Publications by authors named "Ce Zhang"

233 Publications

Support Vector Machine Classifier via L Soft-Margin Loss.

IEEE Trans Pattern Anal Mach Intell 2021 Jun 24;PP. Epub 2021 Jun 24.

Support vector machines (SVM) have drawn wide attention for the last two decades due to its extensive applications, so a vast body of work has developed optimization algorithms to solve SVM with various soft-margin losses. To distinguish all, in this paper, we aim at solving an ideal soft-margin loss SVM: L soft-margin loss SVM (dubbed as L-SVM). Many of the existing (non)convex soft-margin losses can be viewed as one of the surrogates of the L soft-margin loss. Despite its discrete nature, we manage to establish the optimality theory for the L-SVM including the existence of the optimal solutions, the relationship between them and P-stationary points. These not only enable us to deliver a rigorous definition of L support vectors but also allow us to define a working set. Integrating such a working set, a fast alternating direction method of multipliers is then proposed with its limit point being a locally optimal solution to the L-SVM. Finally, numerical experiments demonstrate that our proposed method outperforms some leading classification solvers from SVM communities, in terms of faster computational speed and a fewer number of support vectors. The bigger the data size is, the more evident its advantage appears.
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http://dx.doi.org/10.1109/TPAMI.2021.3092177DOI Listing
June 2021

Scanning Electron Microscopic Assessment of Stent Coating Integrity in Jailed Wire Technique for Bifurcation Treatment.

J Interv Cardiol 2021 24;2021:2629393. Epub 2021 May 24.

Coronary Heart Disease Center, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.

Objectives: To assess the impact of different guidewires on stent coating integrity in jailed wire technique (JWT) for bifurcation treatment.

Background: JWT is commonly adopted to protect side branch in provisional one-stent strategy for coronary bifurcation lesions. However, this technique may cause defects in stent coatings. The degree of coating damage caused by different types of jailed wires remains unknown.

Methods: A fluid model with a bifurcation was established to mimic the condition in vivo. One-stent strategy was performed with three types of guidewire (nonpolymer-jacketed wire, intermediate polymer-jacketed wire, and full polymer-jacketed wire) tested for JWT. Scanning electron microscopy (SEM) was used to evaluate stent coating integrity and wire structure. The degrees of coating defects were recorded as no, slight, moderate, and severe defects.

Results: A total of 27 samples were tested. Analyses of SEM images showed a significant difference in the degree of coating damage among the three types of wire after the procedure of JWT ( < 0.001). Nonpolymer-jacketed wire could inevitably cause a severe defect in stent coatings, while full polymer-jacketed wire caused the least coating damages. Besides, there were varying degrees of coil deformation in nonpolymer-jacketed wires, while no surface damage or jacket shearing was observed in full polymer-jacketed wires.

Conclusions: Although nonpolymer-jacketed wire has long been recommended for JWT, our bench-side study suggests that full polymer-jacketed wire may be a better choice. Further clinical studies are needed to confirm our findings.
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http://dx.doi.org/10.1155/2021/2629393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8166474PMC
May 2021

Relationship Between High-Sensitivity C-Reactive Protein and Long-Term Outcomes in Elderly Patients With 3-Vessel Disease.

Angiology 2021 Jun 10:33197211021195. Epub 2021 Jun 10.

34736Fuwai Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People's Republic of China.

The prognostic value of high-sensitivity C-reactive protein (hsCRP) in complex coronary artery disease has not been fully established. We aimed to determine the association between hsCRP and long-term outcomes in elderly patients with 3-vessel disease (TVD). From April 2004 to February 2011, 3069 patients aged ≥65 years with TVD were consecutively enrolled and received medical treatment alone, percutaneous coronary intervention, or coronary artery bypass grafting. The patients were divided into 2 groups according to their hsCRP levels: <3.00 mg/L (62.1%) and ≥3.00 mg/L (37.9%). The mean age was 71 ± 4 years. The high hsCRP group had more risk factors and more frequently received conservative treatment than the low hsCRP group. During a median follow-up period of 6.2 years, elevated hsCRP was significantly associated with increased all-cause death (19.5% vs 29.6%, < .001), cardiac death (9.4% vs 15.2%, = .001), and major adverse cardiovascular and cerebrovascular events (34.1% vs 42.5%, = .001). Multivariable Cox regression analyses revealed that hsCRP was an independent predictor for all of these events. Combining hsCRP with Synergy between PCI with TAXUS and Cardiac Surgery score II further improved the predictive power of the score. The relationship between hsCRP and mortality was relatively consistent across subgroups. Overall, hsCRP could prove useful for risk prediction in elderly patients.
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http://dx.doi.org/10.1177/00033197211021195DOI Listing
June 2021

LuxQ-LuxU-LuxO pathway regulates biofilm formation by Vibrio parahaemolyticus.

Microbiol Res 2021 May 27;250:126791. Epub 2021 May 27.

Department of Marine Biology, College of Oceanography, Hohai University, Nanjing, Jiangsu, China. Electronic address:

Vibrio parahaemolyticus, a common foodborne pathogen, can form biofilms for survival in various environments and for bacterial transmission. Lux systems in Vibrio species are the typical two-component signal transduction systems, which have been demonstrated to contribute to various phenotypes; however, the functions of each homolog of the Lux system in V. parahaemolyticus in the regulation of biofilm formation remain largely unknown. In this study, we first showed that LuxQ, LuxU, and LuxO are essential for controlling biofilm formation by V. parahaemolyticus, through gene knockout studies. We also found that they acted in the same signaling pathway and their deletion mutants exhibited a similar level of biofilm formation. Furthermore, site-directed mutagenesis revealed that the conserved residues for phosphorylation in LuxQ (D784), LuxU (H56) and LuxO (D47) were critical for their regulatory functions on biofilm formation. Phos-tag™ sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed the phosphorylation of LuxU and LuxQ in vivo. Finally, qPCR analysis displayed that the three mutants had a significant decrease in the transcription level of cps loci and cpsQ compared with the wild type strain, which is consistent with the observed phenotype of biofilm formation. Therefore, we propose that LuxQ and its downstream factors LuxU and LuxO function in the same signaling cascade to control biofilm formation by regulating the expression of cpsQ and cps loci. The results of this study provide new data regarding the role of the LuxQ-LuxU-LuxO pathway in biofilm formation by V. parahaemolyticus and help further understand the complex regulatory functions of Lux pathways.
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http://dx.doi.org/10.1016/j.micres.2021.126791DOI Listing
May 2021

Does Percutaneous Coronary Intervention on Off Days have an Effect on Long-term Prognosis in Patients with Coronary Artery Disease in China?

Biomed Environ Sci 2021 May;34(5):387-394

Department of Cardiology, Fuwai Hospital, Chinese Academy of Medical Sciences, Beijing 100037, China.

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http://dx.doi.org/10.3967/bes2021.051DOI Listing
May 2021

Dynamic intracellular mechanical cues facilitate collective signaling responses.

iScience 2021 May 3;24(5):102396. Epub 2021 Apr 3.

State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University, Xi'an 710069, China.

Collective behavior emerges in diverse life machineries, e.g., the immune responses to dynamic stimulations. The essential questions that arise here are that whether and how cells collectively respond to stimulation frequencies higher than their intrinsic natural values, e.g., the acute inflammation conditions. In this work, we systematically studied morphological and signaling responses of population fibroblasts in an interconnected cell monolayer and uncovered that, besides the natural NF-B oscillation frequency of 1/90 min, collective signaling response emerges in the cell monolayer at 1/20 min TNF- input periodicity as well. Using a customized microfluidic device, we independently induced dynamic chemical stimulation and cytoskeleton reorganization on the stand-alone cells to exclude the effect of cell-cell communication. Our results reveal that, at this particular frequency, chemical stimulation is translated into dynamic intracellular mechanical cues through RAC1-medicated induction of dynamic cell-cell connections and cytoskeleton reorganizations, which synergize with chemical input to facilitate collective signaling responses.
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http://dx.doi.org/10.1016/j.isci.2021.102396DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091894PMC
May 2021

Generation of Dynamical Environmental Conditions using a High-Throughput Microfluidic Device.

J Vis Exp 2021 04 17(170). Epub 2021 Apr 17.

State Key Laboratory of Cultivation Base for Photoelectric Technology and Functional Materials, State Key Laboratory of Photon-Technology in Western China Energy, Institute of Photonics and Photon-Technology, Northwest University;

Mimicking in vivo environmental conditions is crucial for in vitro studies on complex life machinery. However, current techniques targeting live cells and organs are either highly expensive, like robotics, or lack nanoliter volume and millisecond time accuracy in liquid manipulation. We herein present the design and fabrication of a microfluidic system, which consists of 1,500 culture units, an array of enhanced peristaltic pumps and an on-site mixing modulus. To demonstrate the capacities of the microfluidic device, neural stem cell (NSC) spheres are maintained in the proposed system. We observed that when the NSC sphere is exposed to CXCL in day 1 and EGF in day 2, the round-shaped conformation is well maintained. Variation in the input order of 6 drugs causes morphological changes to the NSC sphere and the expression level representative marker for NSC stemness (i.e., Hes5 and Dcx). These results indicate that dynamic and complex environmental conditions have great effects on NSC differentiation and self-renewal, and the proposed microfluidic device is a suitable platform for high throughput studies on the complex life machinery.
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http://dx.doi.org/10.3791/61735DOI Listing
April 2021

SLC40A1 Mediates Ferroptosis and Cognitive Dysfunction in Type 1 Diabetes.

Neuroscience 2021 05 13;463:216-226. Epub 2021 Mar 13.

Department of Physiology, Shanxi Medical University, Taiyuan, Shanxi 030001, PR China. Electronic address:

Cognitive dysfunction often accompanies diabetes. Both hypoglycemia and hyperglycemia cause cognitive dysfunctions. However, the underlying pathophysiology remains unclear. Recent evidence show that ferroptosis primarily triggers nerve cell death, Alzheimer's disease (AD), Huntington's disease (HD), and Parkinson's disease (PD). The present study aimed to investigate whether ferroptosis is a vital pathogenic pathway in diabetes-induced cognitive dysfunction. Type 1 diabetic rat model was created by intraperitoneal injection of streptozotocin (STZ). Significant cognitive dysfunction was observed in the diabetic rats as evidenced by increase in latency period to find a hidden platform and decreased cumulative time spent in the target quadrant (TQ) in the Morris water maze test. We detected the amplitude of low-frequency fluctuation (ALFF) of the BOLD (Blood Oxygenation Level-Dependent) signal using resting-state functional magnetic resonance imaging (rs-fMRI). Consequently, we found that the ALFF values, as well as the T2 relaxation time of the bilateral hippocampus, were reduced in Type 1 diabetic rats. We detected Fe level and lipid peroxidation products (malondialdehyde (MDA) and 4-Hydroxynonenal (4-HNE)) in the hippocampus. Mitochondria and neuron injury in the STZ-induced diabetic rats were determined using a Transmission Electron Microscope and Nissl body staining. Iron overload and ferroptosis were detected in the hippocampus. Furthermore, mRNA microarray analysis revealed 201 dysregulated mRNAs in STZ-induced type 1 diabetes (T1D). Pathway enrichment analyses indicated that differentially expressed mRNAs associated-coding genes were associated with ferroptosis. Among ferroptosis signaling pathway genes, Slc40a1 gene (ferroportin) was downregulated. We show that ferroptosis is associated with diabetic cognitive dysfunction and Slc40a1 mediates ferroptosis in T1D.
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http://dx.doi.org/10.1016/j.neuroscience.2021.03.009DOI Listing
May 2021

Sub-chronic exposure to ammonia inhibits the growth of juvenile Wuchang bream (Megalobrama amblycephala) mainly by downregulation of growth hormone/insulin-like growth factor axis.

Environ Toxicol 2021 Jun 15;36(6):1195-1205. Epub 2021 Mar 15.

College of Fisheries, Huazhong Agricultural University, Wuhan, China.

In this study, healthy Wuchang bream (Megalobrama amblycephala) juveniles were exposed to 0, 5, 10, 20 and 30 mg/L total ammonia nitrogen for 30 days to elucidate toxic effects and mechanisms of ammonia on growth performance involved with the regulation of growth hormone/insulin-like growth factor (GH/IGF) and hypothalamic-pituitary-thyroid (HPT) axes. Our results showed that the increasing total ammonia nitrogen concentrations caused dose-depend decreases in the weight gain and specific growth rate but increases in the food conversion ratio and mortality in juvenile bream, indicating growth inhibitory effects induced by ammonia. Concurrently, GH, IGF-1 at protein and mRNA levels were significantly decreased in ammonia exposure groups (p < .05), while serum thyroid stimulating hormone, free thyroxine, free triiodothyronine levels were significantly reduced only in fish exposed to higher concentrations of 20 and 30 mg/L ammonia (p < .05), suggesting that ammonia exposure could perturb both GH/IGF-axis and HPT-axis functions. Furthermore, transcriptional levels of extracellular regulated protein kinases 2 (erk2), phosphatidylinositol 3-kinase (pi3k), protein kinase B (akt), target of rapamycin (tom) and ribosomal protein S6 kinase-polypeptide 1(s6k1) in the dorsal muscle were significantly down-regulated in the fish exposed to ammonia (p < .05). This fact indicated that MAPK/ERK pathway and PI3K/AKT pathway should be responsible for the growth inhibition. Combining the results of spearman correlation coefficient, it should be noted that the GH/IGF axis played a more important role in regulating the growth than the HPT axis in Wuchang bream under persistent ammonia stress.
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http://dx.doi.org/10.1002/tox.23118DOI Listing
June 2021

EEG-inception: an accurate and robust end-to-end neural network for EEG-based motor imagery classification.

J Neural Eng 2021 Mar 10. Epub 2021 Mar 10.

Mechanical Engineering, Virginia Polytechnic Institute and State University, 635 Prices Fork Rd, Blacksburg, Virginia, 24060, UNITED STATES.

Classification of EEG-based motor imagery (MI) is a crucial non-invasive application in brain-computer interface (BCI) research. This paper proposes a novel convolutional neural network (CNN) architecture for accurate and robust EEG-based MI classification that outperforms the state-of-the-art methods. The proposed CNN model, namely EEG-Inception, is built on the backbone of the Inception-Time network, which has showed to be highly efficient and accurate for time-series classification. Also, the proposed network is an end-to-end classification, as it takes the raw EEG signals as the input and does not require complex EEG signal-preprocessing. Furthermore, this paper proposes a novel data augmentation method for EEG signals to enhance the accuracy, at least by 3%, and reduce overfitting with limited BCI datasets. The proposed model outperforms all state-of-the-art methods by achieving the average accuracy of 88.4% and 88.6% on the 2008 BCI Competition IV 2a (four-classes) and 2b datasets (binary-classes), respectively. Furthermore, it takes less than 0.025 seconds to test a sample suitable for real-time processing. Moreover, the classification standard deviation for nine different subjects achieves the lowest value of 5.5 for the 2b dataset and 7.1 for the 2a dataset, which validates that the proposed method is highly robust. From the experiment results, it can be inferred that the EEG-Inception network exhibits a strong potential as a subject-independent classifier for EEG-based MI tasks.
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http://dx.doi.org/10.1088/1741-2552/abed81DOI Listing
March 2021

Decidual-derived RANKL facilitates macrophages accumulation and residence at the maternal-fetal interface in human early pregnancy.

Am J Reprod Immunol 2021 Feb 24:e13406. Epub 2021 Feb 24.

Center for Human Reproduction and Genetics, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, China.

Problem: During the first trimester, the accumulation of macrophages, which is the second largest decidual leukocyte population (~20%) at the maternal-fetal interface, is quite vital for a successful pregnancy, including embryo implantation, trophoblast invasion, and vascular remodeling. The mechanism of the enrichment and redistribution of macrophages in the uterine decidua of early pregnancy is largely unclear.

Method Of Study: A total of 37 women with normal early pregnancies were included. Primary decidual macrophages (dMφs) (n = 37) and primary decidual stromal cells (DSCs) (n = 37) were isolated, and the adhesion molecules were analyzed by flow cytometry (FCM). Adhesive experiment was carried out to evaluate the adhesion capacity by counting cell numbers of dMφs adhered to DSCs in a co-culture system.

Results: We found that RANK dMφs was the dominating subtype at the maternal-fetal interface. The expression of adhesion molecules (eg, CD29, CD31, CD54, and CD62L) on the surface of RANK dMφs was higher than that of RANK dMφs. After co-culture with DSCs, the expression of adhesion molecules on dMφs was up-regulated in a RANKL-dependent manner. Meanwhile, dMφs promoted the releasing of RANKL on DSCs after co-culture. Consistently, dMφs exhibited the lessoned capacity of adhesion to DSCs when blocking the crosstalk of RANKL-RANK between the DSCs and dMφs in vitro.

Conclusion: These results suggest that the interaction of RANKL-RANK up-regulates the expression of adhesion molecules on the surface of dMφs, contributing to the accumulation and residence of dMφs in human early pregnancy.
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http://dx.doi.org/10.1111/aji.13406DOI Listing
February 2021

Synthesis of a novel amphoteric copolymer and its application as a dispersant for coal water slurry preparation.

R Soc Open Sci 2021 Jan 13;8(1):201480. Epub 2021 Jan 13.

Shaanxi Key Laboratory of Chemical Additives for Industry, Shaanxi University of Science and Technology, Xi'an 710021, People's Republic of China.

In this work, a novel amphoteric copolymer named Poly(sodium p-styrenesulfonate--acrylic acid--diallyldimethylammonium chloride) (P(SS--AA--DMDAAC)) was synthesized via free radical polymerization. Afterwards, P(SS--AA--DMDAAC) was explored for use as a dispersant in coal water slurry (CWS) preparation. The structure of P(SS--AA--DMDAAC) was verified by Fourier transform infrared spectroscopy and nuclear magnetic resonance. The synthetic conditions were optimized as the feed ratio of AA to SS was 1 : 1 (for Yulin coal) or 1.5 : 1 (for Yili coal), and DMDAAC dosage was 4.0 wt% (for Yulin coal) and 6.0 wt% (for Yili coal) toward total monomers. The performances of P(SS--AA--DMDAAC) as a dispersant for CWS were evaluated by various technologies, such as apparent viscosity, zeta potential, static stability and contact angle measurements. The results revealed that the optimized dosage of P(SS--AA--DMDAAC) in CWS preparation was 0.3 and 0.4 wt% for Yulin coal and Yili coal respectively. In this optimum condition, CWS prepared using P(SS--AA--DMDAAC) as dispersant showed a typical shear thinning behaviour and excellent stability, which are desired in industries. The rheological models also confirmed the pseudo-plastic characteristics of CWS. Finally, compared with the widely used anionic dispersant naphthalene sulphonate formaldehyde condensate (NSF) and poly(sodium p-styrenesulfonate) (PSS), P(SS--AA--DMDAAC) developed in this work exhibited better slurry making performance. The introduction of cationic functional groups promoted the adsorption of the dispersant, which further enhanced the electrostatic repulsion and steric hindrance among coal particles. Accordingly, the viscosity of CWS decreased and static stability enhanced.
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http://dx.doi.org/10.1098/rsos.201480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7890484PMC
January 2021

Asymmetric pathological pachymeningeal enhancement: A new imaging feature for cerebral venous thrombosis.

Clin Neurol Neurosurg 2021 Mar 27;202:106516. Epub 2021 Jan 27.

Department of Radiology, the Second Hospital of Dalian Medical University, Dalian City, Liaoning Province, China. Electronic address:

Purpose: Cerebral venous thrombosis (CVT) has various clinical presentations and has a median onset delay of 7 days. So it is important to find more identifiable early imaging manifestations for CVT.

Method: This was a retrospective study. Patients with CVT (CVT group, n = 26) diagnosed by conventional imaging techniques (magnetic resonance imaging and/or digital subtraction angiogram) and patients with symptomatic intracranial atherosclerosis (control group, n = 30) were included. Magnetic resonance black-blood thrombus imaging (MRBTI) technique had been performed in both groups. The CVT group was divided into 3 groups based on the duration of clinical onset: ≤7 days (group 1), between 7 and 30 days (group 2), and >30 days (group 3). Pathological pachymeningeal enhancement and its characteristics were analyzed between the CVT group and the control group.

Results: Pathological pachymeningeal enhancement was found in 14 CVT patients (54 %) and none in control group (P value = 0.000). The bilateral pathological pachymeningeal enhancement was involved in 10 CVT patients, 6 patients were asymmetric, and 4 patients had ipsilateral enhancement. Asymmetric pathological pachymeningeal enhancement was 71 % and predominantly located on the thrombosed sinus side. Strong enhancement was found in the venous sinus wall beside the thrombus. Pathological pachymeningeal enhancement percentages of three subgroups were 75 % in group 1, 55 % in group 2, and 29 % in group 3 and had no statistical differences (p value = 0.198).

Conclusions: Current findings suggest asymmetrical pathological pachymeningeal enhancement was associated was CVT and may be a new imaging feature for CVT.
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http://dx.doi.org/10.1016/j.clineuro.2021.106516DOI Listing
March 2021

R-YOLO: A Real-Time Text Detector for Natural Scenes with Arbitrary Rotation.

Sensors (Basel) 2021 Jan 28;21(3). Epub 2021 Jan 28.

School of Remote Sensing and Information Engineering, Wuhan University, Wuhan 430079, China.

Accurate and efficient text detection in natural scenes is a fundamental yet challenging task in computer vision, especially when dealing with arbitrarily-oriented texts. Most contemporary text detection methods are designed to identify horizontal or approximately horizontal text, which cannot satisfy practical detection requirements for various real-world images such as image streams or videos. To address this lacuna, we propose a novel method called Rotational You Only Look Once (R-YOLO), a robust real-time convolutional neural network (CNN) model to detect arbitrarily-oriented texts in natural image scenes. First, a rotated anchor box with angle information is used as the text bounding box over various orientations. Second, features of various scales are extracted from the input image to determine the probability, confidence, and inclined bounding boxes of the text. Finally, Rotational Distance Intersection over Union Non-Maximum Suppression is used to eliminate redundancy and acquire detection results with the highest accuracy. Experiments on benchmark comparison are conducted upon four popular datasets, i.e., ICDAR2015, ICDAR2013, MSRA-TD500, and ICDAR2017-MLT. The results indicate that the proposed R-YOLO method significantly outperforms state-of-the-art methods in terms of detection efficiency while maintaining high accuracy; for example, the proposed R-YOLO method achieves an F-measure of 82.3% at 62.5 fps with 720 p resolution on the ICDAR2015 dataset.
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http://dx.doi.org/10.3390/s21030888DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865800PMC
January 2021

Metabolomics safety assessments of microcystin exposure via drinking water in rats.

Ecotoxicol Environ Saf 2021 Apr 30;212:111989. Epub 2021 Jan 30.

CAS Key Laboratory of Magnetic Resonance in Biological Systems, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, National Center for Magnetic Resonance in Wuhan, Wuhan Institute of Physics and Mathematics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (CAS), Wuhan 430071, China; Wuhan National Laboratory for Optoelectronics, Wuhan 430074, China. Electronic address:

Drinking water exposure to microcystin-leucine-arginine (MC-LR), the most widely occurring cyanotoxins, poses a highly potential risk for human health. However, the health risk of MC-LR exposure at current guideline value in drinking water has not yet entirely evaluated. In the current study, we used H NMR-based metabolomics combined with targeted metabolic profiling by GC/LC-MS to explore the toxic effects of MC-LR exposure at environmentally relevant concentrations via drinking water in rats. The results revealed that multiple biological consequences of MC-LR exposure on host metabolism in rats. Both relatively low and high doses of MC-LR used here induced hepatic lipogenesis and inflammation. While only relatively high dose MC-LR (10 μg/L) in drinking water caused more metabolic disorders including inhibition of gluconeogenesis and promotion of β-oxidation of fatty acid. Although the dose of 1.0 μg/L MC-LR is extremely low for rats, alterations of metabolic profiles were unexpectedly found in rat liver and serum, alarming potential health risk of MC-LR at the WHO guideline level.
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http://dx.doi.org/10.1016/j.ecoenv.2021.111989DOI Listing
April 2021

Lipin 1 deficiency causes adult-onset myasthenia with motor neuron dysfunction in humans and neuromuscular junction defects in zebrafish.

Theranostics 2021 1;11(6):2788-2805. Epub 2021 Jan 1.

Key laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Xi'an 710069, China.

Lipin 1 is an intracellular protein acting as a phosphatidic acid phosphohydrolase enzyme controlling lipid metabolism. Human recessive mutations in cause recurrent, early-onset myoglobinuria, a condition normally associated with muscle pain and weakness. Whether and how lipin 1 deficiency in humans leads to peripheral neuropathy is yet unclear. Herein, two novel compound heterozygous mutations in with neurological disorders, but no myoglobinuria were identified in an adult-onset syndromic myasthenia family. The present study sought to explore the pathogenic mechanism of in muscular and neural development. The clinical diagnosis of the proband was compared to the known 48 cases of recessive homozygous mutations. Whole-exome sequencing was carried out on the syndromic myasthenia family to identify the causative gene. The pathogenesis of lipin 1 deficiency during somitogenesis and neurogenesis was investigated using the zebrafish model. Whole-mount hybridization, immunohistochemistry, birefringence analysis, touch-evoke escape response and locomotion assays were performed to observe the changes in muscles and neurons. The conservatism of the molecular pathways regulated by lipin 1 was evaluated in human primary glioblastoma and mouse myoblast cells by siRNA knockdown, drug treatment, qRT-PCR and Western blotting analysis. The patient exhibited adult-onset myasthenia accompanied by muscle fiber atrophy and nerve demyelination without myoglobinuria. Two novel heterozygous mutations, c.2047A>C (p.I683L) and c.2201G>A (p.R734Q) in , were identified in the family and predicted to alter the tertiary structure of LPIN1 protein. Lipin 1 deficiency in zebrafish embryos generated by morpholino knockdown or human mutant mRNA injections reproduced the myotomes defects, a reduction both in primary motor neurons and secondary motor neurons projections, morphological changes of post-synaptic clusters of acetylcholine receptors, and myelination defects, which led to reduced touch-evoked response and abnormalities of swimming behaviors. Loss of lipin 1 function in zebrafish and mammalian cells also exhibited altered expression levels of muscle and neuron markers, as well as abnormally enhanced Notch signaling, which was partially rescued by the specific Notch pathway inhibitor DAPT. These findings pointed out that the compound heterozygous mutations in human caused adult-onset syndromic myasthenia with peripheral neuropathy. Moreover, zebrafish could be used to model the neuromuscular phenotypes due to the lipin 1 deficiency, where a novel pathological role of over-activated Notch signaling was discovered and further confirmed in mammalian cell lines.
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http://dx.doi.org/10.7150/thno.53330DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806489PMC
January 2021

Application of Conchal Cartilage Grafts in Nasal Tip Plasty: Comparison and Experience of 3 Methods.

Ann Plast Surg 2021 03;86(3S Suppl 2):S199-S207

From the Department of Plastic and Reconstructive Surgery, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, China.

Introduction: The autologous conchal cartilage of good elasticity is easy to harvest, thus is often used in nasal tip plasty of East Asians. However, the operation techniques vary a lot among different surgeons. This article aims to introduce 3 techniques commonly used in clinical practice.

Methods: One hundred three patients were included in this study and divided into 3 groups according to the shape of the nasal tip during 2017 to 2019. The patients were followed up for at least 6 months. All patients were measured with Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS). ImageJ software was used to measure and calculate the projection ratio for lateral position standard image, and columella-labial angle (CLA) was measured.

Results: In group 1, SCHNOS for nasal obstruction (SCHNOS-O) score were 13.23 ± 7.61 and 14.49 ± 10.55 (P > 0.05); SCHNOS for nasal cosmesis (SCHNOS-C) score were 66.55 ± 31.23 and 21.73 ± 18.91 (P < 0.001); projection ratio were 0.51 ± 0.04 and 0.57 ± 0.05 (P < 0.001); CLA were 91.02° ± 5.67° and 93.55° ± 4.64° (P > 0.05), preoperative and postoperative, respectively. In group 2, SCHNOS-O score were 16.76 ± 13.44 and 15.44 ± 9.26 (P > 0.05); SCHNOS-C score were 61.87 ± 44.14 and 19.16 ± 29.37 (P < 0.001); projection ratio were 0.50 ± 0.05 and 0.58 ± 0.03 (P < 0.001); CLA were 92.32° ± 6.39° and 94.86° ± 5.96°(P > 0.05), preoperative and postoperative, respectively. In group 3, SCHNOS-O score were 15.25 ± 7.83 and 17.73 ± 11.66 (P > 0.05); SCHNOS-C score were 52.03 ± 33.38 and 17.73 ± 11.66 (P < 0.001); projection ratio were 0.53 ± 0.05 and 0.57 ± 0.02 (P < 0.001); CLA were 91.65° ± 5.75° and 93.21° ± 5.38° (P > 0.05), preoperational and postoperational, respectively.

Conclusions: None of these 3 techniques cause or aggravate nasal obstruction, and all of them can achieve high cosmetic satisfaction. Technique 1 and technique 2 are suitable for the patients with moderate and moderate to severe short nose that is common in East Asia, which can better increase the protrusion of the tip and length of the nose. Technique 3 is suitable for the patients with better shape of the nose, who need to slightly increase the protrusion of the nasal tip and increase the upward rotation.
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http://dx.doi.org/10.1097/SAP.0000000000002638DOI Listing
March 2021

Neuroinvasion of SARS-CoV-2 in human and mouse brain.

J Exp Med 2021 03;218(3)

Sorbonne Université, INSERM U1127, French National Centre for Scientific Research, Joint Research Unit 7225, Paris Brain Institute, Institut du Cerveau et de la Moelle Épinière, Paris, France.

Although COVID-19 is considered to be primarily a respiratory disease, SARS-CoV-2 affects multiple organ systems including the central nervous system (CNS). Yet, there is no consensus on the consequences of CNS infections. Here, we used three independent approaches to probe the capacity of SARS-CoV-2 to infect the brain. First, using human brain organoids, we observed clear evidence of infection with accompanying metabolic changes in infected and neighboring neurons. However, no evidence for type I interferon responses was detected. We demonstrate that neuronal infection can be prevented by blocking ACE2 with antibodies or by administering cerebrospinal fluid from a COVID-19 patient. Second, using mice overexpressing human ACE2, we demonstrate SARS-CoV-2 neuroinvasion in vivo. Finally, in autopsies from patients who died of COVID-19, we detect SARS-CoV-2 in cortical neurons and note pathological features associated with infection with minimal immune cell infiltrates. These results provide evidence for the neuroinvasive capacity of SARS-CoV-2 and an unexpected consequence of direct infection of neurons by SARS-CoV-2.
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http://dx.doi.org/10.1084/jem.20202135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808299PMC
March 2021

A Semi-Supervised Deep Rule-Based Approach for Complex Satellite Sensor Image Analysis.

IEEE Trans Pattern Anal Mach Intell 2021 Feb 4;PP. Epub 2021 Feb 4.

Large-scale {(large-area)}, fine spatial resolution satellite sensor images are valuable data sources for Earth observation while not yet fully exploited by research communities for practical applications. Often, such images exhibit highly complex geometrical structures and spatial patterns, and distinctive characteristics of multiple land-use categories may appear at the same region. Autonomous information extraction from these images is essential in the field of pattern recognition within remote sensing, but this task is extremely challenging due to the spectral and spatial complexity captured in satellite sensor imagery. In this research, a semi-supervised deep rule-based approach for satellite sensor image analysis (SeRBIA) is proposed, where large-scale satellite sensor images are analysed autonomously and classified into detailed land-use categories. Using an ensemble feature descriptor derived from pre-trained AlexNet and VGG-VD-16 models, SeRBIA is capable of learning continuously from both labelled and unlabelled images through self-adaptation without human involvement or intervention. Extensive numerical experiments were conducted on both benchmark datasets and real-world satellite sensor images to comprehensively test the validity and effectiveness of the proposed method. The novel information mining technique developed here can be applied to analyse large-scale satellite sensor images with high accuracy and interpretability, across a wide range of real-world applications.
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http://dx.doi.org/10.1109/TPAMI.2020.3048268DOI Listing
February 2021

N-terminal pro-brain natriuretic peptide and sudden cardiac death in hypertrophic cardiomyopathy.

Heart 2020 Dec 24. Epub 2020 Dec 24.

State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

Objective: Elevated levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) are associated with heart failure-related death in hypertrophic cardiomyopathy (HCM), but the relationship between NT-proBNP level and sudden cardiac death (SCD) in HCM remains undefined.

Methods: The study prospectively enrolled 977 unrelated patients with HCM with available NT-proBNP results who were prospectively enrolled and followed for 3.0±2.1 years. The Harrell's C-statistic under the receiver operating characteristic curve was calculated to evaluate discrimination performance. A combination model was constructed by adding NT-proBNP tertiles to the HCM Risk-SCD model. The correlation between log NT-proBNP level and cardiac fibrosis as measured by late gadolinium enhancement (LGE) or Masson's staining was analysed.

Results: During follow-up, 29 patients had SCD. Increased log NT-proBNP levels were associated with an increased risk of SCD events (adjusted HR 22.27, 95% CI 10.93 to 65.63, p<0.001). The C-statistic of NT-proBNP in predicting SCD events was 0.80 (p<0.001). The combined model significantly improved the predictive efficiency of the HCM Risk-SCD model from 0.72 to 0.81 (p<0.05), with a relative integrated discrimination improvement of 0.002 (p<0.001) and net reclassification improvement of 0.67 (p<0.001). Furthermore, log NT-proBNP levels were significantly correlated with cardiac fibrosis as detected either by LGE (r=0.257, p<0.001) or by Masson's trichrome staining in the myocardium (r=0.198, p<0.05).

Conclusion: NT-proBNP is an independent predictor of SCD in patients with HCM and may help with risk stratification of this disease.
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http://dx.doi.org/10.1136/heartjnl-2020-317701DOI Listing
December 2020

Effect of aspartic acid on the crystallization kinetics of ACP and dentin remineralization.

J Mech Behav Biomed Mater 2021 03 5;115:104226. Epub 2020 Dec 5.

Department of Stomatology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, PR China. Electronic address:

Type I collagen and non-collagen proteins are the main organic components of dentin. This study aimed to investigate the biomimetic remineralization of demineralized dentin by aspartic acid (Asp), which is abundant in non-collagenous proteins (NCPs). Asp was added to a mineralizing solution containing polyacrylic acid (PAA) to explore the mechanism of Asp regulating the pure amorphous calcium phosphate (ACP) phase transition process. The remineralization process and superstructure of the remineralized layer of demineralized dentin were evaluated and analyzed by transmission electron microscope (TEM) and scanning electron microscope (SEM), and the biological stability of the remineralized layer was investigated by collagenase degradation experiment. It demonstrated that Asp promoted the crystallization kinetics of PAA-stabilized amorphous calcium phosphate to hydroxyapatite (HAP), and shortened the remineralization time of demineralized dentin from 7 days to 2 days. The newly formed remineralized dentin had similar morphology and biological stability to the natural dentin layer. The presence of a large number of Asp residues in NCPs promoted the phase transformation of ACP, and further revealed the mechanism of action of NCPs in dentin biomineralization. This experiment also showed that Asp promoted the biomimetic remineralization of dentin; the morphology and hierarchical structure of remineralized layer was similar to that of natural teeth, and had good biological properties.
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http://dx.doi.org/10.1016/j.jmbbm.2020.104226DOI Listing
March 2021

Long-Term Prognosis of Moderate to Severe Coronary Artery Calcification in Patients Undergoing Percutaneous Coronary Intervention.

Circ J 2020 12 9;85(1):50-58. Epub 2020 Dec 9.

Department of Cardiology, Fu Wai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences.

Background: Moderate/severe coronary artery calcification (CAC) predicts worse clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). However, to date most studies have been modest in size and with limited follow-up. We aimed to assess the association between calcification severity and long-term clinical outcomes in a large cohort undergoing PCI.Methods and Results:In total, 10,068 consecutive patients who underwent PCI at Fuwai Hospital were enrolled in this prospective observational study. Patients were categorized as none/mild or moderate/severe CAC according to the severity of the target lesion by visual assessment of coronary angiography. Major adverse cardiovascular events (MACE), a composite event of death, myocardial infarction and revascularization, at 5 years were assessed. None/mild CAC was observed in 8,229 (81.7%) patients, and moderate/severe CAC was observed in 1,839 (18.3%) patients. Patients with moderate/severe CAC had a significantly higher rate of 5-year unplanned revascularization (15.2% vs. 13.2%, P=0.022) and MACE (20.7% vs. 17.9%, P=0.005). After propensity score matching, the moderate/severe CAC group still had a higher rate of 5-year unplanned revascularization (15.2% vs. 12.6%, P=0.019). Cox regression analysis using clinically significant variables revealed moderate/severe calcification was independently associated with higher risk of 2-year unplanned target vessel revascularization (hazard ratio (HR)=1.287, 95% confidence interval (CI): 1.036-1.600, P=0.023) and MACE (HR=1.242, 95% CI: 1.039-1.484, P=0.017), but not 5-year unplanned revascularization and MACE.

Conclusions: In patients undergoing PCI, moderate/severe coronary calcification increases the risk of long-term MACE.
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http://dx.doi.org/10.1253/circj.CJ-20-0761DOI Listing
December 2020

Predictive value of free triiodothyronine (FT3) to free thyroxine (FT4) ratio in long-term outcomes of euthyroid patients with three-vessel coronary artery disease.

Nutr Metab Cardiovasc Dis 2021 02 17;31(2):579-586. Epub 2020 Oct 17.

Fu Wai Hospital, National Center for Cardiovascular Diseases, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, China. Electronic address:

Background And Aims: Whether routine assessment of FT3/FT4 ratio in euthyroid patients with three-vessel disease (3VD) could help identify high-risk individuals remains unclear. This study evaluated the relationship between FT3/FT4 ratio and long-term clinical outcomes in this specific population.

Methods And Results: This study included 2106 euthyroid patients with 3VD (stenoses of ≥50% in right coronary artery, left circumflex and left anterior descending). Patients were categorized into three groups according to tertiles of FT3/FT4 ratio (Q1>2.58,n = 704; 2.2 ≤ Q2<2.58, n = 706; Q3<2.22, n = 696). The median follow-up time was 5.3 years, during which 206 deaths and 332 MACCEs (consisting of all-cause death, myocardial infarction, and stroke) occurred. Compared with the other two groups, patients with low level of FT3/FT4 ratio tended to be female, older, diabetic, and had significantly higher incidences of all-cause death, cardiac death and MACCE (all P < 0.05). Cox regression analysis showed that patients with low level of FT3/FT4 ratio had higher risks of long-term cardiac death (adjusted HR = 1.87, 95% CI 1.06-3.28, P = 0.030) and MACCE (adjusted HR = 1.43, 95% CI 1.07-1.93, P = 0.017) than those with high level of FT3/FT4 ratio. Subgroup analysis showed there was a significant interaction between FT3/FT4 ratio and age (≥65 years vs.<65 years) for MACCE (P = 0.029).

Conclusion: Low level of FT3/FT4 ratio is independently associated with an increased risk of long-term cardiac death and MACCE in euthyroid patients with 3VD. Routine assessment of FT3/FT4 ratio might be helpful to identify high-risk individuals in this specific population.
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http://dx.doi.org/10.1016/j.numecd.2020.10.011DOI Listing
February 2021

Body mass index and mortality in patients with severe coronary artery diseases: A cohort study from China.

Nutr Metab Cardiovasc Dis 2021 02 17;31(2):448-454. Epub 2020 Sep 17.

Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China; State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China; National Clinical Research Center for Cardiovascular Diseases, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, People's Republic of China. Electronic address:

Background And Aims: It is still controversial whether obesity and overweight increase the risk of mortality for patients with coronary artery disease. The current study aimed to investigate the relationship between body mass index (BMI) and mortality in patients with triple-vessel disease (TVD).

Methods And Results: From April 2004 to February 2011, 8943 patients with angiographically confirmed TVD were consecutively enrolled. Patients were divided into five groups according to BMI: underweight (<18.5 kg/m), normal weight (18.5-23.9 kg/m), overweight: (24-27.9 kg/m), mild obesity (28-31.9 kg/m), and severe obesity (≥32 kg/m). The primary end point was all-cause death. Subgroup analysis was performed for treatment strategies: revascularization and medical treatment alone. During a median follow-up of 7.5 years, lower risks of mortality were observed in patients with overweight (adjusted HR 0.85, 95% CI 0.75-0.97) and mild obesity (adjusted HR 0.83, 95% CI 0.69-1.00) compared to those with normal weight. Polynomial Cox regression suggested a U-shape association between BMI and adjusted mortality risk. In the revascularization subgroup, there was a significantly higher mortality risk in patients with severe obesity (adjusted HR 1.57, 95% CI 1.03-2.40) than in those with normal weight. While in the medical treatment subgroup, mortality risk decreased as BMI increased, with the lowest risk being observed in patients with severe obesity.

Conclusion: There is a U-shape relationship between BMI and all-cause death in patients with TVD, with increased risks among both underweight and severely obese patients. This relationship may be influenced by treatment strategies.
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http://dx.doi.org/10.1016/j.numecd.2020.09.011DOI Listing
February 2021

Comparison of intravitreal injection of conbercept and triamcinolone acetonide for macular edema secondary to branch retinal vein occlusion.

Int J Ophthalmol 2020 18;13(11):1765-1772. Epub 2020 Nov 18.

Department of Ophthalmology, the Second Hospital of Dalian Medical University, Dalian 116027, Liaoning Province, China.

Aim: To compare the safety and efficacy of the intravitreal injection of conbercept (IVC) and triamcinolone acetonide (IVTA) for macular edema (ME) secondary to branch retinal vein occlusion (BRVO).

Methods: A prospective, randomized clinical study. Patients with ME secondary to BRVO were randomly assigned to either IVC group or IVTA group at a ratio of 2:1 and a 12-month follow-up was performed. The efficacy outcome measures included the mean changes and differences in best corrected visual acuity (BCVA) and the central retinal thickness (CRT). The safety profiles and the mean retreatment intervals were also compared.

Results: There was no statistically significant difference of baseline between the two groups (IVC group, =36; IVTA group, =17). At 12mo, the BCVA letters improved by 27.31±18.36 in the IVC group, and 13.53±11.37 in the IVTA group (=0.0004). CRT reduction was 253.33±163.69 and 150.24±134.32 µm, respectively (=0.0034). The mean BCVA in the IVC group was superior to that of the IVTA group for months 6-12 (<0.01). The mean CRT at 9 and 12mo were thinner in the IVC group compared to the IVTA group (<0.01). The mean retreatment interval in the IVC group was longer than that in the IVTA group (97.40±36.27d 68.71±36.38d, =0.0030). One eye in the IVC group and seven eyes in the IVTA group developed elevated intraocular pressure (IOP; =0.0012). The proportion of eyes with cataract new-onset or progression were 19.44% in the IVC group and 64.71% in the IVTA group (=0.0012).

Conclusion: IVC could maintain or improve BCVA and reduce CRT for a longer time and have longer retreatment interval than IVTA. In addition, patients treated with IVTA are more susceptible to IOP elevation and cataract progression.
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http://dx.doi.org/10.18240/ijo.2020.11.13DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7590870PMC
November 2020

A conserved LDL-receptor motif regulates corin and CD320 membrane targeting in polarized renal epithelial cells.

Elife 2020 11 2;9. Epub 2020 Nov 2.

Cyrus Tang Hematology Center, Collaborative Innovation Center of Hematology, State Key Laboratory of Radiation Medicine and Prevention, Soochow University, Suzhou, China.

Selective protein distribution on distinct plasma membranes is important for epithelial cell function. To date, how proteins are directed to specific epithelial cell surface is not fully understood. Here we report a conserved DSSDE motif in LDL-receptor (LDLR) modules of corin (a transmembrane serine protease) and CD320 (a receptor for vitamin B12 uptake), which regulates apical membrane targeting in renal epithelial cells. Altering this motif prevents specific apical corin and CD320 expression in polarized Madin-Darby canine kidney (MDCK) cells. Mechanistic studies indicate that this DSSDE motif participates in a Rab11a-dependent mechanism that specifies apical sorting. In MDCK cells, inhibition of Rab11a, but not Rab11b, expression leads to corin and CD320 expression on both apical and basolateral membranes. Together, our results reveal a novel molecular recognition mechanism that regulates LDLR module-containing proteins in their specific apical expression in polarized renal epithelial cells.
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http://dx.doi.org/10.7554/eLife.56059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7605860PMC
November 2020

Distinct Transcriptomic Reprogramming in the Wheat Stripe Rust Fungus During the Initial Infection of Wheat and Barberry.

Mol Plant Microbe Interact 2021 Feb 11;34(2):198-209. Epub 2021 Jan 11.

College of Plant Protection, Northwest A&F University, Yangling, Shaanxi, People's Republic of China.

f. sp. is the causal agent of wheat stripe rust that causes severe yield losses all over the world. As a macrocyclic heteroecious rust fungus, it is able to infect two unrelated host plants, wheat and barberry. Its urediniospores infect wheat and cause disease epidemic, while its basidiospores parasitize barberry to fulfill the sexual reproduction. This complex life cycle poses interesting questions on the different mechanisms of pathogenesis underlying the infection of the two different hosts. In the present study, transcriptomes of f. sp. during the initial infection of wheat and barberry leaves were qualitatively and quantitatively compared. As a result, 142 wheat-specifically expressed genes (WEGs) were identified, which was far less than the 2,677 barberry-specifically expressed genes (BEGs). A larger proportion of evolutionarily conserved genes were observed in BEGs than that in WEGs, implying a longer history of the interaction between f. sp. and barberry. Additionally, f. sp. differentially expressed genes (DEGs) between wheat at 1 and 2 days postinoculation (dpi) and barberry at 3 and 4 dpi were identified by quantitative analysis. Gene Ontology analysis of these DEGs and expression patterns of f. sp. pathogenic genes, including those encoding candidate secreted effectors, cell wall-degrading enzymes, and nutrient transporters, demonstrated that urediniospores and basidiospores exploited distinct strategies to overcome host defense systems. These results represent the first analysis of the f. sp. transcriptome in barberry and contribute to a better understanding of the evolutionary processes and strategies of different types of rust spores during the infection process on different hosts.[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.
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http://dx.doi.org/10.1094/MPMI-08-20-0244-RDOI Listing
February 2021

Proinflammatory S100A9 Regulates Differentiation and Aggregation of Neural Stem Cells.

ACS Chem Neurosci 2020 11 20;11(21):3549-3556. Epub 2020 Oct 20.

Laboratory of Stem Cell and Tissue Engineering, Chongqing Medical University & Institute of Photonics and Photon-Technology, Northwest University, 1 Xue Fu Avenue, Xi'an, Shaanxi 710127, China.

Inflammation is the primary pathological feature of neurodegenerative diseases such as Alzheimer's disease (AD) and Parkinson's disease. Proinflammatory molecules (e.g., S100A9) play important roles during the progression of the diseases by regulating behavior and fate of multiple cell types in the nervous system. Our earlier studies reveal that S100A9 is toxic to neurons, and its interaction with Aβ peptides leads to the formation of large nontoxic amyloidogenic aggregates, suggesting a protective role of coaggregation with Aβ amyloids. We herein demonstrate that S100A9 interacts with neural stem cells (NSCs) and causes NSC differentiation. In the brain of transgenic AD mouse models, we found large quantities of proinflammatory S100A9, which colocalizes with the differentiated NSCs. NSC sphere formation, which is a representative character of NSC stemness, is also substantially inhibited by S100A9. These results suggest that S100A9 is a representative marker for the inflammatory conditions in AD, and it promotes NSC differentiation. Intriguingly, in contrast to the death of both stem and differentiated NSCs caused by high S100A9 doses, S100A9 at a moderate concentration is toxic only to the early differentiated NSCs but not the stem cells. We therefore postulate that, at the early stage of AD, the expression of S100A9 leads to NSC differentiation, which remedies the neuron damage. The application of drugs, which help maintain NSC stemness (e.g., the platelet-derived growth factor, PDGF), may help overcome the acute inflammatory conditions and improve the efficacy of NSC transplantation therapy.
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http://dx.doi.org/10.1021/acschemneuro.0c00365DOI Listing
November 2020

Gefitinib-Induced Cutaneous Toxicities in Brown Norway Rats Are Associated with Macrophage Infiltration.

Inflammation 2020 Dec;43(6):2137-2146

Beijing University of Chinese Medicine, Beijing, 100029, China.

Gefitinib (Iressa), is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), used in the targeted treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC). Skin toxicity is the major adverse effect observed in patients treated with EGFR-targeted TKIs such as gefitinib and erlotinib. To date, a corresponding skin animal model has not been established to address the mechanisms of these effects. Therefore, we analyzed the skin rash phenotype and its pathological features in Brown Norway (BN) rats treated with gefitinib 2.5 mg, 5.0 mg, or 10 mg/100 g/day for 4 weeks. We found that treatment with gefitinib led to weight loss, rash, itching, and hair loss in a dose-dependent manner. We also investigated the skin pathology and found that the animal model showed thickening of the epidermis, loss of moisture, and apoptosis of keratinocytes. Immunohistochemistry, flow cytometry, and analysis of monocytes and leukocytes in the blood revealed increased macrophage infiltration was associated with the cutaneous toxicities induced by gefitinib in the BN rats. Finally, we found that gefitinib-induced cutaneous toxicity is significantly associated with three inflammatory cytokines known to be secreted by activated macrophages, TREM-1, CINC-2, and CINC-3.
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http://dx.doi.org/10.1007/s10753-020-01281-2DOI Listing
December 2020

A Computationally Efficient Multiclass Time-Frequency Common Spatial Pattern Analysis on EEG Motor Imagery.

Annu Int Conf IEEE Eng Med Biol Soc 2020 07;2020:514-518

Common spatial pattern (CSP) is a popular feature extraction method for electroencephalogram (EEG) motor imagery (MI). This study modifies the conventional CSP algorithm to improve the multi-class MI classification accuracy and ensure the computation process is efficient. The EEG MI data is gathered from the Brain-Computer Interface (BCI) Competition IV. At first, a bandpass filter and a timefrequency analysis are performed for each experiment trial. Then, the optimal EEG signals for every experiment trials are selected based on the signal energy for CSP feature extraction. In the end, the extracted features are classified by three classifiers, linear discriminant analysis (LDA), naïve Bayes (NVB), and support vector machine (SVM), in parallel for classification accuracy comparison.The experiment results show the proposed algorithm average computation time is 37.22% less than the FBCSP (1 winner in the BCI Competition IV) and 4.98% longer than the conventional CSP method. For the classification rate, the proposed algorithm kappa value achieved 2nd highest compared with the top 3 winners in BCI Competition IV.
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http://dx.doi.org/10.1109/EMBC44109.2020.9176705DOI Listing
July 2020