Based Particle Manipulation.

Anal Chem 2021 Apr 2;93(14):5882-5889. Epub 2021 Apr 2.

State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China.

An electric double layer (EDL) generally exists at the interface between a conductive electrode and its adjacent liquid electrolyte. Accurate measurement of the capacitance of EDL is requisite but a great challenge due to the complexity of its variation mechanism correlated with the magnitude and frequency of applied signals and the difficulty in measuring the inner layer potentials across the EDL. Herein, a novel dielectrophoresis (DEP)-based approach is proposed to measure the capacitance of an EDL at a microelectrode/electrolyte interface. The measurement is achieved by employing DEP manipulation to micro polystyrene (PS) spheres suspended in a liquid electrolyte and determining the capacitance of EDL on the microelectrodes from the moving velocities of spheres. This method allows measurement of the capacitances of EDL under alternating current (AC) signals with different magnitudes and frequencies, so that the capacitance change with the magnitude and frequency of the applied signal can be characterized. The method avoids the impedance interference from the liquid electrolyte, external measuring systems, and other crosstalks, enabling an accurate measurement of double layer capacitance. In addition, the inner layer potentials across EDL under different magnitudes and frequencies of applied signals are comprehensively investigated, which facilitates an understanding of the ion behavior at the interfacial boundary that governs external observations of electrochemical reactions. The accurate measurement of the capacitance of EDL is of significance to explore the mechanism of interfacial functioning of electrochemical and bioelectrical devices and systems.
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http://dx.doi.org/10.1021/acs.analchem.1c00226DOI Listing
April 2021

IPCARF: improving lncRNA-disease association prediction using incremental principal component analysis feature selection and a random forest classifier.

BMC Bioinformatics 2021 Apr 1;22(1):175. Epub 2021 Apr 1.

School of Computer Science, Qufu Normal University, Rizhao, China.

Background: Identifying lncRNA-disease associations not only helps to better comprehend the underlying mechanisms of various human diseases at the lncRNA level but also speeds up the identification of potential biomarkers for disease diagnoses, treatments, prognoses, and drug response predictions. However, as the amount of archived biological data continues to grow, it has become increasingly difficult to detect potential human lncRNA-disease associations from these enormous biological datasets using traditional biological experimental methods. Consequently, developing new and effective computational methods to predict potential human lncRNA diseases is essential.

Results: Using a combination of incremental principal component analysis (IPCA) and random forest (RF) algorithms and by integrating multiple similarity matrices, we propose a new algorithm (IPCARF) based on integrated machine learning technology for predicting lncRNA-disease associations. First, we used two different models to compute a semantic similarity matrix of diseases from a directed acyclic graph of diseases. Second, a characteristic vector for each lncRNA-disease pair is obtained by integrating disease similarity, lncRNA similarity, and Gaussian nuclear similarity. Then, the best feature subspace is obtained by applying IPCA to decrease the dimension of the original feature set. Finally, we train an RF model to predict potential lncRNA-disease associations. The experimental results show that the IPCARF algorithm effectively improves the AUC metric when predicting potential lncRNA-disease associations. Before the parameter optimization procedure, the AUC value predicted by the IPCARF algorithm under 10-fold cross-validation reached 0.8529; after selecting the optimal parameters using the grid search algorithm, the predicted AUC of the IPCARF algorithm reached 0.8611.

Conclusions: We compared IPCARF with the existing LRLSLDA, LRLSLDA-LNCSIM, TPGLDA, NPCMF, and ncPred prediction methods, which have shown excellent performance in predicting lncRNA-disease associations. The compared results of 10-fold cross-validation procedures show that the predictions of the IPCARF method are better than those of the other compared methods.
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http://dx.doi.org/10.1186/s12859-021-04104-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8017839PMC
April 2021

Asymmetric Core-Shell Gold Nanoparticles and Controllable Assemblies for SERS Ratiometric Detection of MicroRNA.

Angew Chem Int Ed Engl 2021 Mar 26. Epub 2021 Mar 26.

MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou, 350108, P. R. China.

Janus nanogap gold nanoparticles (JAuNNPs) with varying proportions of Au shell coverage of (ca. 100/75/50/25 %) are presented. The internal nanogap between the partial Au shell and core caused asymmetric optical behavior; tunability depends on the degree of Au shell coverage and structural asymmetry. The shell-to-shell or core-to-core JAuNNDs(50 %) were self-assembled from amphiphilic JAuNNPs(50 %) by tuning the hydrophilic and hydrophobic polymer brushes on the Au core or shell. The positions of electromagnetic field enhancement of JAuNNDs varied with geometrical configurations because of hybridized plasmonic coupling effects. Furthermore, DNA linkers were utilized to form JAuNND (50 %). By combining with Raman molecules, ratiometric SERS signals could be generated, enabling JAuNND (50 %) to image the distribution of miR-21 in living cells and tumors. Asymmetric JAuNNPs allowed facile conjugation of various linkage molecules to fabricate dimeric nanostructures.
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http://dx.doi.org/10.1002/anie.202102893DOI Listing
March 2021

Model averaging estimation for high-dimensional covariance matrices with a network structure.

Econom J 2021 Jan 29;24(1):177-197. Epub 2020 Sep 29.

School of Mathematical Sciences, Capital Normal University, Beijing 100048, China.

In this paper, we develop a model averaging method to estimate a high-dimensional covariance matrix, where the candidate models are constructed by different orders of polynomial functions. We propose a Mallows-type model averaging criterion and select the weights by minimizing this criterion, which is an unbiased estimator of the expected in-sample squared error plus a constant. Then, we prove the asymptotic optimality of the resulting model average covariance estimators. Finally, we conduct numerical simulations and a case study on Chinese airport network structure data to demonstrate the usefulness of the proposed approaches.
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http://dx.doi.org/10.1093/ectj/utaa030DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7946866PMC
January 2021

Unintended changes in ocular biometric parameters during a 6-month follow-up period after FS-LASIK and SMILE.

Eye Vis (Lond) 2021 Mar 19;8(1). Epub 2021 Mar 19.

School of Engineering, University of Liverpool, Liverpool, L69 3GH, UK.

Background: Corneal refractive surgery has become reliable for correcting refractive errors, but it can induce unintended ocular changes that alter refractive outcomes. This study is to evaluate the unintended changes in ocular biometric parameters over a 6-month follow-up period after femtosecond laser-assisted laser in situ keratomileusis (FS-LASIK) and small incision lenticule extraction (SMILE).

Methods: 156 consecutive myopic patients scheduled for FS-LASIK and SMILE were included in this study. Central corneal thickness (CCT), mean curvature of the corneal posterior surface (K), internal anterior chamber depth (IACD) and the length from corneal endothelium to retina (ER) were evaluated before and after surgery over a 6-month period.

Results: Both the FS-LASIK and SMILE groups (closely matched at the pre-surgery stage) experienced flatter K, shallower IACD and decreased ER 1 week post-surgery (P < 0.01), and these changes were larger in FS-LASIK than in SMILE group. During the 1 week to 6 months follow up period, K, IACD and ER remained stable unlike CCT which increased significantly (P < 0.05), more in the FS-LASIK group.

Conclusions: During the follow up, the posterior corneal surface became flatter and shifted posteriorly, the anterior chamber depth and the length from the corneal endothelium to retina decreased significantly compared with the pre-surgery stage. These unintended changes in ocular biometric parameters were greater in patients undergoing FS-LASIK than SMILE. The changes present clear challenges for IOL power calculations and should be considered to avoid affecting the outcome of cataract surgery.
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http://dx.doi.org/10.1186/s40662-021-00232-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7977186PMC
March 2021

Asymmetric cortical development and prognosis in fetuses with isolated mild fetal ventriculomegaly: an observational prospective study.

BMC Pregnancy Childbirth 2021 Mar 10;21(1):199. Epub 2021 Mar 10.

Department of Pediatrics, Peking University First Hospital, No. 1 Xi-An-Men Street, Xi-Cheng District, Beijing, 100034, China.

Background: Assessments of cortical development and identifying factors that may result in a poor prognosis for fetuses with isolated mild ventriculomegaly (IMVM) is a hot research topic. We aimed to perform a constant, detailed assessment of cortical development in IMVM fetuses using ultrasound and determine whether asymmetric cortical development occurred. Moreover, we aimed to estimate the prognosis of IMVM fetuses and compare the difference in the prognosis of IMVM fetuses presenting symmetric and asymmetric cortical maturation.

Methods: IMVM was diagnosed by regular ultrasound, neurosonography and fetal MRI. Genetic and TORCH examinations were conducted to exclude common genetic abnormalities and TORCH infection of fetuses. Ultrasound examinations were conducted at an interval of 2-3 weeks to record sulcus development in IMVM fetuses using a scoring system. The neonatal behavioral neurological assessment (NBNA), the Ages and Stages Questionnaire, Third Edition (ASQ-3) and the Bayley Scales of Infant Development, First Edition (BSID-I) were performed after birth.

Results: Forty fetuses with IMVM were included: twenty showed asymmetric cortical maturation and twenty showed symmetric cortical maturation. For IMVM fetuses presenting asymmetric cortical maturation, the mean gestational age (GA) at the first diagnosis of relatively delayed development was 24.23 weeks for the parieto-occipital sulcus, 24.71 weeks for the calcarine sulcus, and 26.43 weeks for the cingulate sulcus. All the sulci with delayed development underwent 'catch-up growth' and developed to the same grade as the sulci of the other hemisphere. The mean GA at which the two sides developed to the same grade was 29.40 weeks for the parieto-occipital sulcus, 29.30 weeks for the calcarine sulcus and 31.27 weeks for the cingulate sulcus. The NBNA, ASQ-3 and BSID-I scores of all patients were in the normal range.

Conclusions: IMVM fetuses may show mild asymmetric cortical maturation in the second trimester, but the relatively delayed sulci undergo 'catch-up growth'. The neurodevelopment of IMVM fetuses presenting asymmetric cortical maturation and 'catch-up growth' is not statistically significantly different from IMVM fetuses presenting symmetric cortical maturation.
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http://dx.doi.org/10.1186/s12884-021-03692-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7945606PMC
March 2021

Shenfu injection combined with furosemide in the treatment of chronic heart failure in patients with coronary heart disease: A protocol of randomized controlled trial.

Medicine (Baltimore) 2021 Jan;100(3):e24113

Department of Emergency Medicine, The Second Affiliated Hospital of Nanjing Medical University, Nanjing 210011, Jiangsu Province, China.

Background: Coronary heart disease (CHD) is an important cause of chronic heart failure, and chronic heart failure is also a serious complication in the end stage of coronary heart disease. At present, there is no specific treatment plan. Shenfu injection has advantages in the treatment of heart failure in patients with coronary heart disease, but there is a lack of standard clinical study to verify this. Therefore, the purpose of this randomized controlled trial is to evaluate the efficacy and safety of Shenfu injection combined with furosemide in the treatment of chronic heart failure in patients with coronary heart disease.

Methods: This is a prospective randomized controlled trial to study the efficacy and safety of Shenfu injection combined with furosemide in the treatment of coronary heart disease and chronic heart failure. This study will be approved by the clinical research ethics committee of our hospital. The patients will be randomly divided into two groups according to 1:1:(a) Shenfu injection combined with furosemide group and (b) simple furosemide group. Standard treatment for 7 days followed up for 30 days at the same time, pay attention to its efficacy and safety indicators. The total effective rate of cardiac function improvement, left ventricular ejection fraction (LVEF), N-terminal pro-brain natriuretic peptide (NT-pro BNP), 6-minute walk test (6-MWTD), and adverse reactions will be observed. Data will be analyzed using the statistical software package SPSS version 25.0 (Chicago, IL).

Discussion: This study will evaluate the efficacy and safety of Shenfu injection combined with furosemide in the treatment of coronary heart disease with chronic heart failure. The results of this experiment will provide a clinical basis for Shenfu injection combined with furosemide in the treatment of coronary heart disease and chronic heart failure.

Osf Registration Number: doi: 10.17605/OSF.IO/27FPM.
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http://dx.doi.org/10.1097/MD.0000000000024113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7837985PMC
January 2021

Quantitative Assessment of Copper(II) in Wilson's Disease Based on Photoacoustic Imaging and Ratiometric Surface-Enhanced Raman Scattering.

ACS Nano 2021 02 28;15(2):3402-3414. Epub 2021 Jan 28.

MOE Key Laboratory for Analytical Science of Food Safety and Biology, College of Chemistry, Fuzhou University, Fuzhou 350108, China.

Cu is closely related to the occurrence and development of Wilson's disease (WD), and quantitative detection of various copper indicators (especially liver Cu and urinary Cu) is the key step for the early diagnosis of WD in the clinic. However, the clinic Cu detection approach was mainly based on testing the liver tissue through combined invasive liver biopsy and the ICP-MS method, which is painful for the patient and limited in determining WD status in real-time. Herein, we rationally designed a type of Cu-activated nanoprobe based on nanogapped gold nanoparticles (AuNNP) and poly(-isopropylacrylamide) (PNIPAM) to simultaneously quantify the liver Cu content and urinary Cu in WD by photoacoustic (PA) imaging and ratiometric surface-enhanced Raman scattering (SERS), respectively. In the nanoprobe, one Raman molecule of 2-naphthylthiol (NAT) was placed in the nanogap of AuNNP. PNIPAM and the other Raman molecule mercaptobenzonitrile (MBN) were coated on the AuNNP surface, named AuNNP-NAT@MBN/PNIPAM. Cu can efficiently coordinate with the chelator PNIPAM and lead to aggregation of the nanoprobe, resulting in the absorption red-shift and increased PA performance of the nanoprobe in the NIR-II window. Meanwhile, the SERS signal at 2223 cm of MBN is amplified, while the SERS signal at 1378 cm of NAT remains stable, generating a ratiometric SERS / signal. Both NIR-II PA and SERS / signals of the nanoprobe show a linear relationship with the concentration of Cu. The nanoprobe was successfully applied for quantitative detection of liver Cu of WD mice through NIR-II PA imaging and accurate quantification of urinary Cu of WD patients by ratiometric SERS. We anticipate that the activatable nanoprobe might be applied for assisting an early, precise diagnosis of WD in the clinic in the future.
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http://dx.doi.org/10.1021/acsnano.0c10407DOI Listing
February 2021

The dynamics and release characteristics of microcystins in the plateau Lake Erhai, Southwest China.

Environ Sci Pollut Res Int 2021 Jan 15. Epub 2021 Jan 15.

Donghu Experimental Station of Lake Ecosystems, State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, 430072, People's Republic of China.

Microcystins (MCs) have seriously polluted drinking water supplies and have caused great harm to aquatic organisms and humans. Understanding the dynamics of MC concentrations and its influencing factors is necessary for drinking water safety. Many previous studies on MC pollution focused on intracellular MCs rather than on extracellular MCs, which are more difficult to remove by water treatment. So far, the release characteristics of MCs and the relationships between intracellular and extracellular MCs are still unclear. To explore these questions, a survey was conducted at 18 sites across Lake Erhai from May 2014 to April 2015 as in Lake Erhai the frequency and coverage area of cyanobacterial blooms have been increasing. Variation of extracellular MCs lagged behind that of intracellular MCs. The highest value of intracellular MCs was 1.07 μg L in October 2014 and the highest extracellular MC concentration was 0.035 μg L in November 2014. Intracellular MCs were positively influenced by MC-producing cyanobacterial biomass, water temperature (WT), pH, and conductivity (Cond). The extracellular MCs showed little correlation with cyanobacterial abundances and intracellular MC concentrations, but showed significant negative correlations with WT, pH, and Cond. These results indicated that high biomass and high intracellular MC concentrations did not quickly lead to large releases of MCs, and that when cyanobacterial cells died and blooms disappeared, MCs were intensively released into the water, posing the greatest threat to drinking water supply.
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http://dx.doi.org/10.1007/s11356-020-12312-8DOI Listing
January 2021

Skin-inspired quadruple tactile sensors integrated on a robot hand enable object recognition.

Sci Robot 2020 12;5(49)

State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China.

Robot hands with tactile perception can improve the safety of object manipulation and also improve the accuracy of object identification. Here, we report the integration of quadruple tactile sensors onto a robot hand to enable precise object recognition through grasping. Our quadruple tactile sensor consists of a skin-inspired multilayer microstructure. It works as thermoreceptor with the ability to perceive thermal conductivity of a material, measure contact pressure, as well as sense object temperature and environment temperature simultaneously and independently. By combining tactile sensing information and machine learning, our smart hand has the capability to precisely recognize different shapes, sizes, and materials in a diverse set of objects. We further apply our smart hand to the task of garbage sorting and demonstrate a classification accuracy of 94% in recognizing seven types of garbage.
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http://dx.doi.org/10.1126/scirobotics.abc8134DOI Listing
December 2020

Electrical stimulation at nanoscale topography boosts neural stem cell neurogenesis through the enhancement of autophagy signaling.

Biomaterials 2021 Jan 2;268:120585. Epub 2020 Dec 2.

Department of Ophthalmology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, PR China; State Key Laboratory of Brain and Cognitive Sciences, The University of Hong Kong, Hong Kong SAR, PR China. Electronic address:

Neural stem cells (NSCs) transplantation at the injury site of central nerve system (CNS) makes it possible for neuroregeneration. Long-term cell survival and low proliferation, differentiation, and migration rates of NSCs-graft have been the most challenging aspect on NSCs application. New multichannel electrical stimulation (ES) device was designed to enhance neural stem cells (NSCs) differentiation into mature neurons. Compared to controls, ES at nanoscale topography enhanced the expression of mature neuronal marker, growth of the neurites, concentration of BDNF and electrophysiological activity. RNA sequencing analysis validated that ES promoted NSC-derived neuronal differentiation through enhancing autophagy signaling. Emerging evidences showed that insufficient or excessive autophagy contributes to neurite degeneration. Excessive ES current were able to enhance neuronal autophagy, the neuronal cells showed poor viability, reduced neurite outgrowth and electrophysiological activity. Well-controlled autophagy not only protects against neurodegeneration, but also regulates neurogenesis. Current NSC treatment protocol efficiently enhanced NSC differentiation, maturation and survival through combination of proper ES condition followed by balance of autophagy level in the cell culture system. The successful rate of such protreated NSC at injured CNS site should be significantly improved after transplantation.
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http://dx.doi.org/10.1016/j.biomaterials.2020.120585DOI Listing
January 2021

Effects of Multiple-Hole Baffle Arrangements on Flow Fields in a Five-Strand Asymmetric Tundish.

Materials (Basel) 2020 Nov 13;13(22). Epub 2020 Nov 13.

Tangshan Xinbaotai Steel Co., Ltd., Tangshan 064000, China.

This paper reports on the re-engineering of standard five-strand tundish designs into a five-strand asymmetric tundish, which resulted in a non-uniform rate and bias for each strand. We sought to improve the casting conditions by optimizing the liquid steel flow-field in the tundish. Both a water modelling experiment and a numerical simulation were performed to analyze the flow-field according to various diversion hole diameters and injection angles. The results showed that the average residence time decreased as the diameter of the diversion holes increased. As the injection angle was increased, the average residence time initially decreased and then increased. The liquid steel from the ladle shroud rapidly extended to the #2 and #3 strands in the original tundish, which reduced the likelihood of inclusion collision and coalescence.
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http://dx.doi.org/10.3390/ma13225129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696384PMC
November 2020

A wearable motion capture device able to detect dynamic motion of human limbs.

Nat Commun 2020 11 5;11(1):5615. Epub 2020 Nov 5.

State Key Laboratory of Precision Measurement Technology and Instrument, Department of Precision Instrument, Tsinghua University, Beijing, 100084, China.

Limb motion capture is essential in human motion-recognition, motor-function assessment and dexterous human-robot interaction for assistive robots. Due to highly dynamic nature of limb activities, conventional inertial methods of limb motion capture suffer from serious drift and instability problems. Here, a motion capture method with integral-free velocity detection is proposed and a wearable device is developed by incorporating micro tri-axis flow sensors with micro tri-axis inertial sensors. The device allows accurate measurement of three-dimensional motion velocity, acceleration, and attitude angle of human limbs in daily activities, strenuous, and prolonged exercises. Additionally, we verify an intra-limb coordination relationship exists between thigh and shank in human walking and running, and establish a neural network model for it. Using the intra-limb coordination model, dynamic motion capture of human lower limbs including thigh and shank is tactfully implemented by a single shank-worn device, which simplifies the capture device and reduces cost. Experiments in strenuous activities and long-time running validate excellent performance and robustness of the wearable device in dynamic motion recognition and reconstruction of human limbs.
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http://dx.doi.org/10.1038/s41467-020-19424-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645594PMC
November 2020

Single molecule distribution of RhD binding epitopes on ultraflat erythrocyte ghosts.

Nanoscale 2020 Nov;12(43):22097-22106

Molecular Biosensing group, Institute of Biophysics, Johannes Kepler University Linz, Austria.

The Rh blood group system plays a key role in transfusion and organ transplant medicine. The complex transmembrane Rh polypeptides RhD and RhCE carry numerous antigens, including the extremely immunogenic D antigen. The Rh polypeptides form multimolecular Rh complexes with certain transmembrane and skeletal proteins, with so far only incompletely understood physiological functions. Determination of the energy landscape of individual Rh binding epitopes towards their specific interaction partners as well as their localization across the red blood cell (RBC) membrane requires single molecule approaches including large area high resolution recognition imaging. Atomic force microscopy based molecular recognition force spectroscopy in combination with single molecule recognition imaging fulfills these requirements. For unbiased single molecule results, nano-mechanical influences due to cell elasticity have to be eliminated. This is realized by generation of ultra flat erythrocyte ghosts on a solid support. We developed a protocol for the preparation of complete ultraflat erythrocyte ghosts and determined the molecular binding behaviour of different anti-D antibodies towards their binding epitopes on RhD positive and negative erythrocytes. Performing optimized topography and recognition imaging at 16 Mpixel resolution allowed localisation of individual RhD molecules at the single molecule level across an entire RBC. A map of Rh antigens across integer ultraflat RBC ghosts was generated with nanometer resolution. Here we show a homogeneous distribution on rim and dimple regions with comparable receptor densities. Furthermore, differences in the energy landscape between specific monoclonal antibodies were determined at the single molecule level.
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http://dx.doi.org/10.1039/d0nr04393aDOI Listing
November 2020

Long-term and label-free monitoring for osteogenic differentiation of mesenchymal stem cells using force sensor and impedance measurement.

J Mater Chem B 2020 11;8(43):9913-9920

State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing, 100084, China.

Stem cells have attracted increasing research interest in the field of regenerative medicine due to their unique abilities to differentiate into multiple cell lineages. Label-free, real-time, and long-term monitoring for stem cell differentiation is requisite in studying directional differentiation and development mechanisms for tissue engineering applications, but a great challenge because of the rigorous demands for sensitivity, stability and biocompatibility of devices. In this article, a label-free and real-time monitoring approach using a zinc oxide (ZnO) nanorod field effect transistor (FET) is proposed to detect cell traction forces (CTFs) exerted by cells on underlying substrates. The ZnO nanorod FET with the approach of difference-frequency lock-in detection achieves high sensitivity, good stability, and excellent biocompatibility, by which real-time and long-term (over 20 days) monitoring of cellular mechanical changes in osteogenic differentiation of mesenchymal stem cells (MSCs) is successfully achieved. We also employ electrical impedance monitoring using microelectrode array chips and microscopic observation to investigate cell migration and nodular aggregation behaviors of MSCs in osteogenic differentiation. Various biochemical assays including alkaline phosphatase (ALP), osteopontin expression and alizarin red staining are utilized to verify osteogenic differentiation of MSCs. We propose a combination of cell traction force measurement, impedance measurement and microscopic observation to provide multimodal profiling of cell morphology, and cellular biomechanical and electrophysiological phenotypes, which can track cellular dynamics in stem cell development and help to deeply understand the mechanism of osteogenic differentiation.
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http://dx.doi.org/10.1039/d0tb01968bDOI Listing
November 2020

Red elemental selenium (Se ) improves the immunoactivities of EPC cells, crucian carp and zebrafish against spring viraemia of carp virus.

J Fish Biol 2021 Jan 16;98(1):208-218. Epub 2020 Oct 16.

State Key Laboratory of Biocatalysis and Enzyme Engineering, The Faculty of Life Science, Hubei University, Wuhan, China.

Selenium, as an essential trace element, interferes through selenoproteins in many physiological processes of plants and mammals. Its antiviral activity has recently attracted much attention because selenium improves the antiviral capacity of animal cells against a few viruses relevant to human diseases. In this study, the red elemental selenium was purified from the fermentative culture of Herbaspirillum camelliae WT00C and then used to culture epithelioma papulosum cyprinid (EPC) cells or feed crucian carp and zebrafish. Finally, its antiviral effects were investigated at the cell level and living fishes after spring viraemia of carp virus infection. At the cell level, 5, 10 and 20 μg ml red elemental selenium significantly induced the expression of interferon (IFN) and ISG15 genes in EPC cells. The viral TCID (50% tissue culture infective dose) values in the EPC cells incubated with 5, 10 and 20 μg ml red elemental selenium were significantly less than those of the control. More expression of IFN and ISG15 genes and less TCID values indicate that red elemental selenium indeed improves the antiviral capability of EPC cells. In the crucian carp fed with the food containing 5 and 10 μg g red elemental selenium, IFN expressions showed 13- and 39-fold increases at the 16th day of post-injection, and its expression was dependent on selenium concentrations. Meanwhile, no fish death occurred in all the experimental groups. In the zebrafish fed with the red worm containing 5 μg g red elemental selenium, IFN and Mx expressions and survival rate were significantly higher than those of the control. The results of this study show that red elemental selenium indeed improves the antiviral activity of fish. The antiviral effects of selenium mainly come from its immune regulation through its incorporation into selenoproteins. The optimum level of selenium contributes to improving fish immunity, whereas excess selenium causes excessive immune and inflammatory responses.
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http://dx.doi.org/10.1111/jfb.14571DOI Listing
January 2021

L-Extreme Learning Machine: An Efficient Robust Classifier for Tumor Classification.

Comput Biol Chem 2020 Dec 1;89:107368. Epub 2020 Sep 1.

School of Information Science and Engineering, Qufu Normal University, Rizhao, China. Electronic address:

With the development of cancer research, various gene expression datasets containing cancer information show an explosive growth trend. In addition, due to the continuous maturity of single-cell RNA sequencing (scRNA-seq) technology, the protein information and pedigree information of a single cell are also continuously mined. It is a technical problem of how to classify these high-dimensional data correctly. In recent years, Extreme Learning Machine (ELM) has been widely used in the field of supervised learning and unsupervised learning. However, the traditional ELM does not consider the robustness of the method. To improve the robustness of ELM, in this paper, a novel ELM method based on L-norm named L-Extreme Learning Machine (L -ELM) has been proposed. The method introduces L-norm on loss function to improve the robustness, and minimizes the influence of noise and outliers. Firstly, we evaluate the new method on five UCI datasets. The experiment results prove that our method can achieve competitive results. Next, the novel method is applied to the problem of classification of cancer samples and single-cell RNA sequencing datasets. The experimental results on The Cancer Genome Atlas (TCGA) datasets and scRNA-seq datasets prove that ELM and its variants has great potential in the classification of cancer samples.
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http://dx.doi.org/10.1016/j.compbiolchem.2020.107368DOI Listing
December 2020

EUS in the diagnosis of pathologically undiagnosed esophageal tuberculosis.

BMC Gastroenterol 2020 Aug 28;20(1):291. Epub 2020 Aug 28.

Department of Gastroenterology, Affiliated Hospital, Zunyi Medical University, Zunyi, 563003, China.

Background: Esophageal tuberculosis (ET) is relatively rare, and the diagnosis is challenging. The aim of this study was to evaluate the clinical features of ET and highlight the role of endoscopic ultrasonography (EUS) in the diagnosis of pathologically undiagnosed ET.

Methods: We retrospectively analysed the clinical features, radiological performances, conventional endoscopic appearances, EUS features, treatment and outcomes of pathologically undiagnosed ET between January 2011 and December 2018. All 9 patients failed to be diagnosed by at least two repeated biopsies (such as routine biopsy, multipoint or deep biopsy, and even or EUS-guided fine-needle aspiration (EUS-FNA)).

Results: Nine patients (66.7% female) with a mean age of 45 years (range 29-59) complained of retrosternal pain or discomfort, or (and) dysphagia. Esophagoscopy demonstrated protruding lesions in the mucosa with central ulcers or erosion in five patients, submucosal bulges with smooth surfaces in one patient, submucosal bulges with diverticula in one patient, ulcers with suspicious fistula formation in one patient, and multiple ulcers in one patient. None of the patients received confirmed histopathological or bacteriological diagnoses by repeated biopsies. However, they were first suspected to have ET based on EUS examination. Because EUS found some characteristic ultrasonographic changes, which were very helpful for the diagnosis of ET when combined with clinical manifestations, the patients subsequently received diagnostic antituberculosis therapy. Finally, the patients recovered or improved with follow-up times ranging from 3 to 10 months.

Conclusions: EUS could help in the diagnosis of ET on basis of EUS features like poorly defined esophageal wall structure, enlarged paraesophageal or mediastinal lymph nodes, hypoechoic lesions of esophageal wall that are linked to the enlarged paraesophageal lymph nodes. However all attempts should be made to obtain histological or microbiological diagnosis.
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http://dx.doi.org/10.1186/s12876-020-01432-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7455903PMC
August 2020

Microchip with Single-Cell Impedance Measurements for Monitoring Osteogenic Differentiation of Mesenchymal Stem Cells under Electrical Stimulation.

Anal Chem 2020 09 28;92(18):12579-12587. Epub 2020 Aug 28.

State Key Laboratory of Precision Measurements Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing 100084, China.

Effective induction methods and monitoring are essential for studying the mechanism of biological responses in stem cell differentiation. This article proposes an induction method incorporating electrical stimulation under an inhomogeneous field with single-cell impedance monitoring for studying osteogenic differentiation of mesenchymal stem cells (MSCs) using a microchip. The microchip contains an array of sextupole-electrode units for implementing a combination of controllable electrical stimulation and single-cell impedance measurements. MSCs are inducted to osteogenic differentiation under electrical stimulation using quadrupole electrodes and single-cell impedances are monitored using a pair of microelectrodes at each unit center. The proposed microchip adopts an array design to monitor a number of MSCs in parallel, which improves measurement throughput and facilitates to carry out statistic tests. We perform osteogenic differentiation of MSCs on the microchip with and without electrical stimulation meanwhile monitoring single-cell impedance in real time for 21 days. The recorded impedance results show the detailed characteristic change of MSCs at the single-cell level during osteogenic differentiation, which demonstrates a significant difference between the conditions with and without electrical stimulation. The cell morphology and various staining analyses are also used to validate osteogenesis and correlate with the impedance expression. Correlation analysis of the impedance measurement, cell morphology, and various staining assays proves the great acceleration effect of the proposed electrical stimulation on osteogenic differentiation of MSCs. The proposed impedance method can monitor the dynamic process of cell development and study heterogeneity of stem cell differentiation at the single-cell level.
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http://dx.doi.org/10.1021/acs.analchem.0c02556DOI Listing
September 2020

Biomechanical Effects of Two Forms of PGF2α on Ex-vivo Rabbit Cornea.

Curr Eye Res 2021 Apr 11;46(4):452-460. Epub 2020 Sep 11.

School of Engineering, University of Liverpool, Liverpool, UK.

Purpose: To investigate the biomechanical effects of two synthetic prostaglandin F2α analogues (PGF2α), namely Travoprost and Tafluprost, on the ex-vivo rabbit cornea.

Materials And Methods: Ninety-six eyes of 48 Japanese white rabbits were divided into 3 equal groups randomly; the Travoprost treated group (Tra), the Tafluprost treated group (Taf) and the control group (Co). Eyes in Tra and Taf groups were preserved in storage medium for 10 days with 1:10 Travoprost and Tafluprost diluents, respectively; while the Co eyes were preserved in a similar but PGF2α-free medium. Twenty-four corneas of each group were tested under inflation conditions with up to 30 mmHg posterior pressure. The pressure-deformation data obtained experimentally were used in an inverse analysis process to derive the stress-strain behavior of the tissue, using which the tangent modulus, a direct measure of the tissue's material stiffness, was calculated. The remaining eight specimens of each group were analyzed using electron microscopy for fibril diameter and interfibrillar spacing.

Results: Although the central corneal thickness increased significantly in the three groups after storage ( < .01), it was similar in all groups both before ( = .598) and after storage ( = .181). After treatment with Travoprost and Tafluprost, the corneas exhibited lower tangent modulus (by 29.2% and 29.8%, respectively, at 6 kPa stress) and larger stromal interfibril spacing (by 21.9% and 23.6%) compared with the control group. There was no significant change in fibril diameter with either Travoprost or Tafluprost treatment ( = .769).

Conclusions: The results demonstrated significant reductions in tangent modulus and increases in interfibrillar spacing, which were of similar magnitudes, with the application of two different forms of PGF2α.
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http://dx.doi.org/10.1080/02713683.2020.1805771DOI Listing
April 2021

Predictive Value of Red Blood Cell Distribution Width in Chronic Obstructive Pulmonary Disease Patients with Pulmonary Embolism.

Anal Cell Pathol (Amst) 2020 21;2020:1935742. Epub 2020 Jul 21.

Department of Respiratory Medicine, The Huaian Clinical College of Xuzhou Medical University, Huaian 223001, China.

Purpose: This study is aimed at investigating the relationship between red cell distribution width (RDW) and chronic obstructive pulmonary disease (COPD) patients with pulmonary embolism (PE).

Methods: We conducted a retrospective study enrolling a total of 125 patients from January 2013 to December 2019. The study group consisted of 40 COPD patients with PE, and the control group had 85 COPD patients without PE. Clinical data including demographic characteristics, comorbidities, and results of imaging examinations and laboratory tests were recorded. Blood biomarkers, including red blood cell distribution width standard deviation (RDW-SD), red blood cell distribution width coefficient of variation (RDW-CV), and D-Dimer, were included.

Results: RDW-SD and RDW-CV were higher in the COPD patients with the PE group ( < 0.001). A higher RDW-SD led to a significantly increased risk of PE than a lower RDW-SD (adjusted odds ratio (OR): 1.188; 95% confidence interval (CI): 1.048-1.348). The area under the curve (AUC) of RDW-SD used for predicting PE was 0.737. Using 44.55 as the cutoff value of RDW-SD, the sensitivity was 80% and the specificity was 64.7%. The prediction accuracy of RDW-SD combined with D-Dimer (AUC = 0.897) was higher than that of RDW-SD or D-Dimer alone. The optimal cutoff value of RDW-SD+D-Dimer for predicting PE was 0.266, which generated a sensitivity of 87.5% and specificity of 83.5%.

Conclusion: RDW is significantly increased in COPD patients with PE and may thus be useful in predicting the occurrence of PE in patients with COPD.
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http://dx.doi.org/10.1155/2020/1935742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7391120PMC
July 2020

Does Acupuncture Benefit Delayed-Onset Muscle Soreness After Strenuous Exercise? A Systematic Review and Meta-Analysis.

Front Physiol 2020 17;11:666. Epub 2020 Jul 17.

School of Sports Science, Wenzhou Medical University, Wenzhou, China.

This systematic review and meta-analysis was designed to evaluate the effects of acupuncture intervention on alleviating delayed onset of muscle soreness (DOMS) after intense exercise. Randomized controlled trials (RCTs) were searched from online databases including Medline (PubMed), Cochrane Library, Web of Science, Embase, PsycINFO, China Knowledge Resource Integrated Database (CNKI), and Wanfang (Chinese) up to April 2019. Data points were extracted from the eligible RCTs at the time points of 24, 48, and 72 h post strenuous exercise-induced DOMS. The outcomes of muscle soreness rating (MSR), creatine kinase (CK), and maximal isometric force (MIF) were pooled into the meta-analysis to assess the acupuncture intervention on DOMS. Six eligible RCTs were included in the meta-analysis, and the results showed that acupuncture intervention significantly decreased MSR [standardized mean difference (SMD) -0.49, 95%CI -0.73 to -0.24, < 0.001, = 34%] and the serum level of CK (SMD -0.91, 95%CI -1.27 to -0.56, < 0.001, = 30%), accompanied with the improvement of the muscle strength (MIF) (SMD 0.54, 95%CI 0.16 to 0.93, = 0.006, = 51%) after intense exercise. At the same time, the findings also revealed that acupuncture intervention had a long-lasting effect and tended to accumulate the effect size and that it had the most efficacy on alleviating DOMS at the time point of 72 h post exercise. The current evidence indicates that acupuncture intervention after intense exercise could be effective for alleviating DOMS and improving muscle recovery. The long-lasting effect of acupuncture intervention on DOMS started from 24 h and would reach a peak on the time point of 72 h post exercise.
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http://dx.doi.org/10.3389/fphys.2020.00666DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379881PMC
July 2020

Effect of Furnace Gas Composition on Characteristics of Supersonic Oxygen Jets in the Converter Steelmaking Process.

Materials (Basel) 2020 Jul 28;13(15). Epub 2020 Jul 28.

School of Metallurgical and Ecological Engineering, University of Science and Technology Beijing, Beijing 100083, China.

During the converter steelmaking process, the presence of supersonic oxygen jets can provide oxygen to high-temperature metal baths that promotes chemical reactions in the bath, accelerates the smelting rhythm, and facilitates a uniform distribution of the ingredients in the bath. In this paper, a computational fluid dynamics (CFD) model with combustion reactions is established and compared to the results of combustion experiment. This paper studies the behavior and fluid flow characteristics of supersonic oxygen jets under different environmental compositions under a steelmaking temperature of 1873 K. This validated CFD model can be used to investigate the effect of furnace gas on supersonic oxygen jet characteristics during the converter steelmaking process. The results indicate that the composition of furnace gas has an impact on the characteristics of the oxygen jet. Specifically, as the carbon monoxide (CO) volume fraction increases, the high velocity region of supersonic oxygen jet increases, and the high temperature and the high turbulent kinetic energy regions expand.
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http://dx.doi.org/10.3390/ma13153353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7436270PMC
July 2020

Allosterically Linked Binding Sites in Serotonin Transporter Revealed by Single Molecule Force Spectroscopy.

Front Mol Biosci 2020 3;7:99. Epub 2020 Jun 3.

Institute of Biophysics, Johannes Kepler University Linz, Linz, Austria.

Crystal structures and experiments relying on the tools of molecular pharmacology reported conflicting results on ligand binding sites in neurotransmitter/sodium symporters (NSS). We explored the number and functionality of ligand binding sites of NSS in a physiological setting by designing novel tools for atomic force microscopy (AFM). These allow for directly measuring the interaction forces between the serotonin transporter (SERT) and the antidepressant S-citalopram (S-CIT) on the single molecule level: the AFM cantilever tips were functionalized with S-CIT via a flexible polyethylene glycol (PEG) linker. The tip chemistry was validated by specific force measurements and recognition imaging on CHO cells. Two distinct populations of characteristic binding strengths of S-CIT binding to SERT were revealed in Na-containing buffer. In contrast, in Li-containing buffer, SERT showed only low force interactions. Conversely, the vestibular mutant SERT-G402H merely displayed the high force population. These observations provide physical evidence for the existence of two binding sites in SERT. The dissociation rate constant of both binding sites was extracted by varying the dynamics of the force-probing experiments. Competition experiments revealed that the two sites are allosterically coupled and exert reciprocal modulation.
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http://dx.doi.org/10.3389/fmolb.2020.00099DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7325972PMC
June 2020

Catching Common Cold Virus with a Net: Pyridostatin Forms Filaments in Tris Buffer That Trap Viruses-A Novel Antiviral Strategy?

Viruses 2020 07 4;12(7). Epub 2020 Jul 4.

Vienna Biocentre, Max Perutz Laboratories, Medical University of Vienna, Center of Med. Biochemistry, Dr. Bohr Gasse 9/3, A-1030 Vienna, Austria.

The neutrophil extracellular trap (ET) is a eukaryotic host defense machinery that operates by capturing and concentrating pathogens in a filamentous network manufactured by neutrophils and made of DNA, histones, and many other components. Respiratory virus-induced ETs are involved in tissue damage and impairment of the alveolar-capillary barrier, but they also aid in fending off infection. We found that the small organic compound pyridostatin (PDS) forms somewhat similar fibrillary structures in Tris buffer in a concentration-dependent manner. Common cold viruses promote this process and become entrapped in the network, decreasing their infectivity by about 70% in tissue culture. We propose studying this novel mechanism of virus inhibition for its utility in preventing viral infection.
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http://dx.doi.org/10.3390/v12070723DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7412420PMC
July 2020

Improved anaerobic digestion efficiency of high-solid sewage sludge by enhanced direct interspecies electron transfer with activated carbon mediator.

Bioresour Technol 2020 Oct 8;313:123648. Epub 2020 Jun 8.

Department of Grain Science and Industry, Kansas State University, 101C BIVAP, 1980 Kimball Avenue, Manhattan, KS 66506, USA.

High-solid anaerobic digestion (AD) faces the problems of easy acidification and low methane production efficiency. In this study, activated carbon (AC)-enhanced direct interspecies electron transfer (DIET) was investigated to overcome such problems. Results showed the conversion of volatile fatty acids (VFAs) into methane rate was increased with AC addition, which led improved methane production efficiency. The methane yields from the early AD stage improved by 124.0-146.3% with AC addition. The T shortened by 8-9 days with AC addition. The relative abundances of Geobacter, Syntrophomonas and Methanosaeta that associated with DIET improved for 63.65%, 256.3% and 4.35% by AC addition, which reflected the enhanced DIET with AC addition. The redox activity of AC might be responsible for the enhanced DIET. This study would advance the understanding of DIET and provide a potential solution to the problems existed in high-solid AD.
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http://dx.doi.org/10.1016/j.biortech.2020.123648DOI Listing
October 2020

Influence of Desulfurization with FeO on the Reduction of Nickel Converter Slag.

Materials (Basel) 2020 May 25;13(10). Epub 2020 May 25.

School of Minerals Processing and Bioengineering, Central South University, Changsha 410083, China.

Generally in the nickel converter slag, metals are mainly in the form of sulfides, which are difficult to separate from slag. Although metal oxides in the slag, such as NiO, CoO, and CuO, are easily reduced into metal using carbon, the presence of sulfur inhibits the reduction reaction. In this study, the addition of FeO to nickel converter slag produced desulfurized slag, which enhanced the carbothermal reduction process. Increasing the desulfurization rate promoted the conversion of sulfides into oxides in slag, which significantly increased the activity of NiO, CuO, and FeO. However, the residual sulfur content had no significant effect on the activity of FeO and CoO, due to the high initial FeO content and cobalt existing mainly in the form of oxides. The optimum addition of FeO was 15.0 g per 100 g nickel slag, while the desulfurization ratio was 36.84% and the rates of nikel, cobalt and copper recovery were 95.33%, 77.73%, and 73.83%, respectively.
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http://dx.doi.org/10.3390/ma13102423DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7288285PMC
May 2020

Light-Switchable Yolk-Mesoporous Shell UCNPs@MgSiO for Nitric Oxide-Evoked Multidrug Resistance Reversal in Cancer Therapy.

ACS Appl Mater Interfaces 2020 Jul 28;12(27):30066-30076. Epub 2020 Jun 28.

MOE Key Laboratory for Analytical Science of Food Safety and Biology, State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University, Fuzhou, Fujian 350116, China.

Gas therapy has emerged as a forceful strategy for augmenting the effects of chemotherapeutic drugs against cancer cells. However, it remains extremely challenging to effectively deliver gas into tissues of interest and unravel its underlying mechanisms. Herein, we designed a near-infrared (NIR) light-switchable nitric oxide (NO) delivery nanosystem for high-efficacy multidrug resistance (MDR) reversal in cancer therapy based on a yolk-shell upconverting nanoparticles@magnesium silica (UCNP@MgSiO). The internal hollow cavity and flower-like mesoporous shell of UCNPs@MgSiO not only enabled a significantly high encapsulation capacity for the NO precursor (BNN6) and doxorubicin (DOX) but also allowed the enhanced cellular uptake, resulting in NIR-triggered NO generation and low pH-triggered DOX release in cancer cells. Mechanistically, intracellular NO can downregulate the drug efflux-related P-glycoprotein and adenosine 5'-triphosphate-binding cassette transporters, thereby increasing the DOX accumulation in the cell nuclei. Such combination therapy of NO and DOX induced the apoptosis of MDR cells and completely inhibited in vivo MDR tumor growth. We further elucidated the therapy mechanism via proteomic profiling, showcasing the downregulation of the ubiquitin-proteasome pathway and nuclear factor kappa-B signaling pathway in the NO-treated MDR cells. Therefore, our findings develop a promising nanoscale gas/drug delivery paradigm for fighting MDR tumors and providing molecular insights into cancer therapy.
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http://dx.doi.org/10.1021/acsami.0c06102DOI Listing
July 2020