Publications by authors named "Li Lu"

2,212 Publications

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MIT1, encoding a 15-cis-ζ-carotene isomerase, regulates tiller number and stature in rice.

J Genet Genomics 2021 Jan 30. Epub 2021 Jan 30.

National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing, 100081, China. Electronic address:

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http://dx.doi.org/10.1016/j.jgg.2020.11.008DOI Listing
January 2021

Fluorine-induced surface metallization for ammonia synthesis under photoexcitation up to 1550 nm.

Angew Chem Int Ed Engl 2021 Mar 2. Epub 2021 Mar 2.

McGill University, Physics, CANADA.

The regulation of electronic states at the semiconductor surface/interface is of great importance in catalysis, microelectronics, and energy conversion. Herein, we report that the first observation of surface metallization of TiO 2-x induced by fluoride ions. The emerging metallic states are contributed by the 3d orbital of surface Ti and the 2p orbital of surface bridging F, which are intrinsically originated from the strong electron repulsion between F - and adjacent Ti 3+ . The metalized TiO 2-x with reduced work function and downward band bending possesses high electron-donating power to supported Ru species via atomic-scale ohmic contacts, exhibiting unprecedented photocatalytic performances for ammonia synthesis across the entire solar spectrum region (200-1550 nm) at room temperature. Mechanism and kinetic analysis revealed that the loaded Ru could behave as efficient electron sinks to accumulate photogenerated electrons and that the metallic surface markedly enhanced the dissociation of H 2 and N 2 by the hot electrons generated by the visible or even infrared light irradiation.
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http://dx.doi.org/10.1002/anie.202100572DOI Listing
March 2021

Apocynin prevents reduced myocardial nerve growth factor, contributing to amelioration of myocardial apoptosis and failure.

Clin Exp Pharmacol Physiol 2021 Mar 1. Epub 2021 Mar 1.

Schepens Eye Research Institute, Massachusetts Eye and Ear, Harvard Medical School Affiliate, Boston, MA, USA.

Reduced nerve growth factor (NGF) is associated with cardiac sympathetic nerve denervation in heart failure (HF) which is characterized by increased oxidative stress. Apocynin is considered an antioxidant agent which inhibits NADPH oxidase activity and improves reactive oxygen species scavenging. However, it is unclear whether apocynin prevents reduced myocardial NGF, leading to improvement of cardiac function in HF. In this study, we tested the hypothesis that apocynin prevents reduced myocardial NGF, contributing to amelioration of myocardial apoptosis and failure. Rabbits with myocardial infarction (MI) or sham operation were randomly assigned to receive apocynin or placebo for 4 weeks. MI rabbits exhibited left ventricular (LV) dysfunction, and elevation in oxidative stress, as evidenced by a decreased reduced-to-oxidized glutathione ratio and an increased 4-hydroxynonenal expression, and reduction in NGF and NGF receptor tyrosine kinase A (TrKA) expression in the remote non-infarcted myocardium. Apocynin treatment ameliorated LV dysfunction, reduced oxidative stress, prevented decreases in NGF and TrKA expression and reduced cardiomyocyte apoptosis after MI. In cultured H9C2 cardiomyocytes, hypoxia or hydrogen peroxide decreased NGF expression, and apocynin normalized hypoxia-induced reduction of NGF. Recombinant NGF attenuated hypoxia-induced apoptosis. Apocynin prevented hypoxia-induced apoptosis, and the suppressive effect of apocynin on apoptosis was abolished by NGF receptor TrKA inhibitor K252a. We concluded that apocynin prevented reduced myocardial NGF, leading to attenuation of cardiomyocyte apoptosis and LV remodelling and dysfunction in HF after MI. These findings suggest that strategies to prevent NGF reduction by inhibition of oxidative stress may be of value in amelioration of LV dysfunction in HF.
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http://dx.doi.org/10.1111/1440-1681.13465DOI Listing
March 2021

Assessment of multiple pathways involved in the inhibitory effect of HCG22 on oral squamous cell carcinoma progression.

Mol Cell Biochem 2021 Mar 1. Epub 2021 Mar 1.

Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, China Medical University, 117 Nanjing Street, Shenyang, 110002, China.

LncRNAs have been proposed to be associated with the tumorigenesis and progression of oral squamous cell carcinoma (OSCC). LncRNA HLA complex group 22 (HCG22) was reported to be lowly expressed and associated with poor prognosis in head and neck squamous cell carcinoma (HNSCC). However, the biological role and related mechanism of HCG22 in OSCC have not been characterized. HCG22 expression in OSCC cells was detected by qRT-PCR. Cell proliferation, invasion, and apoptosis were evaluated by Bromodeoxyuridine (BrdU) proliferation assay, Transwell invasion assay, and flow cytometry analysis, respectively. The protein levels of proliferating cell nuclear antigen (PCNA), E-cadherin, Vimentin, Bcl-2, Bax, protein kinase B (Akt), phosphorylated Akt (p-Akt), mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), and β-catenin were detected by western blot. Cell growth evaluation was performed using in vitro colony formation assay and in vivo tumor xenograft assay. We found that HCG22 was weakly expressed in OSCC cells. HCG22 overexpression inhibited cell proliferation and invasion and induced apoptosis in OSCC cells. The levels of PCNA, Vimentin, and Bcl-2 were decreased and E-cadherin and Bax expression was elevated in OSCC cells after HCG22 overexpression. Additionally, HCG22 overexpression inhibited the Akt, mTOR and Wnt/β-catenin pathways. Activation of Akt, mTOR, and Wnt/β-catenin pathways attenuated the anti-tumor property of HCG22 in OSCC cells. Furthermore, HCG22 overexpression inhibited the growth of OSCC cells in vitro and in vivo. In conclusion, HCG22 exerted anti-tumor property in OSCC by inhibiting the Akt, mTOR, and Wnt/β-catenin pathways.
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http://dx.doi.org/10.1007/s11010-021-04091-8DOI Listing
March 2021

Determination of Fentanyl, Alpha-Methylfentanyl, Beta-Hydroxyfentanyl, and the Metabolite Norfentanyl in Rat Urine by LC-MS/MS.

J Anal Toxicol 2021 Feb 27. Epub 2021 Feb 27.

Shanghai Key Laboratory of Crime Scene Evidence, Shanghai 200437, China.

Fentanyl and its analogs are potent synthetic opioids with a high potential for abuse and dependence. They have become major contributors to opioid deaths. This study aimed to determine whether the metabolites of fentanyl, alpha-methylfentanyl and beta-hydroxyfentanyl, excreted in the urine, can demonstrate historical drug exposure. Fentanyl is primarily metabolized via CYP3A4 into norfentanyl, although there is little research on its metabolism into alpha-methylfentanyl and beta-hydroxyfentanyl. We conducted in vitro experiments with human liver microsomes (HLM) and rat liver microsomes (RLM) to elucidate the major metabolic pathways of alpha-methylfentanyl and beta-hydroxyfentanyl using UHPLC coupled with mass spectrometry. The results showed that both alpha-methylfentanyl and beta-hydroxyfentanyl were predominantly metabolized into norfentanyl in HLM and RLM. Urine samples were collected at different intervals from 0 h to 72 h after intravenous administration of alpha-methylfentanyl and beta-hydroxyfentanyl (20 μg/kg) to Sprague-Dawley rats. We prepared the samples by liquid-liquid extraction, and the internal standard (IS) was cariprazine. A sensitive, rapid LC-MS/MS method was developed and validated to determine four analytes in the urine. The lower limit of qualification (LLOQ) in urine was 2 pg/ml for fentanyl, 5 pg/ml for alpha-methylfentanyl, 10 pg/ml for beta-hydroxyfentanyl, and 40 pg/ml for norfentanyl. The analytical range was 0.002-2 ng/ml for fentanyl, 0.005-5 ng/ml for alpha-methylfentanyl, 0.01-10 ng/ml for beta-hydroxyfentany and 0.04-40 ng/ml for norfentanyl. All analytes demonstrated good linearity (R2 > 0.99). The extraction recoveries were in the 67.8%-92.1% range, and the IS-normalized matrix effects were between 55.5%-74.0% (CV < 15%). Our data indicated that norfentanyl has a higher concentration in rat urine and was detectable for at least three days after exposure to these compounds. This developed method may be useful in various fields, including forensic analysis, workplace drug testing, and monitoring drug abuse.
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http://dx.doi.org/10.1093/jat/bkab021DOI Listing
February 2021

Sleep disturbance and its association with quality of life among psychiatric nurses in China.

PeerJ 2021 17;9:e10659. Epub 2021 Feb 17.

Center for Cognition and Brain Sciences, University of Macau, Macau SAR, China.

Background: Sleep disturbance is associated with a number of negative adverse outcomes. This study examined the prevalence of sleep disturbance and its association with demographic and clinical characteristics and quality of life (QOL) in psychiatric nurses in China.

Methods: This is a multi-center, cross-sectional study involving 11 psychiatric hospitals in China. Three types of sleep disturbance (difficulty initiating sleep (DIS), difficulty maintaining sleep (DMS) and early-morning awakening (EMA)) and QOL were measured by standardized questions or instruments.

Results: A total of 1,847 psychiatric nurses participated. The overall prevalence of at least one type of sleep disturbance was 71.5% (95% CI [69.3-73.5]); the prevalence of DIS, DMS and EMA was 58.5% (95% CI [56.2-60.8]), 53.7% (95% CI [51.4-56.0]) and 54.6% (95% CI [52.3-56.9]), respectively. Nurses with sleep disturbance had significantly lower QOL in physical ( = 219.12, < 0.001), psychological ( = 72.18, < 0.001), social ( = 37.57, < 0.001) and environmental domains ( = 95.45, < 0.001). Multivariable logistic regression analyses revealed that shift work (DIS, OR = 1.6, 95% CI [1.28-1.98]; DMS, OR = 1.2, 95% CI [1.001-1.54]; EMA, OR = 1.3, 95% CI [1.02-1.58]) and alcohol use (DIS, OR = 1.8, 95% CI [1.46-2.32]; DMS, OR = 1.8, 95% CI [1.43-2.23]; EMA, OR = 1.7, 95% CI [1.33-2.07]) were positively associated with sleep disturbance, while higher monthly income (DIS, OR = 0.5, 95% CI [0.38-0.75]; DMS, OR = 0.7, 95% CI [0.51-0.98]) was negatively associated with sleep disturbance.

Conclusion: Sleep disturbance was common among nurses in psychiatric hospitals in China, particularly those on shifts and having alcohol use. Health authorities should develop effective measures to reduce risk of sleep disturbance in this population.
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http://dx.doi.org/10.7717/peerj.10659DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896499PMC
February 2021

Seroepidemiology of pertussis in China: A population-based, cross-sectional study.

Vaccine 2021 Feb 25. Epub 2021 Feb 25.

Department of Immunization and Prevention, Beijing Center for Disease Prevention and Control, Beijing Research Center for Preventive Medicine, Beijing 100013, China. Electronic address:

Background: Despite high pertussis vaccination coverage and significant decrease of pertussis since the adoption of the Expanded Programme on Immunization (1978), increased pertussis incidence has been reported in China from 2013 to 2017. This study aimed at evaluating the immune response to pertussis among vaccinated children and beyond in China.

Methods: The study recruited 2 144 healthy subjects. Serum IgG antibodies against pertussis toxin (anti-PT IgG) were measured by ELISA. Anti-PT IgG concentration (GMC), seropositivity rate (GMC ≥ 40 IU/ml), and recent infection rate (GMC > 100 IU/ml) were calculated. Participants ≤ 2 years-old were further stratified by vaccination schedule intervals and participants ≤ 6 years-old by vaccine used (Domestic DTaP or DTaP-IPV//PRP ~ T (Pentaxim, SP)).

Results: Among 0-6-year-olds, the anti-PT IgG GMC was 5.99 IU/ml (95%CI 5.39-6.67). The GMC increased in accordance with the primary vaccination series (4-6 months) and the toddler booster (18-23 months), and continuously declined thereafter to its nadir at 6 years-old [3.72 IU/ml (95%CI 2.91-4.77)]. GMCs were markedly higher in those vaccinated with DTaP-IPV/PRP ~ T compared to DTaP. In individuals > 6 years-old, the GMC was 5.67 IU/ml (95%CI 5.36-6.00), the seropositivity rate was 6.7% (95%CI 5.5-7.9) and the recent infection rate was 1.2% (95%CI 0.7-1.7). The seropositivity rates increased from 6 years-old and peaked at 9 years-old (10.3% [95%CI 0.7-19.8]).

Conclusions: Vaccination against pertussis increases anti-PT IgG, but wanes over time. The sero-estimated infection rates increase from school age and peak at about 9 years-old. These results support the addition of a booster of pertussis vaccine at preschool age.
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http://dx.doi.org/10.1016/j.vaccine.2021.02.032DOI Listing
February 2021

cDNA cloning of a novel lectin that induce cell apoptosis from Artocarpus hypargyreus.

Chin J Nat Med 2021 Feb;19(2):81-89

Department of Biochemistry and Molecular Biology, Guangxi Medical University, Nanning 530021, China. Electronic address:

We isolated a novel lectin (AHL) from Artocarpus hypargyreusHance and showed its immunomodulatory activities. In this study, the amino acid sequence of AHL was determined by cDNA sequencing. AHL cDNA (875bp) contains a 456-bp open reading frame (ORF), which encodes a protein with 151 amino acids. AHL is a new member of jacalin-related lectin family (JRLs), which share high sequence similarities to KM+ and Morniga M, and contain the conserved carbohydrate binding domains. The antitumor activity of AHL was also explored using Jurkat T cell lines. AHL exhibits a strong binding affinity to cell membrane, which can be effectively inhibited by methyl-α-D-galactose. AHL inhibits cell proliferation in a time- and dose-dependent manner through apoptosis, evidenced by morphological changes, phosphatidylserine externalization, poly ADP-ribose polymerase (PARP) cleavage, Bad and Bax up-regulation, and caspase-3 activation. We further showed that the activation of ERK and p38 signaling pathways is involved for the pro-apoptotic effect of AHL.
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http://dx.doi.org/10.1016/S1875-5364(21)60009-2DOI Listing
February 2021

Neutrophil Extracellular Traps Promote Aberrant Macrophages Activation in Behçet's Disease.

Front Immunol 2020 5;11:590622. Epub 2021 Feb 5.

Department of Rheumatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, The Ministry of Education Key Laboratory, National Clinical Research Center for Dermatologic and Immunologic Diseases, Beijing, China.

Neutrophil extracellular traps (NETs) are upregulated and promote thrombosis in Behçet's disease (BD). However, whether NETs promote autoinflammation in BD remains unclear. This study aimed to investigate the potential role of NETs in promoting macrophage activation in BD. Firstly, we quantified NETs by measuring double-stranded DNA (dsDNA) using PicoGreen and calculating the proportion of NETosis. Then macrophages were stimulated with BD- or healthy controls (HC)-derived NETs, and IL-8 and TNF-α production and IFN-γ CD4 T cells differentiation were measured using ELISA and flow cytometry, respectively. The protein components in NETs were analyzed by western blot. Macrophages were stimulated with Histone H4 neutralized NETs, and IL-8 and TNF-α production were measured using ELISA. The level of 8-hydroxydeoxyguanosine (8-OHdG) DNA in NETs was measured using ELISA. The levels of reactive oxygen species (ROS) in serum and neutrophils were measured using ROS probes by a microplate reader and flow cytometry. We found that circulating NETs and neutrophil-derived NETs were significantly higher in BD than HC. BD NETs stimulated macrophages produced higher levels of IL-8 and TNF-α, and promoted IFN-γ CD4 T cells differentiation. BD NETs were enriched in Histone H4, and neutralizing Histone H4 abrogated the BD NETs-mediated IL-8 production by macrophages, but not TNF-α. Also, BD neutrophils produced more 8-OHdG DNA than HC neutrophils, and the percentage of 8-OHdG DNA in dsDNA from BD neutrophils was also higher than that of HC neutrophils. The ROS levels in serum and neutrophils were both higher in BD than HC. Our findings suggested that excessive BD NETs promoted macrophages activation and facilitated IFN-γ CD4 T cells differentiation. Higher levels of Histone H4 and oxidized DNA in BD NETs might mediate macrophages hyperactivation.
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http://dx.doi.org/10.3389/fimmu.2020.590622DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901995PMC
February 2021

Short-chain fatty acids resource recovery potential from algal sludge via anaerobic fermentation under various pH values.

Chemosphere 2021 Feb 15;275:129954. Epub 2021 Feb 15.

State Key Laboratory of Environmental Criteria and Risk Assessment, Chinese Research Academy of Environmental Sciences, Beijing, 100012, PR China.

The harvesting of algal sludge from eutrophic lakes, including the large quantity of organic matters, has the potential to be used as valuable products through the process of resource recovery. This study investigates the fatty acid production potential from algal sludge via anaerobic fermentation under different pH values. The results indicated that the recovery of short-chain fatty acids (SCFAs) was the highest (3269.25 ± 32.89 mg·COD/L) at pH 11 after 7 days of fermentation. The SCFAs concentration at pH value 11 was 6.24, 1.27, 4.90, and 0.53 times higher compared with that at pH value 3, 5, 7, and 9, respectively. The SCFAs production was continually increased from day 1 to day 7 at pH value 7, 9, and 11. Much fewer middle- and long-chain fatty acids were produced compared with SCFAs. Gross. fatty acid production was the highest at pH 11. The concentrations of soluble protein and polysaccharide were the highest at pH 11, implying that the disruption of algal cells could have a high value at pH 11. The polysaccharide concentration was the lowest at pH 7. The fluorescence excitation-emission matrix profile implied that the disruption of algal cells was the greatest at pH 11. Methane production was greatest at pH 7 and 9. Overall, the results of this study revealed that a pH of 11 was optimal for the recovery of SCFAs from algal sludge due to the higher cell disruption, suitable ORP condition for SCFAs production and inhibition of methanogens.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129954DOI Listing
February 2021

Combined cesarean delivery and repair of acute type A aortic dissection at advanced pregnancy.

J Card Surg 2021 Feb 24. Epub 2021 Feb 24.

Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China.

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http://dx.doi.org/10.1111/jocs.15300DOI Listing
February 2021

The discovery of SKLB-0335 as a paralog-selective EZH2 covalent inhibitor.

Chem Commun (Camb) 2021 Feb 24. Epub 2021 Feb 24.

State Key Laboratory of Biotherapy/Collaborative Innovation Center for Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, P. R. China.

By targeting the unique Cys663 of EZH2, SKLB-0335 displays high paralog-selectivity on EZH2. Biochemical studies show that SKLB-0335 can covalently bind to EZH2 at its S-adenosylmethionine (SAM) pocket and inhibit H3K27Me3. SKLB-0335 could be an effective chemical probe with which to further investigate the specific biological functions of EZH2.
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http://dx.doi.org/10.1039/d0cc04670aDOI Listing
February 2021

Proximate Quantum Spin Liquid on Designer Lattice.

Nano Lett 2021 Feb 22. Epub 2021 Feb 22.

Department of Physics and Astronomy, Rutgers University, Piscataway, New Jersey 08854, United States.

Complementary to bulk synthesis, here we propose a designer lattice with extremely high magnetic frustration and demonstrate the possible realization of a quantum spin liquid state from both experiments and theoretical calculations. In an ultrathin (111) CoCrO slice composed of three triangular and one kagome cation planes, the absence of a spin ordering or freezing transition is demonstrated down to 0.03 K, in the presence of strong antiferromagnetic correlations in the energy scale of 30 K between Co and Cr sublattices, leading to the frustration factor of ∼1000. Persisting spin fluctuations are observed at low temperatures via low-energy muon spin relaxation. Our calculations further demonstrate the emergence of highly degenerate magnetic ground states at the 0 K limit, due to the competition among multiply altered exchange interactions. These results collectively indicate the realization of a proximate quantum spin liquid state on the synthetic lattice.
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http://dx.doi.org/10.1021/acs.nanolett.0c04498DOI Listing
February 2021

hsa_circNFXL1_009 modulates apoptosis, proliferation, migration, and potassium channel activation in pulmonary hypertension.

Mol Ther Nucleic Acids 2021 Mar 28;23:1007-1019. Epub 2020 Sep 28.

School of Medicine, Nankai University, Tianjin, China.

In this study, we explored the circular RNA (circRNA) profile in pulmonary arterial hypertension (PAH) patients caused by chronic obstructive pulmonary disease (COPD) and the effects of hsa_circNFXL1_009 on abnormal proliferation, apoptosis, and migration of human pulmonary arterial smooth muscle cells (hPASMCs) driven by hypoxia. Using microarrays, we screened the circRNA profile in whole-blood samples from three pairs of subjects and found 158 dysregulated circRNAs in patients with PAH-COPD. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis further validated that hsa_circNFXL1_009 was dramatically downregulated with the highest area under a receiver operating characteristic curve (ROC) in 21 pairs of subjects. Consistently, exposure to hypoxia markedly reduced the hsa_circNFXL1_009 level in cultured hPASMCs. Delivery of exogenous hsa_circNFXL1_009 attenuated hypoxia-induced proliferation, apoptotic resistance, and migration of hPASMCs, as evidenced by immunocytochemistry, 5-ethynyl-2'-deoxyuridine incorporation, wound healing, and a TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling) assay. A luciferase assay showed that hsa_circNFXL1_009 directly sponged hsa-miR-29b-2-5p (miR-29b) and positively regulated the expression of voltage-gated potassium (K) channel subfamily B member 1 () at the mRNA level. Using patch-clamp electrophysiology, we proved that overexpression of hsa_circNFXL1_009 promoted a whole-cell K current in hPASMCs. Taken together, these studies identify hsa_circNFXL1_009 as a key regulator of PAH, and it may be used as a potential therapeutic target for the treatment of PAH.
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http://dx.doi.org/10.1016/j.omtn.2020.09.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868929PMC
March 2021

Extracellular vesicle YRNA in atherosclerosis.

Clin Chim Acta 2021 Feb 18;517:15-22. Epub 2021 Feb 18.

Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao Cancer Institute, Qingdao, Shandong 266071, China; School of Life Sciences, Tsinghua University, Beijing 100084, China. Electronic address:

Atherosclerosis is characterized by lipid accumulation and chronic inflammation. The accumulation of apoptotic foam cells can induce the secretion of proinflammatory factors and necrosis of atherosclerotic plaque tissue. Numerous studies have demonstrated that extracellular vesicle (EV)-enclosed YRNAs and their fragments, YsRNAs, play important roles in atherosclerosis initiation, progression, and diagnosis. YsRNA-5p transcripts promote foam cell apoptosis and inflammatory responses by binding to Ro60 in vitro and in vivo. YRNAs may regulate atherosclerosis progression by binding to several proteins, including nucleolin, Ro60, La, hnRNPK, hnRNPI, YBX1, and ELAVL1. Notably, YRNAs may be derived from miRNAs and piRNAs; in particular, Y4sRNA-3p and Y5sRNA-3p in humans are also called piR-hsa-32167 and piR-hsa-116589, respectively. In addition, EV-enclosed YRNAs are detectable in blood plasma, and YRNA ratios are potential biomarkers for inflammatory diseases, including atherosclerosis. YsRNAs are released by apoptotic macrophages into the blood of patients with coronary artery disease (CAD) and are potential biomarkers of foam cell apoptosis for monitoring atherosclerosis pathogenesis. Circulating YsRNAs are also present in EVs of platelets. Interestingly, gut microbes, which play a key role in the gut-heart axis and atherosclerosis progression, also express YRNAs and YsRNAs. Therefore, the gut microbiota may regulate the gut-heart axis and atherosclerosis progression via these YRNAs and YsRNAs. This review focuses on recent advances in our understanding of the potential roles and diagnostic values of YRNAs and YsRNAs in atherosclerosis and identifies new therapeutic and diagnostic targets for atherosclerosis.
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http://dx.doi.org/10.1016/j.cca.2021.02.003DOI Listing
February 2021

Health risk assessment based on source identification of heavy metals: A case study of Beiyun River, China.

Ecotoxicol Environ Saf 2021 Feb 16;213:112046. Epub 2021 Feb 16.

College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

Long-term retention and accumulation of heavy metals in rivers pose a great threat to the stability of ecosystems and human health. In this study, Beiyun River was taken as the example to quantitatively identify pollution sources and assess the pollution source-oriented health risk. A total of 8 heavy metals (Mn, Ni, Pb, Zn, As, Cr, Cd, and Cu) in Beiyun River were measured. Ordinary kriging (OK) and inverse distance weight (IDW) methods were used to predict the distribution of heavy metals. The results showed that the OK method is more accurate, and heavy metal pollution in the midstream and downstream is much more serious than that in the upstream. Principal component analysis-multiple linear regressions (PCA-MLR) and positive matrix factorization (PMF) methods were used to quantitatively identify pollution sources. The coefficient of determination (R) of PMF is closer to 1, and the analyzed pollution source is more refined. Furthermore, the result of source identification was imported into the health risk assessment to calculate the hazard index (HI) and carcinogenic risk (CR) of various pollution sources. The results showed that the HI and CR of As and Ni to local residents were serious in the Beiyun River. Industrial activities (23.0%) are considered to be the largest contribution of heavy metals in Beiyun River, followed by traffic source (17%), agricultural source (16%), and atmospheric deposition (16%). The source-oriented risk assessment indicated that the largest contribution of HI and CR is agricultural source in the Beiyun River, followed by industrial activities. This study provides a "target" for the precise control of pollution sources, which is of great significance for improving the fine management of the water environment in the basin.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112046DOI Listing
February 2021

Occurrence and ecological risk assessment of PPCPs in typical inflow rivers of Taihu lake, China.

J Environ Manage 2021 Feb 15;285:112176. Epub 2021 Feb 15.

School of Materials Science and Chemical Engineering, Anhui Jianzhu University, Hefei, 230022, China.

The occurrence and ecological risks of ten typical pharmaceutical and personal care products (PPCPs) at 12 typical inflow rivers of Taihu lake was investigated in this study. Seven out of the ten typical PPCPs targeted were detected in all the water samples and sediment samples tested. The PPCPs concentration detected were 0-94.91 ng/L for water samples and 0-18.27 ng/g for sediment samples. Sulfamethoxazole (SMZ) and erythromycin (ERY) has relatively higher concentration than other PPCPs in surface water samples, ciprofloxacin (CIP) and ofloxacin (OFX) has relatively higher concentration in the sediment samples. Inflow river-Caoqiao river has a relatively highest contamination of TN and TP, the PPCPs concentration in the river channel, estuary, lake-body also shows high value. This occurs in both the surface water and sediment sample, implied a relatively high pollution input from Caoqiao river. SMZ holds high long-term ecological risks in both surface water and sediment of almost all the tested inflow rivers of Taihu lake. Only ERY has medium short-term risks in surface water, other analyzed PPCPs hold low or insignificant short-terms risks for both surface water and sediments. This study fills the gap of PPCPs ecological risk of surface water and sediment of 12 typical inflow rivers of Taihu Lake, and revealed the importance of control sulfanilamide of the economic belt around Taihu Lake. The results of the present study are useful in providing information for PPCPs control and sustainable water management in freshwater lakes.
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http://dx.doi.org/10.1016/j.jenvman.2021.112176DOI Listing
February 2021

A review of distribution and risk of pharmaceuticals and personal care products in the aquatic environment in China.

Ecotoxicol Environ Saf 2021 Feb 15;213:112044. Epub 2021 Feb 15.

College of Chemical Engineering, Beijing University of Chemical Technology, Beijing 100029, PR China. Electronic address:

Due to the extensive use and pseudo-persistence of pharmaceuticals and personal care products (PPCPs), they are frequently detected in the aqueous environment, which has attracted global attention. In this paper, accumulation data of 81 PPCPs in surface water or sediment in China were reported. In addition, 20 kinds of PPCPs with high frequency were selected and their ecological risk assessment was conducted by risk quotient (RQs). The results indicated that the concentration detected in surface water and sediment ranged from ng/L (ng/kg) to μg/L (μg/kg) in China, which was similar to concentrations reported globally. However, contamination by certain PPCPs, such as caffeine, oxytetracycline, and erythromycin, was relatively high with a maximum concentration of more than 2000 ng/L in surface water. RQs revealed that 14 kinds of PPCPs pose no significant risk or low risk to aquatic organisms, while 6 kinds of PPCPs pose a high risk. Additionally, the pollution characteristics of PPCPs in each watershed are different. The Haihe River watershed and the central and lower Yangtze River were the regions of high concern for erythromycin. Triclosan has potential risks in the Pearl River watershed. This study determined the occurrence and risk of PPCPs in China in the past decade, providing a scientific basis for PPCPs pollution control and risk prevention.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112044DOI Listing
February 2021

Accurate Monitoring of Mitochondrial HO by Robust SERS Nanoprobes with a Au-Se Interface.

Anal Chem 2021 Mar 18;93(8):4059-4065. Epub 2021 Feb 18.

College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.

Mitochondrial redox homeostasis plays a vital role in many biological processes. Hydrogen peroxide (HO), one of the most important components for the balance between oxidizing species and reducing species, also acts as the messenger of mitochondrial damage. Thus, an accurate quantitative detection of HO in mitochondria is very important for the evaluation of mitochondrial redox homeostasis. Here, we develop robust surface-enhanced Raman spectroscopy (SERS) nanoprobes based on Au nanoparticles as SERS substrate and functionalized carrier, which is further modified with a phenylboronic acid pinacol ester for specific HO response and a location peptides for mitochondrial targeting by creating a robust Au-Se interface. The SERS nanoprobes show good resistance to abundant thiol under biological conditions and superior performance for mitochondria HO monitoring in living cells than the SERS nanoprobes with the traditional Au-S interface, which enables us to achieve quantification of mitochondrial HO and obtain its real-time dynamic change under oxidative stress.
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http://dx.doi.org/10.1021/acs.analchem.0c05065DOI Listing
March 2021

Amphiphilic Janus nanoparticles for imaging-guided synergistic chemo-photothermal hepatocellular carcinoma therapy in the second near-infrared window.

Nanoscale 2021 Feb;13(7):3974-3982

Department of Chemistry, Northeast Normal University, 5268 Renmin Street, Changchun, Jilin 130024, P. R. China.

Hepatocellular carcinoma (HCC) is one of the most common and deadly malignant tumors worldwide. With unsatisfactory effects of traditional systematic chemotherapy for HCC owing to its drug resistance, novel therapeutic strategies based on nanomaterials for HCC treatments are promising solutions. To solve the challenges of nanoparticles (NPs)-based drug delivery systems for potential clinical applications, we designed water soluble amphiphilic oleic acid-NaYF4:Yb,Er/polydopamine Au nanoflower Janus NPs (OA-UCNPs/PDA-AuF JNPs) with discrete multi compartment nanostructures as dual-drug delivery systems (DDDSs). This unique nanostructure meets the requirements for containing hydrophobic hydroxycamptothecin/hydrophilic doxorubicin in divided spaces and releasing each drug from non-interfering channels under pH/near-infrared (NIR) dual-stimuli. The amphiphilic DDDSs were utilized to eradicate the tumor burden on a high-fidelity HCC model of a patient-derived xenograft (PDX), and represented an efficient strategy for defeating HCC using multi-modal imaging-guided dual-drug chemo-photothermal therapy in the second NIR window. In addition, the potential mechanisms of action for the DDDSs were evaluated.
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http://dx.doi.org/10.1039/d0nr09017dDOI Listing
February 2021

Narrow Leaf21, Encoding Ribosomal Protein RPS3A, Controls Leaf Development in Rice.

Plant Physiol 2021 Feb 16. Epub 2021 Feb 16.

National Key Facility for Crop Gene Resources and Genetic Improvement, Institute of Crop Sciences, Chinese Academy of Agricultural Sciences, Beijing 100081, China.

Leaf morphology influences photosynthesis, transpiration and ultimately crop yield. However, the molecular mechanism of leaf development is still not fully understood. Here, we identified and characterized the narrow leaf21 (nal21) mutant in rice (Oryza sativa), showing a significant reduction in leaf width, leaf length and plant height, and increased tiller number. Microscopic observation revealed defects in the vascular system and reduced epidermal cell size and number in the nal21 leaf blade. Map-based cloning revealed that NAL21 encodes a ribosomal small subunit protein RPS3A. Ribosome-targeting antibiotics resistance assay and ribosome profiling showed a significant reduction in the free 40S ribosome subunit in the nal21 mutant. The nal21 mutant showed aberrant auxin responses in which multiple auxin response factors (ARFs) harboring upstream open reading frames (uORFs) in their 5'-untranslated region (5'-UTR) were repressed at the translational level. The WUSCHEL-related homeobox 3A (OsWOX3A) gene, a key transcription factor involved in leaf blade lateral outgrowth, is also under the translational regulation by RPS3A. Transformation with modified OsARF11, OsARF16 and OsWOX3A genomic DNA lacking uORFs rescued the narrow leaf phenotype of nal21 to a better extent than transformation with their native genomic DNA, implying that RPS3A could regulate translation of ARFs and WOX3A through uORFs. Our results demonstrate that proper translational regulation of key factors involved in leaf development is essential to maintain normal leaf morphology.
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http://dx.doi.org/10.1093/plphys/kiab075DOI Listing
February 2021

Transcriptomic analysis of endometrial receptivity for a genomic diagnostics model of Chinese women.

Fertil Steril 2021 Feb 12. Epub 2021 Feb 12.

Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People's Republic of China; Key Laboratory of Female Reproductive Endocrine Related Diseases, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People's Republic of China. Electronic address:

Objective: To define the transcriptomic signature with respect to human endometrial receptivity in Chinese women by next-generation sequencing and to develop a more refined and customized bioinformatic predictive method for endometrial dating in Chinese women.

Design: Randomized.

Setting: A tertiary hospital-based reproductive medicine center.

Patient(s): Ninety healthy, fertile Chinese women.

Intervention(s): Human endometrial biopsies.

Main Outcome Measure(s): Gene expression of endometrial biopsies.

Result(s): Ninety endometrial samples from healthy Chinese women during their menstrual cycles-including prereceptive (luteinizing hormone [LH] + 3 days/LH + 5 days), receptive (LH + 7 days), and post-receptive (LH + 9 days) phases-were subjected to transcriptomic analysis using messenger RNA (mRNA)-enriched RNA-Seq. Feature genes were obtained and used to train the predictor for endometrial dating, with 63 samples for the training set and 27 samples for the validation set. Differentially expressed genes (DEGs) were identified by comparing samples from different phases of the menstrual cycle. Based on the transcriptomic feature genes, we constructed a bioinformatic predictor for endometrial dating. The accuracy on assessment of the endometrium on days LH + 3, LH + 5, LH + 7, and LH + 9 was 100% in the training set and 85.19% in the validation set.

Conclusion(s): Our transcriptomic profiling method can be used to monitor the window of implantation with regard to the endometrium in the Chinese population. This method potentially provides an evaluation of endometrial status, and can be used to predict a personal window of implantation by reproductive medicine clinicians.
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http://dx.doi.org/10.1016/j.fertnstert.2020.11.010DOI Listing
February 2021

Corticosterone-induced Hippocampal 5-HT Responses were Muted in Depressive-like State.

ACS Chem Neurosci 2021 Mar 15;12(5):845-856. Epub 2021 Feb 15.

Department of Clinical Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, China.

Interactions between the hypothalamic-pituitary-adrenal axis and the central 5-HT system in the depressive state remain largely unknown. The present study investigated corticosterone (CORT) regulations of extracellular 5-HT in the hippocampal CA3 in a mouse model of depression. Basal dialysate 5-HT, true extracellular 5-HT, 5-HT reuptake efficiency, and time courses of dialysate 5-HT following CORT injections at 10, 20, and 40 mg/kg were determined at baseline, depressive-like state and after subsequent fluoxetine (FLX) treatment using microdialysis in male C57BL/6 mice. Behavioral tests were used to determine behavioral phenotypes and therapeutic responses to FLX. Depressed mice showed decreased extracellular 5-HT, increased 5-HT reuptake efficiency, and absence of the increase in dialysate 5-HT response to CORT injections, which were all reversed in FLX-responsive mice. Surprisingly, the FLX nonresponsive mice continued to worsen behaviorally and exhibited lower extracellular 5-HT and higher 5-HT reuptake efficiency. Our study indicates that abolished-CORT induced 5-HT response, decreased extracellular 5-HT, and increased 5-HT reuptake efficiency might be the signature features associated with depressive-like state. Increased 5-HT reuptake efficiency was one of the underlying mechanisms, with target effectors remaining to be explored. The findings in the FLX nonresponsive mice suggest distinct neuromechanisms, which might be genetically predetermined.
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http://dx.doi.org/10.1021/acschemneuro.0c00334DOI Listing
March 2021

In vitro analysis of a physiological strain sensor formulated from a PEDOT:PSS functionalized carbon nanotube-poly(glycerol sebacate urethane) composite.

Mater Sci Eng C Mater Biol Appl 2021 Feb 6;121:111857. Epub 2021 Jan 6.

Centre for Research in Medical Devices, National University of Ireland, Galway, Ireland. Electronic address:

Biodegradable strain sensors able to undergo controlled degradation following implantation have recently received significant interest as novel approaches to detect pathological tissue swelling or non-physiological stresses. In this study, the physicomechanical, electrochemical and active pressure sensing behavior of an electrically conductive and biodegradable poly(glycerol sebacate urethane) (PGSU) composite, reinforced with poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) functionalized carbon nanotubes (CNTs), was evaluated in vitro. Analysis of these PGSU-CNTs composites demonstrated that the incorporation of functionalized CNTs into a biodegradable elastomer resulted in enhanced mechanical strength, conductivity and tailored matrix biodegradation. PGSU-CNT composites were subsequently formulated into flexible and active pressure sensors which demonstrated optimal sensitivity to applied 1% uniaxial tensile strains. Finally, cytocompatibility analysis a with primary neural culture confirmed that PGSU-CNT composites exhibited low cytotoxicity, and supported neuron adhesion, viability, and proliferation in vitro.
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http://dx.doi.org/10.1016/j.msec.2020.111857DOI Listing
February 2021

Acupuncture for diabetic neurogenic bladder: A protocol for systematic review and meta-analysis.

Medicine (Baltimore) 2021 Feb;100(6):e24573

Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan Province, China.

Background: Diabetic neurogenic bladder (DNB) is one of the common complications of diabetes mellitus, which has a high prevalence rate. Some research suggested that acupuncture can improve the clinical symptoms of diabetic neurogenic bladder patients, but there is no systematic review or meta-analysis to assess this therapy. Therefore, this study aims to explore the effectiveness and safety of acupuncture for patients with DNB.

Methods: In this study, we will search for electronic databases including the Cochrane Library, Web of Science, PubMed, MEDLINE, EMBASE,China National Knowledge Infrastructure (CNKI), Wan-Fang, and Baidu Scholar Database from inception to December 2020. We will select randomized controlled trials that have been published in English or Chinese related to acupuncture for DNB. Selection of study, extraction of data, and assessment of study quality will be performed independently by 2 researchers, and we will use Revman 5.3 software which is provided by Cochrane assistance network, to perform the data analysis.

Results: This study will provide evidence of the effectiveness and safety of acupuncture for DNB.

Conclusion: This study will clarify whether acupuncture is an effective treatment for DNB, and will also provide a reference for clinical practice and guidelines development.
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http://dx.doi.org/10.1097/MD.0000000000024573DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7886445PMC
February 2021

Rosuvastatin exerts anti-atherosclerotic effects by improving macrophage-related foam cell formation and polarization conversion via mediating autophagic activities.

J Transl Med 2021 Feb 10;19(1):62. Epub 2021 Feb 10.

Department of Cardiology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Background: Atherosclerosis is a chronic vascular disease posing a great threat to public health. We investigated whether rosuvastatin (RVS) enhanced autophagic activities to inhibit lipid accumulation and polarization conversion of macrophages and then attenuate atherosclerotic lesions.

Methods: All male Apolipoprotein E-deficient (ApoE) mice were fed high-fat diet supplemented with RVS (10 mg/kg/day) or the same volume of normal saline gavage for 20 weeks. The burden of plaques in mice were determined by histopathological staining. Biochemical kits were used to examine the levels of lipid profiles and inflammatory cytokines. The potential mechanisms by which RVS mediated atherosclerosis were explored by western blot, real-time PCR assay, and immunofluorescence staining in mice and RAW264.7 macrophages.

Results: Our data showed that RVS treatment reduced plaque areas in the aorta inner surface and the aortic sinus of ApoE mice with high-fat diet. RVS markedly improved lipid profiles and reduced contents of inflammatory cytokines in the circulation. Then, results of Western blot showed that RVS increased the ratio LC3II/I and level of Beclin 1 and decreased the expression of p62 in aortic tissues, which might be attributed to suppression of PI3K/Akt/mTOR pathway, hinting that autophagy cascades were activated by RVS. Moreover, RVS raised the contents of ABCA1, ABCG1, Arg-1, CD206 and reduced iNOS expression of arterial wall, indicating that RVS promoted cholesterol efflux and M2 macrophage polarization. Similarly, we observed that RVS decreased lipids contents and inflammatory factors expressions in RAW264.7 cells stimulated by ox-LDL, accompanied by levels elevation of ABCA1, ABCG1, Arg-1, CD206 and content reduction of iNOS. These anti-atherosclerotic effects of RVS were abolished by 3-methyladenine intervention. Moreover, RVS could reverse the impaired autophagy flux in macrophages insulted by chloroquine. We further found that PI3K inhibitor LY294002 enhanced and agonist 740 Y-P weakened the autophagy-promoting roles of RVS, respectively.

Conclusions: Our study indicated that RVS exhibits atheroprotective effects involving regulation lipid accumulation and polarization conversion by improving autophagy initiation and development via suppressing PI3K/Akt/mTOR axis and enhancing autophagic flux in macrophages.
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http://dx.doi.org/10.1186/s12967-021-02727-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877030PMC
February 2021

Effect of critical illness insurance on the medical expenditures of rural patients in China: an interrupted time series study for universal health insurance coverage.

BMJ Open 2021 Feb 8;11(2):e036858. Epub 2021 Feb 8.

School of Medicine and Health Management, Huazhong University of Science and Technology Tongji Medical College, Wuhan, China

Objective: The objective of this study is to determine if critical illness insurance (CII) promotes the universal health coverage to reduce out-of-pocket (OOP) medical expenditures and improve the effective reimbursement rate (ERR) in rural China.

Study Design: The 5-year monthly hospitalisation data, starting 2 years before the CII (ie, the 'intervention') began, were collected. Interrupted time series analysis models were used to evaluate the immediate and gradual effects of CII on OOP payment and ERR.

Setting: The study was conducted in Xiantao County, Hubei Province, China.

Participants: A total of 511 221 inpatients within 5 years were included in the analysis.

Results: In 2016, 100 288 patients received in-patient services, among which 4137 benefited from CII. After the implementation of CII, OOP expenses increased 32.2% (95% CI 24.8% to 39.5%, p<0.001). Compared with the preintervention periods, the trend changes decline at a rate of 0.7% per month after the implementation of CII. Similarly, a significant decrease was observed in log ERR after the intervention started. The rate of level change is 16% change (95% CI -20.0% to -12.1%, p<0.001).

Conclusion: CII did not decrease the OOP payments of rural inpatients in 2011-2016 periods. The limited extents of population coverage and financing resources can be attributed to these results. Therefore, the Chinese government must urgently raise the funds of CII and improve the CII policy reimbursement rate.
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http://dx.doi.org/10.1136/bmjopen-2020-036858DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871675PMC
February 2021

Regulatory Master Genes Identification and Drug Repositioning by Integrative mRNA-miRNA Network Analysis for Acute Type A Aortic Dissection.

Front Pharmacol 2020 21;11:575765. Epub 2021 Jan 21.

Department of Clinical Pharmacy, The First Affiliated Hospital, College of Medicine, Zhejiang University, Zhejiang, China.

Acute type A aortic dissection (ATAAD) is a life-threatening disease. The understanding of its pathogenesis and treatment approaches remains unclear. In the present work, differentially expressed genes (DEGs) from two ATAAD datasets GSE52093 and GSE98770 were filtered. Transcription factor TEAD4 was predicted as a key modulator in protein-protein interaction (PPI) network. Weighted correlation network analysis (WGCNA) identified five modules in GSE52093 and four modules in GSE98770 were highly correlated with ATAAD. 71 consensus DEGs of highly correlated modules were defined and functionally annotated. L1000CDS was executed to predict drug for drug repositioning in ATAAD treatment. Eight compounds were filtered as potential drugs. Integrative analysis revealed the interaction network of five differentially expressed miRNA and 16 targeted DEGs. Finally, master DEGs were validated in human ATAAD samples and AD cell model . TIMP3 and SORBS1 were downregulated in ATAAD samples and AD cell model, while PRUNE2 only decreased . Calcium channel blocker and glucocorticoid receptor agonist might be potential drugs for ATAAD. The present study offers potential targets and underlying molecular mechanisms ATAAD pathogenesis, prevention and drug discovery.
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http://dx.doi.org/10.3389/fphar.2020.575765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861055PMC
January 2021

Aberrant monocyte subsets in patients with Behçet's disease.

Clin Immunol 2021 Feb 5;225:108683. Epub 2021 Feb 5.

Department of Rheumatology and Clinical Immunology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Peking Union Medical College, The Ministry of Education Key Laboratory, National Clinical Research Center for Dermatologic and Immunologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Shuaifuyuan, Dongcheng District, Beijing 100730, China. Electronic address:

Monocytes are a versatile and dynamic population, but its implication in Behçet's Disease (BD) remains elusive. We investigated the proportion, phenotypical and functional alterations in classical monocytes (CM), intermediate monocytes (IM) and non-classical monocytes (NCM) subsets in BD. A higher IM and lower NCM population in BD patients were noted, closely correlated with disease activity, and rescued after treatment. CD11b and CD64 expression on CM, IM and NCM in BD were enhanced. BD CM promoted TNF-a and IL-6 production and facilitated Th1 differentiation. BD IM promoted IL-6 production. We further demonstrated a higher level of phosphorylated p65 (p-p65) in BD CM and increased p-p65 and p-p38 in BD IM. Our data highlighted the aberrant populations of IM and CM in BD, potentially implicated in BD' pathogenesis.
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http://dx.doi.org/10.1016/j.clim.2021.108683DOI Listing
February 2021