Publications by authors named "Tao Zhuang"

47 Publications

LARP7 ameliorates cellular senescence and aging by allosterically enhancing SIRT1 deacetylase activity.

Cell Rep 2021 Nov;37(8):110038

Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Department of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Shanghai Jiao Tong University, 800 Dong Chuan Road, Shanghai 200240, China. Electronic address:

Cellular senescence is associated with pleiotropic physiopathological processes, including aging and age-related diseases. The persistent DNA damage is a major stress leading to senescence, but the underlying molecular link remains elusive. Here, we identify La Ribonucleoprotein 7 (LARP7), a 7SK RNA binding protein, as an aging antagonist. DNA damage-mediated Ataxia Telangiectasia Mutated (ATM) activation triggers the extracellular shuttling and downregulation of LARP7, which dampens SIRT1 deacetylase activity, enhances p53 and NF-κB (p65) transcriptional activity by augmenting their acetylation, and thereby accelerates cellular senescence. Deletion of LARP7 leads to senescent cell accumulation and premature aging in rodent model. Furthermore, we show this ATM-LARP7-SIRT1-p53/p65 senescence axis is active in vascular senescence and atherogenesis, and preventing its activation substantially alleviates senescence and atherogenesis. Together, this study identifies LARP7 as a gatekeeper of senescence, and the altered ATM-LARP7-SIRT1-p53/p65 pathway plays an important role in DNA damage response (DDR)-mediated cellular senescence and atherosclerosis.
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http://dx.doi.org/10.1016/j.celrep.2021.110038DOI Listing
November 2021

Efficacy of integrated Traditional Chinese Medicine and anti-retroviral therapy on immunological nonresponse in patients with human immunodeficiency virus/acquired immunodeficiency syndrome: a Meta-analysis of randomized controlled trial.

J Tradit Chin Med 2021 Oct;41(5):669-676

Research Center of AIDS Treatment with Traditional Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing 100700, China.

Objective: To explore the efficacy of integrating Traditional Chinese Medicine (TCM) and anti-retroviral therapy (ART), a customized combination of different classes of medications which was also called cock-tail treatment, on the immunological nonresponse (INR) in people living with human immunodeficiency virus (HIV) (PLWH).

Methods: Relevant literature in databases such as China National Knowledge Infrastructure Database (CNKI), Wanfang Digital Journal, Chinese Medical Journal Database (CMJD), Chinese Biomedical Literature Database (CBM), PubMed, Cochrane, and Embase was reviewed by two independent investigators. Data were extracted from the studies according to the eligible criteria and analyzed using Review Manager 5.3.

Results: Nine randomized controlled trials (RCTs) with 1078 patients were analyzed. Our analyses showed that CD4 T cell counts in the treatment group improved compared with that in the control group [mean difference (MD) = 13.51, 95% confidence interval (CI): 7.42-19.60, P < 0.0001]. There was no significant difference between the treated and control groups after 3 months (MD = 25.31, 95% CI: ?2.78 to 53.41, P = 0.08). However, after 6 and 12 months, the response of the treatment group was superior to the control group (MD = 27.45, 95% CI: 7.09-47.81, P = 0.008 and MD = 27.34, 95% CI: 6.31-48.37, P = 0.01, respectively). The clinical efficacy of the treatment group was also higher than that of the control group (RR = 1.75, 95% CI: 1.16-2.65, P = 0.007). However, CD45RO and CD45RA T cell counts did not differ significantly between the two groups (MD = 12.37, 95% CI: ?6.71 to 31.45, P = 0.20 and MD = 5.67, 95% CI: ?3.00 to14.35, P = 0.20, respectively).

Conclusion: The combined treatment strategy of integrated TCM and Western Medicine promotes long-term reconstitution of the immune system and thus, is beneficial and has potential use for improving INR in PLWH. However, large-scale RCTs are required to provide evidence for optimal intervention strategies.
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http://dx.doi.org/10.19852/j.cnki.jtcm.2021.05.002DOI Listing
October 2021

Optimization of bifunctional piperidinamide derivatives as σR Antagonists/MOR agonists for treating neuropathic pain.

Eur J Med Chem 2021 Dec 4;226:113879. Epub 2021 Oct 4.

Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China; Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China. Electronic address:

Here, we describe the optimization, synthesis, and associated pharmacological analgesic activities of a new series of bifunctional piperidinamide derivatives as sigma-1 receptor (σR) antagonists and mu opioid receptor (MOR) agonists. The new compounds were evaluated in vitro in σR and MOR binding assays. The most promising compound 114 (also called HKC-126), showed superior affinities for σR and MOR and good selectivity to additional receptors related to pain. Compound 114 showed powerful dose-dependent analgesic effects in the acetic acid writhing test, formalin test, hot plate test, and chronic constriction injury (CCI) neuropathic pain model. In contrast to an equianalgesic dose of fentanyl, compound 114 produced fewer opioid-like side effects, such as reward liability, respiratory depression, physical dependence, and sedation. Lastly, the pharmacokinetic properties of this drug were also acceptable, and these results suggest that compound 114, as a mixed σR/MOR ligand, has potential for treating neuropathic pain.
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http://dx.doi.org/10.1016/j.ejmech.2021.113879DOI Listing
December 2021

Effect of carbon nitride synthesized by different modification strategies on the performance of carbon nitride/PVDF photocatalytic composite membranes.

J Hazard Mater 2022 Jan 10;422:126877. Epub 2021 Aug 10.

Jinan Environmental Research Academy, Jinan 250102, China.

Carbon nitride (CN)/polyvinylidene fluoride (PVDF) photocatalytic composite membrane (PCM) is considered as a promising candidate to improve the anti-fouling characteristic of conventional PVDF membrane and overcome the difficulty encountered during recovery of powder catalyst simultaneously. However, the effects of differently-modified CN on PCM and its mechanism are still unclear. In this study, bulk-CN (BCN), carbon defects CN (CCN), nitrogen defect CN (DCN), mesoporous CN (MCN), and nitrogen-rich CN (NCN) were incorporated into PVDF by phase inversion method. The influence of changes in the physical and chemical properties of CN, including hydrophilic groups, photocatalytic activity, and particle size, on the permeability, anti-fouling characteristic, and photocatalytic self-cleaning activity of CN/PVDF was systematically analyzed. The mechanism of excellent performance of PCM was revealed by experimental test and theoretical calculation. The flux of PCM was significantly improved by increasing the hydrophilic group on modified CN. However, the differences in particle size and interaction between different types of modified CN and PVDF chains endowed the CN/PVDF with different porosity. DCN/PVDF showed high porosity and hydrophilicity, leading to high water flux and rejection rate of 293.6 L (m h) and 90.1%, respectively. Compared to pure PVDF, the flux recovery rate of DCN/PVDF increased by 27.6%, and the irreversible fouling decreased from 36.9% to 9.2%. The modified CN/PVDF showed excellent photocatalytic activity for the removal of cefotaxime (CFX) and E. coli. Owing to the narrow band gap of DCN, large specific surface area, and low photogenerated carrier recombination rate, the CFX removal rate reached 99% in 2 h, and E. coli inactivation achieved 3.7 log within 4 h via DCN/PVDF.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126877DOI Listing
January 2022

Do positive allosteric modulators (PAMs) of the MOR exert antinociception with reduced side effects under pathological conditions?

Proc Natl Acad Sci U S A 2021 07;118(28)

Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China;

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http://dx.doi.org/10.1073/pnas.2107784118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8285981PMC
July 2021

Bifunctional μ opioid and σ receptor ligands as novel analgesics with reduced side effects.

Eur J Med Chem 2021 Nov 18;223:113658. Epub 2021 Jun 18.

Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China. Electronic address:

Opioid analgesics are highly effective painkillers for the treatment of moderate or severe pain, but they are associated with a number of undesirable adverse effects, including the development of tolerance, addiction, constipation and life-threatening respiratory depression. The development of new and safer analgesics with innovative mechanisms of action, which can enhance the efficacy in comparison to available treatments and reduce their side effects, is urgently needed. The sigma-1 receptor (σR), a unique Ca-sensing chaperone protein, is expressed throughout pain-modulating tissues and affects neurotransmission by interacting with different protein partners, including molecular targets that participate in nociceptive signalling, such as the μ-opioid receptor (MOR), N-methyl-d-aspartate receptor (NMDAR) and cannabinoid 1 receptor (CBR). Overwhelming pharmacological and genetic evidence indicates that σR antagonists induce anti-hypersensitive effects in sensitising pain conditions (e.g. chemically induced, inflammatory and neuropathic pain) and enhance opioid analgesia but not opioid-mediated detrimental effects. It has been suggested that balanced modulation of MORs and σRs may improve both the therapeutic efficacy and safety of opioids. This review summarises the functional profiles of ligands with mixed MOR agonist and σR antagonist activities and highlights their therapeutic potentials for pain management. Dual MOR agonism/σR antagonism represents a promising avenue for the development of potent and safer analgesics.
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http://dx.doi.org/10.1016/j.ejmech.2021.113658DOI Listing
November 2021

Pdcd10-Stk24/25 complex controls kidney water reabsorption by regulating Aqp2 membrane targeting.

JCI Insight 2021 06 22;6(12). Epub 2021 Jun 22.

Department of Pharmacology, School of Basic Medical Sciences, Tianjin Medical University, China.

PDCD10, also known as CCM3, is a gene found to be associated with the human disease cerebral cavernous malformations (CCMs). PDCD10 forms a complex with GCKIII kinases including STK24, STK25, and MST4. Studies in C. elegans and Drosophila have shown a pivotal role of the PDCD10-GCKIII complex in maintaining epithelial integrity. Here, we found that mice deficient of Pdcd10 or Stk24/25 in the kidney tubules developed polyuria and displayed increased water consumption. Although the expression levels of aquaporin genes were not decreased, the levels of total and phosphorylated aquaporin 2 (Aqp2) protein in the apical membrane of tubular epithelial cells were decreased in Pdcd10- and Stk24/25-deficient mice. This loss of Aqp2 was associated with increased expression and membrane targeting of Ezrin and phosphorylated Ezrin, Radixin, Moesin (p-ERM) proteins and impaired intracellular vesicle trafficking. Treatment with Erlotinib, a tyrosine kinase inhibitor promoting exocytosis and inhibiting endocytosis, normalized the expression level and membrane abundance of Aqp2 protein, and partially rescued the water reabsorption defect observed in the Pdcd10-deficient mice. Our current study identified the PDCD10-STK-ERM signaling pathway as a potentially novel pathway required for water balance control by regulating vesicle trafficking and protein abundance of AQP2 in the kidneys.
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http://dx.doi.org/10.1172/jci.insight.142838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8262504PMC
June 2021

Antibiotic residues in wastewaters from sewage treatment plants and pharmaceutical industries: Occurrence, removal and environmental impacts.

Sci Total Environ 2021 Sep 17;788:147811. Epub 2021 May 17.

Beijing Key Laboratory of Aqueous Typical Pollutants Control and Water Quality Safeguard, School of Civil Engineering, Beijing Jiaotong University, Beijing 100044, China.

Sewage treatment plants (STPs) and pharmaceutical manufactories (PMFs) are recognized as important reservoirs for aquatic pollution with antibiotics. Although the occurrence of multiple classes of antibiotics has been mostly reported for STPs and PMFs, knowledge on the effects of wastewater treatment processes on the removal of antibiotics is not well documented. In this study, wastewaters were collected from different treatment points of two STPs and two PMFs in eastern China. Thirty-seven antibiotics within the four classes of fluoroquinolones (FQs), macrolides (MACs), sulfonamides (SAs) and tetracyclines (TCs) were analyzed. Among the investigated antibiotics, 19-33 out of 37 target compounds were detected at least once in the STPs wastewaters ranging from low ng/L to approximately 12.7 μ/L. In the wastewater samples collected from PMFs, up to 34 antibiotics were present with detection frequencies up to 100%, showing generally higher concentrations (up to 19.0 μ/L) than those at the STPs. FQs and SAs were the dominant antibiotic families, which accounted for more than 90% of the total antibiotic concentration in the wastewaters. Moreover, the removal of antibiotics by anaerobic-anoxic-oxic (AO), membrane bioreactor (MBR) and conventional activated sludge (CAS) systems was evaluated. The MBR system exhibited the best performance, mainly due to the processes of biodegradation and sorption during biological treatments. Notably, several SAs (SMP, SMZ) and FQs (CIN, ENO) antibiotics were consistently detected at concentration levels of μ/L in the effluent samples. The culturable antibiotic-resistance tests and risk assessment indicated that the antibiotic-contaminated effluents would facilitate the development of resistant bacteria and pose high toxicity to non-target organisms in the aquatic environment. Overall, the findings suggested an urgent need for improving the wastewater treatment technologies for simultaneous removal of different classes of antibiotics.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147811DOI Listing
September 2021

Isolation, structural characterization and quality control strategy of an unknown process-related impurity in sugammadex sodium.

J Pharm Biomed Anal 2021 Jun 15;200:114072. Epub 2021 Apr 15.

Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan, 430074, China; Jiangsu Key Laboratory of Marine Biological Resources and Environment, Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, School of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China. Electronic address:

Sugammadex sodium is the first selective relaxant binding agent (SRBA) indicated for reversal of neuromuscular blockade induced by rocuronium or vecuronium during surgery. The chemical synthesis of sugammadex involved the nucleophilic substitution reaction between 6-per-deoxy-6-per-halo-γ-cyclodextrin and 3-mercaptopropionic acid under basic conditions. During the manufacture of sugammadex sodium, an unknown process-related impurity was observed in pilot batches in the range of 0.21-1.9 % based upon HPLC analysis. The same impurity was also detected in commercial Bridion® samples at the levels of more than 0.1 %. Thus this unknown impurity was enriched from the mother liquor of reaction by preparative HPLC and characterized by LC-MS/QTOF, 1D-NMR (H, C, DEPTQ) and 2D-NMR (H-H COSY, TOCSY, HSQC, HMBC, NOESY) techniques. Based on spectroscopic analysis and the synthetic route of sugammadex sodium, this new impurity was identified as monocyanoethyl sugammadex (impurity-I). The prospects to the formation mechanism and control strategy of impurity-I were discussed in detail. Moreover, the toxicological properties of impurity-I were evaluated using ADMET Predictor® software.
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http://dx.doi.org/10.1016/j.jpba.2021.114072DOI Listing
June 2021

A Stronger Association of Epicardial Fat Volume with Non-Valvular Atrial Fibrillation Than Measures of General Obesity in Chinese Patients Undergoing Computed Tomography Coronary Angiography.

Diabetes Metab Syndr Obes 2021 18;14:1223-1232. Epub 2021 Mar 18.

Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China.

Objective: An association of atrial fibrillation (AF) with epicardial fat volume (EFV) varied in different ethnic groups. We evaluated the AF-related risk factors and its association with pericardial fat in Chinese patients.

Methods: Patients referred for coronary computed tomography angiography (CCTA) in Shanghai East Hospital during 2012 to 2014 (n=2042, 43.8% women, mean age 65.0 years) had AF and cardiovascular risk assessment. Pericardial fat depots were measured from CT and the association of EFV with non-valvular AF risk factors was evaluated by multivariate logistic regression models.

Results: AF was present in 8.5% of patients with 11.6% of AF patients having rheumatic heart disease (RHD) and 8.7% having other valvular diseases. With increasing age, the proportion of RHD-related AF decreased and the risk factors for non-valvular AF increased. There was a significantly higher proportion of risk factors for non-valvular AF in men than in women (p=0.008), but RHD-related AF was more prevalent in women than men (p=0.013). The patients with non-valvular AF had significantly higher BMI and EFV with more pronounced elevation of EFV (p<0.001). Multivariate logistic regression showed a significant association of EFV with AF after adjustment for BMI and clinical risk factors, and the highest EFV quartile was associated with AF independent of left atrial size and obstructive coronary artery disease.

Conclusion: The association of EFV with non-valvular AF in Chinese patients was independent of generalized adiposity and clinical risk factors especially in highest EFV quartile. These findings support the growing appreciation of the association of EFV with AF.
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http://dx.doi.org/10.2147/DMSO.S274047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7987254PMC
March 2021

Synthesis and biological activities of novel mitochondria-targeted artemisinin ester derivatives.

Bioorg Med Chem Lett 2021 05 7;39:127912. Epub 2021 Mar 7.

Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province, Department of Pharmacy, School of Medicine, Hunan Normal University, Changsha, Hunan, China. Electronic address:

A series of novel artemisinin ester derivatives were designed and synthesized for targeting mitochondria. Cytotoxicity against SMMC-7721, HepG2, OVCAR3, A549 and J82 cancer cell lines was evaluated. Compound 2c (IC = 3.0 μM) was the most potent anti-proliferative molecule against the OVCAR3 cells with low cytotoxicity in normal HUVEC cells. The mechanism of action of compound 2c was further investigated by analyzing cell apoptosis, mitochondrial membrane potential (Δψm) and intracellular ROS generation. The results indicated that compound 2c targeted mitochondria and induced cell apoptosis. ROS and heme attributed to the cytotoxicity and cell apoptosis of compound 2c. These promising findings indicated the compound 2c could serve as a great candidate against ovarian cancer for further investigation.
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http://dx.doi.org/10.1016/j.bmcl.2021.127912DOI Listing
May 2021

LARP7 Protects Against Heart Failure by Enhancing Mitochondrial Biogenesis.

Circulation 2021 May 5;143(20):2007-2022. Epub 2021 Mar 5.

Key Laboratory of Systems Biomedicine, Shanghai Center for Systems Biomedicine, Department of Pediatric Cardiology, Xin Hua Hospital, School of Medicine, Xin Hua Hospital, Shanghai Jiao Tong University, China (H.J.Y., F.Z., P.Y.Y., S.S.Z., Y.M.L., Z.L.G., Z.X.L., Y.J.X., Y.N.L., K.S., B.Z.).

Background: Heart failure (HF) is among the leading causes of morbidity and mortality, and its prevalence continues to rise. LARP7 (La ribonucleoprotein domain family member 7) is a master regulator that governs the DNA damage response and RNAPII (RNA polymerase II) pausing pathway, but its role in HF pathogenesis is incompletely understood.

Methods: We assessed LARP7 expression in human HF and in nonhuman primate and mouse HF models. To study the function of LARP7 in heart, we generated global and cardiac-specific knockout mice. We acutely abolished LARP7 in mature cardiomyocytes by Cas9-mediated somatic knockout. We overexpressed LARP7 in cardiomyocytes using adeno-associated virus serotype 9 and ATM (ataxia telangiectasia mutated protein) inhibitor. The therapeutic potential of LARP7-regulated pathways in HF was tested in a mouse myocardial infarction model.

Results: LARP7 was profoundly downregulated in failing human hearts and in nonhuman primate and murine hearts after myocardial infarction. Low LARP7 levels in failing hearts were linked to elevated reactive oxygen species, which activated the ATM-mediated DNA damage response pathway and promoted LARP7 ubiquitination and degradation. Constitutive knockout in mouse resulted in impaired mitochondrial biogenesis, myocardial hypoplasia, and midgestational lethality. Cardiac-specific inactivation resulted in defective mitochondrial biogenesis, impaired oxidative phosphorylation, elevated oxidative stress, and HF by 4 months of age. These abnormalities were accompanied by reduced SIRT1 (silent mating type information regulation 2 homolog 1) stability and deacetylase activity that impaired SIRT1-mediated transcription of genes for oxidative phosphorylation and energy metabolism and dampened cardiac function. Restoring LARP7 expression after myocardial infarction by either adeno-associated virus-mediated LARP7 expression or small molecule ATM inhibitor substantially improved the function of injured heart.

Conclusions: LARP7 is essential for mitochondrial biogenesis, energy production, and cardiac function by modulating SIRT1 homeostasis and activity. Reduction of LARP7 in diseased hearts owing to activation of the ATM pathway contributes to HF pathogenesis and restoring LARP7 in the injured heart confers myocardial protection. These results identify the ATM-LARP7-SIRT1 pathway as a target for therapeutic intervention in HF.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050812DOI Listing
May 2021

Benzo/Naphthodifuranone-Based Polymers: Effect of Perpendicular-Extended Main Chain π-Conjugation on Organic Field-Effect Transistor Performances.

Macromol Rapid Commun 2021 Apr 5;42(7):e2000703. Epub 2021 Feb 5.

Key Laboratory of Rubber-Plastics of Ministry of Education/Shandong Province (QUST), School of Polymer Science and Engineering, Qingdao University of Science and Technology, 53-Zhengzhou Road, Qingdao, 266042, P. R. China.

For polymer semiconductors, the backbone structure plays an essential role in determining their physicochemical properties and charge transport behaviors. In this work, two donor-acceptor-type polymers (P-BDF and P-NDF) based on benzodifuranone (BDF) and naphthodifunarone (NDF) as electron-deficient moieties and indaceno-dithiophene as electron-rich groups are designed, synthesized and, for the first time, applied in organic field-effect transistor. P-BDF and P-NDF differ from their backbone structures while P-BDF has a more planar backbone conformation due to its smaller conjugated core size and P-NDF features a perpendicular-extended main chain structure. As a result, P-BDF polymer exhibits bathochromic optical absorption, deeper molecular orbital energy levels, and more importantly, closer π-stacking and stronger aggregation in the solid state and thus affords a more promising hole mobility of up to 0.85 cm V s in OFET devices, while that of the P-NDF-based devices is only 0.55 cm V s . The results suggest the great potential of BDF/NDF-type chromophores in constructing novel organic semiconductors and also indicate that the main chain coplanarity of polymer semiconductors is more essential than the sole extension of π-conjugations (especially at the perpendicular direction of polymer main chains) for the design of high-performance OFET materials.
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http://dx.doi.org/10.1002/marc.202000703DOI Listing
April 2021

Endothelial Klf2-Foxp1-TGFβ signal mediates the inhibitory effects of simvastatin on maladaptive cardiac remodeling.

Theranostics 2021 1;11(4):1609-1625. Epub 2021 Jan 1.

Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Pathological cardiac fibrosis and hypertrophy are common features of left ventricular remodeling that often progress to heart failure (HF). Endothelial cells (ECs) are the most abundant non-myocyte cells in adult mouse heart. Simvastatin, a strong inducer of Krüppel-like Factor 2 (Klf2) in ECs, ameliorates pressure overload induced maladaptive cardiac remodeling and dysfunction. This study aims to explore the detailed molecular mechanisms of the anti-remodeling effects of simvastatin. RGD-magnetic-nanoparticles were used to endothelial specific delivery of siRNA and we found absence of simvastatin's protective effect on pressure overload induced maladaptive cardiac remodeling and dysfunction after inhibition of EC-Klf2. Mechanism studies showed that EC-Klf2 inhibition reversed the simvastatin-mediated reduction of fibroblast proliferation and myofibroblast formation, as well as cardiomyocyte size and cardiac hypertrophic genes, which suggested that EC-Klf2 might mediate the anti-fibrotic and anti-hypertrophy effects of simvastatin. Similar effects were observed after Klf2 inhibition in cultured ECs. Moreover, Klf2 regulated its direct target gene TGFβ1 in ECs and mediated the protective effects of simvastatin, and inhibition of EC-Klf2 increased the expression of EC-TGFβ1 leading to simvastatin losing its protective effects. Also, EC-Klf2 was found to regulate EC-Foxp1 and loss of EC-Foxp1 attenuated the protective effects of simvastatin similar to EC-Klf2 inhibition. We conclude that cardiac microvasculature ECs are important in the modulation of pressure overload induced maladaptive cardiac remodeling and dysfunction, and the endothelial Klf2-TGFβ1 or Klf2-Foxp1-TGFβ1 pathway mediates the preventive effects of simvastatin. This study demonstrates a novel mechanism of the non-cholesterol lowering effects of simvastatin for HF prevention.
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http://dx.doi.org/10.7150/thno.48153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778601PMC
August 2021

Dynamics of phosphorus fractions and potential bioavailability along soil profiles from seasonal-flooding wetlands in a Chinese estuary.

Environ Sci Pollut Res Int 2021 Feb 30;28(6):6549-6560. Epub 2020 Sep 30.

State Key Laboratory of Water Environment Simulation, School of Environment, Beijing Normal University, Beijing, 100875, China.

Soil phosphorus fractions in wetland ecosystems have received increasing attention due to its high eutrophication risks. Soil samples were collected to 40 cm depth in three sampling seasons to investigate the seasonal dynamics of organic and inorganic phosphorus fractions, bioavailability, and relationship between those and soil properties in a seasonal-flooding wetland in the Yellow River Estuary. The results showed that inorganic phosphorus (IP) and organic phosphorus (OP) contents exhibited much higher levels in the top 10 cm soils, and declined along soil profiles in spring. IP kept constant along soil profiles in fall, while OP decreased in summer and fall. They were greatly affected by water content (WC), pH, Cl/SO, soil organic matter (SOM), and electrical conductivity (EC). Middle labile organic phosphorus (MLOP) and non-labile organic phosphorus (NLOP) accounted for higher percentages of total OP in summer and fall respectively than labile organic phosphorus (LOP) in spring. MLOP and NLOP levels showed a decrease along soil profiles in spring and in spring/fall, respectively, while NLOP significantly increased with depth in summer. Ca-P was the dominant IP fraction in all soils in three sampling seasons, declined with depth in spring/fall and increased in summer. Comparatively, soluble/loosely-P(S/L-P) generally decreased with depth along soil profiles in three sampling seasons. And residual P (Res-P) kept little change with depth in spring. Fe/Al-P levels decreased firstly and then increased with depth in spring and summer. Available phosphorus and potential bioavailable phosphorus contents decreased with depth in spring and summer not in fall, and had a strong significant positive correlation with WC and SOM. Alkaline phosphatase not acid phosphatase was the key factor influencing soil MLOP levels. Generally, the fractions and bioavailability of phosphorus as well as phosphatase in this region were affected by soil depth, sampling seasons, and soil properties (e.g., WC, pH, Cl/SO, SOM, and EC).
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http://dx.doi.org/10.1007/s11356-020-10732-0DOI Listing
February 2021

Sequential Dual Attention Network for Rain Streak Removal in a Single Image.

IEEE Trans Image Process 2020 Sep 25;PP. Epub 2020 Sep 25.

Various weather conditions, such as rain, haze, or snow, can degrade visual quality in images/videos, which may significantly degrade the performance of related applications. In this paper, a novel framework based on sequential dual attention deep network is proposed for removing rain streaks (deraining) in a single image, called by SSDRNet (Sequential dual attentionbased Single image DeRaining deep Network). Since the inherent correlation among rain steaks within an image should be stronger than that between the rain streaks and the background (non-rain) pixels, a two-stage learning strategy is implemented to better capture the distribution of rain streaks within a rainy image. The two-stage deep neural network primarily involves three blocks: residual dense blocks (RDBs), sequential dual attention blocks (SDABs), and multi-scale feature aggregation modules (MAMs), which are all delicately and specifically designed for rain removal. The two-stage strategy successfully learns very fine details of the rain steaks of the image and then clearly removes them. Extensive experimental results have shown that the proposed deep framework achieves the best performance on qualitative and quantitative metrics compared with state-of-the-art methods. The corresponding code and the trained model of the proposed SSDRNet have been available online at https://github.com/fityanul/SDAN-for-Rain-Removal.
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http://dx.doi.org/10.1109/TIP.2020.3025402DOI Listing
September 2020

IL-12p40 gene expression in lung and hilar lymph nodes of MPS-resistant pigs.

Anim Sci J 2020 Jan;91(1):e13450

International Education and Research Center for Food and Agricultural Immunology (CFAI), Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.

Mycoplasma pneumonia of swine (MPS) is caused by Mycoplasma hyopneumoniae (M.hp) and is a common chronic respiratory disease of pigs. Recently, a genetically selected variant of the Landrace pig (Miyagino L2) has a lower incidence of pulmonary MPS lesions. We investigated the pathological and immunological characteristics of MPS resistance in these pigs (n = 24) by comparing with the normal landrace pig (control: n = 24). The pathological MPS lung lesion score in MPS-selected landrace pigs was significantly lower than in the control. The gene expression of interleukin (IL)-12p40, which acts as a chemoattractant and a component of the bioactive cytokines IL-12 and IL-23, was significantly higher at the hilar lymph nodes, lung, and spleen in MPS-selected landrace pigs than in control landrace pigs, and these were negatively correlated with the macroscopic MPS lung lesion score. In summary, we demonstrate that resistance against MPS in Miyagino L2 pigs is associated with IL-12p40 up-regulation, in comparison with normal landrace pigs without the MPS vaccine. In addition, a comparative study of macroscopic MPS lung lesions and IL-12p40 gene expression in lung and hilar lymph nodes may lead to beneficial selection traits for the genetic selection for MPS resistance in pigs.
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http://dx.doi.org/10.1111/asj.13450DOI Listing
January 2020

Synergistic effect of UV/chlorine in bacterial inactivation, resistance gene removal, and gene conjugative transfer blocking.

Water Res 2020 Oct 10;185:116290. Epub 2020 Aug 10.

Beijing Key Laboratory of Aqueous Typical Pollutants Control and Water Quality Safeguard, School of Civil Engineering, Beijing Jiaotong University, Beijing 100044, China.

Antibiotic resistant bacteria (ARB) and antibiotic resistance genes (ARGs) were investigated from effluent of two hospital and two municipal wastewater treatment plants (WWTPs) before and after disinfection. The results of network analysis showed that 8 genera were identified to be the main potential hosts of ARGs, including Mycobacterium, Ferruginibacter, Thermomonas, Morganella, Enterococcus, Bacteroides, Myroides and Romboutsia. The removal of ARGs and their possible bacterialhosts were synchronous and consistent by chlorine or ultraviolet (UV) disinfection in WWTPs. The mechanisms of ARB and ARGs removal, and conjugation transfer of RP4 plasmids by UV, chlorine and synergistic UV/chlorine disinfection was revealed. Compared to UV alone, ARB inactivation was improved 1.4 log and photoreactivation was overcomeeffectively by UV/chlorine combination (8 mJ/cm, chlorine 2 mg/L). However, ARGs degradation was more difficult than ARB inactivation. Until UV dosage enhanced to 320 mJ/cm, ARGs achieved 0.58-1.60 log removal. Meanwhile, when 2 mg/L of chlorine was combined with UV combination, ARGs removal enhanced 1-1.5 log. The synergistic effect of adding low-dose chlorine (1-2 mg/L) during UV radiation effectively improved ARB and ARGs removal simultaneously. The same synergistic effect also occurred in the horizontal gene transfer (HGT). Non-lethal dose chlorine (0.5 mg/L) increased the conjugation transfer frequency,which confirmed that the mRNA expression levels of type IV secretion system (T4SS) proteins vir4D, vir5B and vir10B were significantly enhanced. The risk of RP4 plasmid conjugation transfer was significantly reduced with UV/chlorine (UV ≥ 4 mJ/cm, chlorine ≥ 1 mg/L). These findings may serve as valuable implications for assessing and controlling the risk of ARGs transfer and propagation in the environment.
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http://dx.doi.org/10.1016/j.watres.2020.116290DOI Listing
October 2020

Risk assessment and investigation of landfill leachate as a source of emerging organic contaminants to the surrounding environment: a case study of the largest landfill in Jinan City, China.

Environ Sci Pollut Res Int 2021 Apr 17;28(15):18368-18381. Epub 2020 Jul 17.

Jinan Environmental Research Academy, Jinan, 250100, Shandong, People's Republic of China.

Emerging organic contaminants (EOCs) have been widely studied in landfill leachates but not in the surrounding environment of landfills. In this study, two sampling campaigns were conducted to determine 45 EOCs in landfill leachates and environmental samples near a landfill in East China. Our study focused on the seasonal occurrence and spatial distribution of the target EOCs, as well as their ecological risks. The results showed 13 out of 45 EOCs were detectable and achieved individual concentrations that ranged from 2.0 to 5080 ng/L in the landfill leachates. Most of the detected EOCs exhibited higher concentrations in the leachates collected in summer than in winter. Effective removal of the EOCs by a two-stage disc tube reverse osmosis (DTRO) system led to a significant reduction in their concentration levels (< LOQ ~ 49 ng/L) in treated leachates. Eight EOCs (< LOQ ~ 62.7 ng/L) were detected in the groundwater adjacent to the landfill and had a similar composition pattern to raw leachates. The contamination levels of the target EOCs in groundwater decreased with the distance of sampling sites from the landfill. In soil samples, the occurrence of target EOCs was not consistent with raw or treated landfill leachates. Spatially, no apparent difference in the EOC concentrations was observed in the soil nearby the landfill. Crop plants sorbed the EOCs contained in soil (< LOQ ~ 30.4 ng/L), but they were not able to bioconcentrate the contaminants in either roots or edible parts. Risk assessment suggested that the individual EOC likely posed medium to high risks to aquatic organisms in groundwater while negligible impacts to human health through consumption of vegetables. To the best of our knowledge, this is the first report on the contribution of landfill leachates to EOC contamination in both aquatic and soil environments in East China. Our findings emphasized the importance of investigating EOCs in landfill leachates and accumulative environmental risks of EOCs in the neighboring environment of landfills in China.
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http://dx.doi.org/10.1007/s11356-020-10093-8DOI Listing
April 2021

Interfacial Synthesis of a Monolayered Fluorescent Two-Dimensional Polymer through Dynamic Imine Chemistry.

ChemistryOpen 2020 03 24;9(3):381-385. Epub 2020 Mar 24.

College of Polymer Science and Engineering Qingdao University of Science and Technology Qingdao 266042 China.

A fluorescent monolayered two-dimensional polymer (2DP) containing both tetraphenylethylene (TPE) and imine linkages is synthesized at air-water interface using the Langmuir-Blodgett method. We designed TPE-based monomers with long distances between the TPE and the imine linkages to avoid the charge transfer and therefore keep the fluorescence. A monolayered 2DP provided with more than 104 μm in domain size and around 0.8 nm thickness was obtained through a successive Schiff base reaction at air-water interface. The nanostructures and fluorescent property of 2DP films were characterized by optical microscopy, SEM, TEM, AFM and fluorescence spectrum. Most importantly, the tip-enhanced Raman spectroscopy (TERS) was utilized here to confirm the success of the polycondensation of monolayered 2DP.
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http://dx.doi.org/10.1002/open.202000041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7092776PMC
March 2020

Vascular endothelial S1pr1 ameliorates adverse cardiac remodelling via stimulating reparative macrophage proliferation after myocardial infarction.

Cardiovasc Res 2021 01;117(2):585-599

Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, 150 Jimo Rd, Pudong New District, Shanghai 200120, China.

Aims: Endothelial cell (EC) homoeostasis plays an important role in normal physiological cardiac functions, and its dysfunction significantly influences pathological cardiac remodelling after myocardial infarction (MI). It has been shown that the sphingosine 1-phosphate receptor 1 (S1pr1) was highly expressed in ECs and played an important role in maintaining endothelial functions. We thus hypothesized that the endothelial S1pr1 might be involved in post-MI cardiac remodelling.

Methods And Results: Our study showed that the specific loss of endothelial S1pr1 exacerbated post-MI cardiac remodelling and worsened cardiac dysfunction. We found that the loss of endothelial S1pr1 significantly reduced Ly6clow macrophage accumulation, which is critical for the resolution of inflammation and cardiac healing following MI. The reduced reparative macrophages in post-MI myocardium contributed to the detrimental effects of endothelial S1pr1 deficiency on post-MI cardiac remodelling. Further investigations showed that the loss of endothelial S1pr1-reduced Ly6clow macrophage proliferation, while the pharmacological activation of S1pr1-enhanced Ly6clow macrophage proliferation, thereby ameliorated cardiac remodelling after MI. A mechanism study showed that S1P/S1pr1 activated the ERK signalling pathway and enhanced colony-stimulating factor 1 (CSF1) expression, which promoted Ly6clow macrophage proliferation in a cell-contact manner. The blockade of CSF1 signalling reversed the enhancing effect of S1pr1 activation on Ly6clow macrophage proliferation and worsened post-MI cardiac remodelling.

Conclusion: This study reveals that cardiac microvascular endothelium promotes reparative macrophage proliferation in injured hearts via the S1P/S1PR1/ERK/CSF1 pathway and thus ameliorates post-MI adverse cardiac remodelling.
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http://dx.doi.org/10.1093/cvr/cvaa046DOI Listing
January 2021

Endothelial S1pr1 regulates pressure overload-induced cardiac remodelling through AKT-eNOS pathway.

J Cell Mol Med 2020 01 19;24(2):2013-2026. Epub 2019 Dec 19.

Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Cardiac vascular microenvironment is crucial for cardiac remodelling during the process of heart failure. Sphingosine 1-phosphate (S1P) tightly regulates vascular homeostasis via its receptor, S1pr1. We therefore hypothesize that endothelial S1pr1 might be involved in pathological cardiac remodelling. In this study, heart failure was induced by transverse aortic constriction (TAC) operation. S1pr1 expression is significantly increased in microvascular endothelial cells (ECs) of post-TAC hearts. Endothelial-specific deletion of S1pr1 significantly aggravated cardiac dysfunction and deteriorated cardiac hypertrophy and fibrosis in myocardium. In vitro experiments demonstrated that S1P/S1pr1 praxis activated AKT/eNOS signalling pathway, leading to more production of nitric oxide (NO), which is an essential cardiac protective factor. Inhibition of AKT/eNOS pathway reversed the inhibitory effect of EC-S1pr1-overexpression on angiotensin II (AngII)-induced cardiomyocyte (CM) hypertrophy, as well as on TGF-β-mediated cardiac fibroblast proliferation and transformation towards myofibroblasts. Finally, pharmacological activation of S1pr1 ameliorated TAC-induced cardiac hypertrophy and fibrosis, leading to an improvement in cardiac function. Together, our results suggest that EC-S1pr1 might prevent the development of pressure overload-induced heart failure via AKT/eNOS pathway, and thus pharmacological activation of S1pr1 or EC-targeting S1pr1-AKT-eNOS pathway could provide a future novel therapy to improve cardiac function during heart failure development.
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http://dx.doi.org/10.1111/jcmm.14900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6991681PMC
January 2020

Endothelial Foxp1 Suppresses Atherosclerosis via Modulation of Nlrp3 Inflammasome Activation.

Circ Res 2019 08 18;125(6):590-605. Epub 2019 Jul 18.

From the Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine (T.Z., J.L., X.C., L.Z., H.S., Z.Y., Z.L., Y.Z.), Shanghai East Hospital, Tongji University School of Medicine, China.

Rationale: Endothelial dysfunction results in sustained and chronic vascular inflammation, which is central to atherosclerotic diseases. However, transcriptional regulation of vascular endothelial inflammation has not been well clarified.

Objective: This study aims to explore Foxp (forkhead box P) transcription factor 1 in regulation of endothelial homeostasis, atherogenesis, and its mechanisms.

Methods And Results: To assess the importance of Foxp1 in atherosclerosis, Foxp1 expression was analyzed in human coronary artery and mouse artery, and we observed significant downregulation of Foxp1 in atherosclerotic and atherosusceptible endothelium. Endothelial-specific Foxp1 knockout mice (Foxp1) were bred onto Apoe mice to generate endothelial Foxp1-deletion hyperlipidemic model Foxp1;Apoe, which displayed significant increases in atherosclerotic lesion formation in aortas and aortic roots with enhanced monocyte adhesion, migration, and infiltration into the vascular wall and formation of inflammatory lipid-laden macrophages. In contrast, endothelial-specific Foxp1 overexpression mice Foxp1;Apoe exhibited reduced atherosclerotic lesion formation with less monocyte infiltration. Foxp1 was further identified as a gatekeeper of vessel inflammation by direct regulation of endothelial inflammasome components, including Nlrp3 (NLR [nucleotide-binding and leucine-rich repeat immune receptors] family pyrin domain containing 3), caspase-1, and IL (interleukin)-1β. Moreover, endothelial Foxp1 was found to be regulated by Klf2 (Kruppel-like factor 2). Oscillatory shear stress downregulated Foxp1 expression via repressing Klf2 expression in endothelium, and, therefore, promoted endothelial inflammasome activation, leading to atherosclerotic lesion formation. Simvastatin upregulated the reduced expression of Klf2 and Foxp1 in atherosusceptible vascular endothelium and alleviated vascular inflammation contributing to its inhibitory effect in atherosclerosis.

Conclusions: These data are the first in vivo experimental validation of an atheroprotective role of endothelial Klf2 and Foxp1, which reveals a Klf2-Foxp1 transcriptional network in endothelial cells as a novel regulator of endothelial inflammasome activation for atherogenesis, therefore, provides opportunities for therapeutic intervention of atherosclerotic diseases and uncovers a novel atheroprotective mechanism for simvastatin.
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http://dx.doi.org/10.1161/CIRCRESAHA.118.314402DOI Listing
August 2019

Endothelial Forkhead Box Transcription Factor P1 Regulates Pathological Cardiac Remodeling Through Transforming Growth Factor-β1-Endothelin-1 Signal Pathway.

Circulation 2019 08 10;140(8):665-680. Epub 2019 Jun 10.

Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine (J.L., T.Z., X.C., Z.Y., L.Z., Z.L., Y.Z.), Tongji University School of Medicine, China.

Background: Pathological cardiac fibrosis and hypertrophy, the common features of left ventricular remodeling, often progress to heart failure. Forkhead box transcription factor P1 (Foxp1) in endothelial cells (ECs) has been shown to play an important role in heart development. However, the effect of EC-Foxp1 on pathological cardiac remodeling has not been well clarified. This study aims to determine the role of EC-Foxp1 in pathological cardiac remodeling and the underlying mechanisms.

Methods: Foxp1 EC-specific loss-of-function and gain-of-function mice were generated, and an angiotensin II infusion or a transverse aortic constriction operation mouse model was used to study the cardiac remodeling mechanisms. Foxp1 downstream target gene transforming growth factor-β1 (TGF-β1) was confirmed by chromatin immunoprecipitation and luciferase assays. Finally, the effects of TGF-β1 blockade on EC-Foxp1 deletion-mediated profibrotic and prohypertrophic phenotypic changes were further confirmed by pharmacological inhibition, more specifically by RGD-peptide magnetic nanoparticle target delivery of TGF-β1-siRNA to ECs.

Results: Foxp1 expression is significantly downregulated in cardiac ECs during angiotensin II-induced cardiac remodeling. EC-Foxp1 deletion results in severe cardiac remodeling, including more cardiac fibrosis with myofibroblast formation and extracellular matrix protein production, as well as decompensated cardiac hypertrophy and further exacerbation of cardiac dysfunction on angiotensin II infusion or transverse aortic constriction operation. In contrast, EC-Foxp1 gain of function protects against pathological cardiac remodeling and improves cardiac dysfunction. TGF-β1 signals are identified as Foxp1 direct target genes, and EC-Foxp1 deletion upregulates TGF-β1 signals to promote myofibroblast formation through fibroblast proliferation and transformation, resulting in severe cardiac fibrosis. Moreover, EC-Foxp1 deletion enhances TGF-β1-promoted endothelin-1 expression, which significantly increases cardiomyocyte size and reactivates cardiac fetal genes, leading to pathological cardiac hypertrophy. Correspondingly, these EC-Foxp1 deletion-mediated profibrotic and prohypertrophic phenotypic changes and cardiac dysfunction are normalized by the blockade of TGF-β1 signals through pharmacological inhibition and RGD-peptide magnetic nanoparticle target delivery of TGF-β1-siRNA to ECs.

Conclusions: EC-Foxp1 regulates the TGF-β1-endothelin-1 pathway to control pathological cardiac fibrosis and hypertrophy, resulting in cardiac dysfunction. Therefore, targeting the EC-Foxp1-TGF-β1-endothelin-1 pathway might provide a future novel therapy for heart failure.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.039767DOI Listing
August 2019

Response to Comment on "Controlling for Ascertainment Bias May Introduce Control Group Bias in Prospective Nonrandomized Trials".

Ann Surg 2019 08;270(2):e55

Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, China Department of Epidemiology, Peking University Health Science Center, Beijing, China Beijing Medical Development Clinical Research Institute, Beijing, China Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China Key Laboratory of Colorectal Cancer Diagnosis and Treatment Research, Beijing, China Department of Gastrointestinal Surgery, Peking University People's Hospital, Beijing, China Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing, China.

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http://dx.doi.org/10.1097/SLA.0000000000003152DOI Listing
August 2019

Cell-Specific Effects of GATA (GATA Zinc Finger Transcription Factor Family)-6 in Vascular Smooth Muscle and Endothelial Cells on Vascular Injury Neointimal Formation.

Arterioscler Thromb Vasc Biol 2019 05;39(5):888-901

From the Key Laboratory of Arrhythmias of the Ministry of Education of China, Research Center for Translational Medicine (T.Z., J.L., X.C., Y.K., Y.W., Z.Y., L.Z., Z.L., Y.Z.), Shanghai East Hospital, Tongji University School of Medicine, China.

Objective- Transcription factor GATA (GATA zinc finger transcription factor family)-6 is highly expressed in vessels and rapidly downregulated in balloon-injured carotid arteries and viral delivery of GATA-6 to the vessels limited the neointimal formation, however, little is known about its cell-specific regulation of in vivo vascular smooth muscle cell (VSMC) phenotypic state contributing to neointimal formation. This study aims to determine the role of vascular cell-specific GATA-6 in ligation- or injury-induced neointimal hyperplasia in vivo. Approach and Results- Endothelial cell and VSMC-specific GATA-6 deletion mice are generated, and the results indicate that endothelial cell-specific GATA-6 deletion mice exhibit significant decrease of VSMC proliferation and attenuation of neointimal formation after artery ligation and injury compared with the wild-type littermate control mice. PDGF (platelet-derived growth factor)-B is identified as a direct target gene, and endothelial cell-GATA-6-PDGF-B pathway regulates VSMC proliferation and migration in a paracrine manner which controls the neointimal formation. In contrast, VSMC-specific GATA-6 deletion promotes injury-induced VSMC transformation from contractile to proliferative synthetic phenotype leading to increased neointimal formation. CCN (cysteine-rich 61/connective tissue growth factor/nephroblastoma overexpressed family)-5 is identified as a novel target gene, and VSMC-specific CCN-5 overexpression in mice reverses the VSMC-GATA-6 deletion-mediated increased cell proliferation and migration and finally attenuates the neointimal formation. Conclusions- This study gives us a direct in vivo evidence of GATA-6 cell lineage-specific regulation of PDGF-B and CCN-5 on VSMC phenotypic state, proliferation and migration contributing to neointimal formation, which advances our understanding of in vivo neointimal hyperplasia, meanwhile also provides opportunities for future therapeutic interventions.
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http://dx.doi.org/10.1161/ATVBAHA.118.312263DOI Listing
May 2019

Theoretical investigation on atmospheric oxidation of fluorene initiated by OH radical.

Sci Total Environ 2019 Jun 27;669:920-929. Epub 2019 Feb 27.

Jinan Environmental Research Academy, Jinan 250102, PR China.

Atmospheric oxidation of fluorene and its derivatives initiated by OH radicals was investigated theoretically with quantum chemical calculation methods [M06-2X/6-311++G(3df,2p)//M06-2X/6-311+G(d,p)]. It revealed that the OH addition pathways form hydroxyfluorene and ring-opening product dialdehyde while the H abstraction pathways lead to the formation of 9-fluorenone. Subsequent oxidation of 9-fluorenone has considerable potential to form dibenzo-p-dioxin and nitrofluorenone according to the present calculation results. The atmospheric lifetime of fluorene relative to the reactions with OH radicals is deduced to be 12.51 h based on the calculated overall rate constant (2.29 × 10 cm molecule s) at 298 K and 1 atm. The oxidation products of fluorene in the atmosphere are generally more toxic and persistent. This work provides a comprehensive explanation for atmospheric oxidation processes of fluorene and facilitates clarifying its environmental risks.
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http://dx.doi.org/10.1016/j.scitotenv.2019.02.400DOI Listing
June 2019

Amendment of municipal sewage sludge with lime and mussel shell: Effects on fate of organic matter and pharmaceutically active compounds.

Waste Manag 2019 Feb 4;85:272-282. Epub 2019 Jan 4.

Institute of Soil, Jinan Environmental Research Academy, Jinan 250102, PR China.

The deterioration in its strength from long-term degradation of organic matter and release of pharmaceutically active compounds (PhACs) have caused adverse environmental effects in municipal sewage sludge (MSS) landfill. Lime and a mixture of lime and mussel shell were employed as potential stabilization agents for MSS in this work. Their efficacy was assessed by investigating the effects on transformation of organic matter, as well as the occurrence and fate of four PhACs (fluoxetine, gemfibrozil, triclosan and carbamazepine) over 42 days. The addition of the selected agents: (i) prevented the microbial degradation of organic matter; (ii) modified the predominant functional groups of amide groups (amide I and II) and polysaccharides to deprotonated carboxylic groups and destruction of amide groups; and (iii) shifted the abundance of organic constituents from microbial by-products to humic acid-like organics with conformational changes. The measurement method provided reliable and precise results for determining PhAC concentrations in MSS with and without amendment, although matrix effects and process effects were found to affect measurement sensitivity. Available fractions of the PhACs increased in MSS with lime addition, but decreased in the presence of the mixture of lime and mussel shell due to the strong adsorption effects of the shells. The mixture of lime and mussel shell would be recommended for stabilizing MSS prior to being landfilled. However, longer term and larger scale investigation may be needed to better evaluate the applicability of lime and mussel shell for reducing the hazards and facilitating the management of MSS.
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http://dx.doi.org/10.1016/j.wasman.2018.12.035DOI Listing
February 2019

Mechanistic studies on the dibenzofuran and dibenzo‑p‑dioxin formation reactions from anthracene.

Sci Total Environ 2019 Apr 28;662:41-47. Epub 2018 Dec 28.

Environment Research Institute, Shandong University, Jinan 250100, PR China.

Polychlorinated dibenzo‑p‑dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) are highly toxic, carcinogenic and mutagenic to humans. As precursors of PCDD/Fs, dibenzofuran (DF) and dibenzo‑p‑dioxin (DD) have received considerable public and scientific attention. To reduce the emission of PCDD/Fs, it is critical to explore the formation mechanisms of DF and DD. The present study delineated the DF and DD formation mechanisms from anthracene partial oxidation with the aid of high-accuracy quantum chemistry calculations. The rate constants of crucial elementary steps were obtained utilizing canonical variational transition-state (CVT) theory with the small curvature tunneling (SCT) correction. The results indicate that anthracene could be important precursor of DF and DD, because of the potential barriers for all the major elementary reactions are lower than 33.54kcalmol. This work also reveals that water molecule plays an important catalytic effect during the formation of both DF and DD by lowering the barriers of about 27.24kcalmol. For the water-assisted formation pathway, DF is the dominate product of anthracene partial oxidation with the highest barrier of 30.45kcalmol. For the non-water-assisted formation pathway, DD is the dominate product with the highest barrier of 33.54kcalmol.
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http://dx.doi.org/10.1016/j.scitotenv.2018.12.408DOI Listing
April 2019
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