Publications by authors named "Ling Tao"

366 Publications

Mercury and selenium in squids from the Pacific Ocean and Indian Ocean: The distribution and human health implications.

Mar Pollut Bull 2021 Sep 16;173(Pt A):112926. Epub 2021 Sep 16.

College of Marine Science, Shanghai Ocean University, Shanghai 201306, China.

Squids are globally distributed. Hg-contaminated squids may have high risks on humans. With abundant Se (antagonistic effect on Hg), the risks can be reduced. We collected squids around the world (Northwest Pacific Ocean, Southeast Pacific Ocean and Indian Ocean). Concentrations of Hg and Se were region-based and tissue-based. The higher content of Se were, the lower relative Hg levels were. The correlation between Se:Hg and Se was the strongest in the digestive gland. The values of Se:Hg and THQ all confirm that the health risk was lower in samples with higher concentrations of Se. Despite the risk assessment by Se:Hg, BRV and THQ analysis showed no risk when consumed in moderation, the maximum daily intake is provided based on Monte Carlo simulation. In future, when evaluating the risks cause by Hg exposure and providing the recommended daily amount, it may need to concurrent consideration of Se levels.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112926DOI Listing
September 2021

Stress Assessment of Vestibular Endurance Training for Civil Aviation Flight Students Based on EEG.

Front Hum Neurosci 2021 19;15:582636. Epub 2021 Aug 19.

Department of Biomedical Engineering, Nanjing University of Aeronautics and Astronautics, Nanjing, China.

The main goal of this study is to clarify the electroencephalogram (EEG) characteristics of the stress response caused by vestibular endurance training under real conditions. Ten pilot trainees received a series of acute anti-vertigo training stimulations on the rotary ladder while recording electroencephalographic data (64 electrodes). Afterward, the anti-vertigo ability of the subject was tested for the best performance after 1 month of training and verified whether it is related to the EEG signals we collected before. (1) The absolute power of α waves in the C3 and C4 regions is the same as the difference between 1 min before and 2 min after stimulation, and their activity is enhanced by stimulation. Otherwise, the activation of the C3 region after 5 min of stimulation is still significantly changed. (2) Through Spearman's correlation analysis, we found that the α waves in the C3 and C4 the greater the power change, the better the performance of the subject in the proficient stage. C3 and C4 areas are specific brain regions of the stress response of anti-vertigo endurance training, and the absolute power of the α wave can be used as a parameter for identifying the degree of motion sickness (MS). The absolute power changes of α waves in the C3 and C4 areas are positively correlated with their anti-vertigo potential. Increasing the absolute power of α wave in the C3 and C4 is a manifestation of MS stress adaptability.
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http://dx.doi.org/10.3389/fnhum.2021.582636DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8417248PMC
August 2021

Degradation of WTAP blocks antiviral responses by reducing the m A levels of IRF3 and IFNAR1 mRNA.

EMBO Rep 2021 Sep 1:e52101. Epub 2021 Sep 1.

Guangdong Province Key Laboratory of Pharmaceutical Functional Genes, MOE Key Laboratory of Gene Function and Regulation, State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-Sen University, Guangzhou, China.

N -methyladenosine (m A) is a chemical modification present in multiple RNA species and is most abundant in mRNAs. Studies on m A reveal its comprehensive roles in almost every aspect of mRNA metabolism, as well as in a variety of physiological processes. Although some recent discoveries indicate that m A can affect the life cycles of numerous viruses as well as the cellular antiviral immune response, the roles of m A modification in type I interferon (IFN-I) signaling are still largely unknown. Here, we reveal that WT1-associated protein (WTAP), one of the m A "writers", is degraded via the ubiquitination-proteasome pathway upon activation of IFN-I signaling. With the degradation of WTAP, the m A levels of IFN-regulatory factor 3 (IRF3) and interferon alpha/beta receptor subunit 1 (IFNAR1) mRNAs are reduced, leading to translational suppression of IRF3 and instability of IFNAR1 mRNA. Thus, the WTAP-IRF3/IFNAR1 axis may serve as negative feedback pathway to fine-tune the activation of IFN-I signaling, which highlights the roles of m A in the antiviral response by dictating the fate of mRNAs associated with IFN-I signaling.
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http://dx.doi.org/10.15252/embr.202052101DOI Listing
September 2021

Coxsackievirus A2 Leads to Heart Injury in a Neonatal Mouse Model.

Viruses 2021 Aug 11;13(8). Epub 2021 Aug 11.

Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.

Coxsackievirus A2 (CVA2) has emerged as an active pathogen that has been implicated in hand, foot, and mouth disease (HFMD) and herpangina outbreaks worldwide. It has been reported that severe cases with CVA2 infection develop into heart injury, which may be one of the causes of death. However, the mechanisms of CVA2-induced heart injury have not been well understood. In this study, we used a neonatal mouse model of CVA2 to investigate the possible mechanisms of heart injury. We detected CVA2 replication and apoptosis in heart tissues from infected mice. The activity of total aspartate transaminase (AST) and lactate dehydrogenase (LDH) was notably increased in heart tissues from infected mice. CVA2 infection also led to the disruption of cell-matrix interactions in heart tissues, including the increases of matrix metalloproteinase (MMP)3, MMP8, MMP9, connective tissue growth factor (CTGF) and tissue inhibitors of metalloproteinases (TIMP)4. Infiltrating leukocytes (CD45 and CD11b cells) were observed in heart tissues of infected mice. Correspondingly, the expression levels of inflammatory cytokines in tissue lysates of hearts, including tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), IL6 and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in CVA2 infected mice. Inflammatory signal pathways in heart tissues, including phosphatidylinositol 3-kinase (PI3K)-AKT, mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB), were also activated after infection. In summary, CVA2 infection leads to heart injury in a neonatal mouse model, which might be related to viral replication, increased expression levels of MMP-related enzymes and excessive inflammatory responses.
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http://dx.doi.org/10.3390/v13081588DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402683PMC
August 2021

Impact of established cardiovascular disease on 10-year death after coronary revascularization for complex coronary artery disease.

Clin Res Cardiol 2021 Aug 25. Epub 2021 Aug 25.

Department of Cardiology, National University of Ireland, Galway (NUIG), P.O. University Road, Galway, H91 TK33, Ireland.

Aims: To investigate the impact of established cardiovascular disease (CVD) on 10-year all-cause death following coronary revascularization in patients with complex coronary artery disease (CAD).

Methods: The SYNTAXES study assessed vital status out to 10 years of patients with complex CAD enrolled in the SYNTAX trial. The relative efficacy of PCI versus CABG in terms of 10-year all-cause death was assessed according to co-existing CVD.

Results: Established CVD status was recorded in 1771 (98.3%) patients, of whom 827 (46.7%) had established CVD. Compared to those without CVD, patients with CVD had a significantly higher risk of 10-year all-cause death (31.4% vs. 21.7%; adjusted HR: 1.40; 95% CI 1.08-1.80, p = 0.010). In patients with CVD, PCI had a non-significant numerically higher risk of 10-year all-cause death compared with CABG (35.9% vs. 27.2%; adjusted HR: 1.14; 95% CI 0.83-1.58, p = 0.412). The relative treatment effects of PCI versus CABG on 10-year all-cause death in patients with complex CAD were similar irrespective of the presence of CVD (p = 0.986). Only those patients with CVD in ≥ 2 territories had a higher risk of 10-year all-cause death (adjusted HR: 2.99, 95% CI 2.11-4.23, p < 0.001) compared to those without CVD.

Conclusions: The presence of CVD involving more than one territory was associated with a significantly increased risk of 10-year all-cause death, which was non-significantly higher in complex CAD patients treated with PCI compared with CABG. Acceptable long-term outcomes were observed, suggesting that patients with established CVD should not be precluded from undergoing invasive angiography or revascularization.

Trial Registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.
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http://dx.doi.org/10.1007/s00392-021-01922-yDOI Listing
August 2021

Revascularization by percutaneous coronary intervention in a case of left main coronary artery atresia.

Catheter Cardiovasc Interv 2021 Aug 19. Epub 2021 Aug 19.

Department of Cardiology, Xijing Hospital, Air Force Medical University, China.

Left main coronary artery atresia (LMCAA) is a rare congenital anomaly of the coronary artery that may have an unfavorable prognosis if left untreated. Surgical revascularization by either coronary artery bypass grafting or coronary reconstruction osteoplasty is unanimously recognized as the treatment of choice for this condition. Here, we first report a case of LMCAA treated with revascularization by percutaneous coronary intervention (PCI) through a retrograde approach. Intravascular ultrasound revealed an unusual coronary structure for the left main artery. PCI appears to be a feasible and effective alternative to surgery for the treatment of LMCAA, particularly if a minimally invasive method is desired.
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http://dx.doi.org/10.1002/ccd.29931DOI Listing
August 2021

Quantitative Angiographic Assessment of Aortic Regurgitation After Transcatheter Implantation of the Venus A-valve: Comparison with Other Self-Expanding Valves and Impact of a Learning Curve in a Single Chinese Center.

Glob Heart 2021 4;16(1):54. Epub 2021 Aug 4.

Department of Cardiology, National University of Ireland, Galway (NUIG), Galway and CORRIB Research Center for Advanced Imaging and Core laboratory, IE.

Objectives: We aimed to compare the quantitative angiographic aortic regurgitation (AR) into the left ventricular out flow tract (LVOT-AR) of five different types of transcatheter self-expanding valves and to investigate the impact of the learning curve on post-TAVR AR.

Background: Quantitative video densitometric aortography is an objective, accurate, and reproducible tool for assessment of AR following TAVR.

Methods And Results: This retrospective academic core-lab analysis, analyzed 1150 consecutive cine aortograms performed immediately post-TAVR. Quantitative angiographic AR of post-procedural aortography in 181 consecutive patients, who underwent TAVR with the Venus A-valve in a single Chinese center, were compared to the results of Evolut Pro, Evolut R, CoreValve, (Medtronic, Dublin, Ireland) and Acurate Neo (Boston Scientific, Massachusetts, US) transcatheter heart valves (THVs), from a previously published pooled database. Among the 181 aortograms of patients treated with the Venus A-Valve, 113 (62.4%) were analyzable for quantitative assessment of AR. The mean LVOT-AR was 8.9% ± 10.0% with 14.2% of patients having moderate or severe AR in the Venus A-valve group. No significant difference in mean LVOT-AR was observed between Evolut Pro, Evolut R, Acurate Neo, and Venus A-valve. The incidence of LVOT-AR >17%, which correlates with echocardiographic derived ≥ moderate AR, with the Evolut Pro was lower than with the Venus A-valve (5.3% vs. 14.2%, p = 0.034), but was not different from the Evolut R (5.3% vs. 8.8%, p = 0.612), or the Acurate Neo (5.3% vs. 11.3% p = 0.16) systems. A landmark analysis after recruitment of the first half of patients treated with the Venus A valve (N = 56), showed a significantly lower mean LVOT-AR in the second half of the series (11.3% ± 11.9% vs. 6.5% ± 7.1%, p = 0.011). The incidence of LVOT-AR >17% in the latest 57 cases was also numerically lower (7.0% vs. 21.4%, p = 0.857) and compared favorably with the best in class of the self-expanding valves.

Conclusion: The Venus A-valve has comparable mean LVOT-AR to other self-expanding valves but has a higher rate of moderate or severe AR than the Evolut Pro THV. However, after completion of a learning phase, results improved and compared favorably with the best in class of the commercially available self-expanding valves. These findings should be confirmed in prospective randomized comparisons of AR between different THVs.
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http://dx.doi.org/10.5334/gh.1046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344958PMC
August 2021

Prediction of Rivaroxaban-Rifampin Interaction After Major Orthopedic Surgery: Physiologically Based Pharmacokinetic Modeling and Simulation.

Front Pharmacol 2021 23;12:706781. Epub 2021 Jul 23.

Department of Sports Medicine and Adult Reconstructive Surgery, Drum Tower Hospital Affiliated to Medical School of Nanjing University, Nanjing, China.

Rivaroxaban is commonly used for the prophylaxis of venous thromboembolism (VTE) for patients undergoing major orthopedic surgery. Rivaroxaban is primarily eliminated by hepatic CYP450 metabolism and renal excretion. Rifampin is a commonly used antibiotic for prosthetic joint infections (PJI) and a potent inducer of CYP450 enzymes. Clinical data about drug-drug interactions of rivaroxaban and rifampin are limited. The present study is to describe DDI of rivaroxaban and rifampin in several prosthetic joint infections patients undergoing major orthopedic surgery. We retrospectively identified six patients concomitantly administered with rivaroxaban and rifampin between 2019 and 2020. Plasma samples of these patients with accurate sampling time were chosen from the biobank and plasma levels of rivaroxaban were measured at each time point. A physiologically based pharmacokinetic model for the rivaroxaban-rifampin interaction was developed to predict the optimal dosing regimen of rivaroxaban in the case of co-medication with rifampin. The model was validated by the observed plasma concentration of rivaroxaban from the above patients. From this model, it could be simulated that when rifampin starts or stops, gradually changing rivaroxaban dose during the first few days would elevate the efficacy and safety of rivaroxaban.
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http://dx.doi.org/10.3389/fphar.2021.706781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342882PMC
July 2021

Effects of Tranexamic Acid on Hemorrhage Control and Deep Venous Thrombosis Rate After Total Knee Arthroplasty: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Front Pharmacol 2021 21;12:639694. Epub 2021 Jul 21.

Department of Pharmacy, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, China.

Total knee arthroplasty (TKA) surgery has a lot of complications, especially hemorrhage, which can be controlled tranexamic acid (TXA). The guidelines endorse the integration of TXA interventions in the management of TKA-induced complications. However, uncertainty surrounds the effects of different TXA therapies. This frequentist model network meta-analysis (NMA) aims to compare hemorrhage control and deep venous thrombosis (DVT) rate of different TXA therapies in TKA. Articles were searched with the PubMed, Embase, Cochrane Library, and Web of Science from 1966 to October 2020. Randomized controlled trials (RCTs) comparing different TXA therapies, or with placebo in patients with TKA were included. Two investigators independently conducted article retrievals and data collection. The outcome was total blood loss and DVT rate. Effect size measures were mean differences (MDs), or odds ratios (ORs) with 95% confidence intervals (CIs). We conducted a random-effects NMA using a frequentist approach to estimate relative effects for all comparisons and rank treatments according to the mean rank and surface under the cumulative ranking curve values. All analyses were performed in Stata software or R software. The study protocol was registered with PROSPERO, number CRD42020202404. We identified 1 754 citations and included 81 studies with data for 9 987 patients with TKA. Overall, all TXA therapies were superior to placebo for total blood loss in TKA. Of all TXA therapies, M therapy (IV/IV infusion + oral TXA > 3g) was most effective for total blood loss (MD=-688.48, -1084.04--328.93), followed by F therapy (IV TXA ≥ 15 mg/kg or 1 g three times). TXA therapies in this study are not associated with the increase of DVT risk. TXA therapies in this study are effective and safe for the treatment of TKA-induced complications. M therapy (IV/IV infusion + oral TXA > 3 g) may be the most effective TXA therapy for hemorrhage control. TXA therapies in this study do not increase DVT risk. Considering hemorrhage control and DVT rate simultaneously, F therapy (IV TXA ≥ 15 mg/kg or 1 g three times) may be suggested to apply for TKA, and this study may provide a crucial clue to future TXA use.
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http://dx.doi.org/10.3389/fphar.2021.639694DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8335562PMC
July 2021

CHAF1A Blocks Neuronal Differentiation and Promotes Neuroblastoma Oncogenesis via Metabolic Reprogramming.

Adv Sci (Weinh) 2021 Aug 8:e2005047. Epub 2021 Aug 8.

Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, 77030, USA.

Neuroblastoma (NB) arises from oncogenic disruption of neural crest (NC) differentiation. Treatment with retinoic acid (RA) to induce differentiation has improved survival in some NB patients, but not all patients respond, and most NBs eventually develop resistance to RA. Loss of the chromatin modifier chromatin assembly factor 1 subunit p150 (CHAF1A) promotes NB cell differentiation; however, the mechanism by which CHAF1A drives NB oncogenesis has remained unexplored. This study shows that CHAF1A gain-of-function supports cell malignancy, blocks neuronal differentiation in three models (zebrafish NC, human NC, and human NB), and promotes NB oncogenesis. Mechanistically, CHAF1A upregulates polyamine metabolism, which blocks neuronal differentiation and promotes cell cycle progression. Targeting polyamine synthesis promotes NB differentiation and enhances the anti-tumor activity of RA. The authors' results provide insight into the mechanisms that drive NB oncogenesis and suggest a rapidly translatable therapeutic approach (DFMO plus RA) to enhance the clinical efficacy of differentiation therapy in NB patients.
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http://dx.doi.org/10.1002/advs.202005047DOI Listing
August 2021

Environmental profile, distributions and potential sources of halogenated polycyclic aromatic hydrocarbons.

J Hazard Mater 2021 10 21;419:126164. Epub 2021 May 21.

College of Marine Ecology and Environment, Shanghai Ocean University, Shanghai 201306, China. Electronic address:

Halogenated polycyclic aromatic hydrocarbons (HPAHs) are high lipophilic and degradation-resistant, which have been detected in the air, water, sediment and biota. HPAHs tend to have strong adverse effects on animals and humans. Although we have realized HPAHs are emerging contaminants which needs to be paid attention, there is still a lack of their individual commercial standards. This makes it difficult for understanding HPAHs comprehensively. This review is devoted to collect all the results have reported, and give a systemic look of their global distributions, influence factors and sources. Compared with air, studies on other environmental matrices (water and sediment) are more limited. The researches on organisms are fewest. Comparing the studied congeners, there are more studies on ClPAHs than BrPAHs. Human activities contribute mostly to their occurrence. Further, we then also introduce the toxicity and analytical methods to better understand HPAHs. The future research directions are also provided. Through this review, we can conclude there is an urgent need to develop analysis methods and ecologic risk assessment for better exploring HPAHs. Effective methods should be done to control HPAHs. Therefore, this review can provide a good basis for researchers to understand and control global pollution.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126164DOI Listing
October 2021

FNDC5/Irisin attenuates diabetic cardiomyopathy in a type 2 diabetes mouse model by activation of integrin αV/β5-AKT signaling and reduction of oxidative/nitrosative stress.

J Mol Cell Cardiol 2021 Jul 3;160:27-41. Epub 2021 Jul 3.

Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China. Electronic address:

Irisin, the cleaved form of the fibronectin type III domain containing 5 (FNDC5) protein, is involved in metabolism and inflammation. Recent findings indicated that irisin participated in cardiovascular physiology and pathology. In this study, we investigated the effects of FNDC5/irisin on diabetic cardiomyopathy (DCM) in type 2 diabetic db/db mice. Downregulation of myocardial FNDC5/irisin protein expression and plasma irisin levels was observed in db/db mice compared to db/+ controls. Moreover, echocardiography revealed that db/db mice exhibited normal cardiac systolic function and impaired diastolic function. Adverse structural remodeling, including cardiomyocyte apoptosis, myocardial fibrosis, and cardiac hypertrophy were observed in the hearts of db/db mice. Sixteen-week-old db/db mice were intramyocardially injected with adenovirus encoding FNDC5 or treated with recombinant human irisin via a peritoneal implant osmotic pump for 4 weeks. Both overexpression of myocardial FNDC5 and exogenous irisin administration attenuated diastolic dysfunction and cardiac structural remodeling in db/db mice. Results from in vitro studies revealed that FNDC5/irisin protein expression was decreased in high glucose (HG)/high fat (HF)-treated cardiomyocytes. Increased levels of inducible nitric oxide synthase (iNOS), NADPH oxidase 2 (NOX2), 3-nitrotyrosine (3-NT), reactive oxygen species (ROS), and peroxynitrite (ONOO) in HG/HF-treated H9C2 cells provided evidence of oxidative/nitrosative stress, which was alleviated by treatment with FNDC5/irisin. Moreover, the mitochondria membrane potential (ΔΨm) was decreased and cytochrome C was released from mitochondria with increased levels of cleaved caspase-3 in HG/HF-treated H9C2 cells, indicating the presence of mitochondria-dependent apoptosis, which was partially reversed by FNDC5/irisin treatment. Mechanistic studies showed that activation of integrin αVβ5-AKT signaling and attenuation of oxidative/nitrosative stress were responsible for the cardioprotective effects of FNDC5/irisin. Therefore, FNDC5/irisin mediates cardioprotection in DCM by inhibiting myocardial apoptosis, myocardial fibrosis, and cardiac hypertrophy. These findings implicate that FNDC5/irisin as a potential therapeutic intervention for DCM, especially in type 2 diabetes mellitus (T2DM).
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http://dx.doi.org/10.1016/j.yjmcc.2021.06.013DOI Listing
July 2021

Restoration of the molecular clock is tumor suppressive in neuroblastoma.

Nat Commun 2021 06 28;12(1):4006. Epub 2021 Jun 28.

Department of Pediatrics, Section of Hematology-Oncology, Texas Children's Cancer and Hematology Centers, Baylor College of Medicine, Houston, TX, USA.

MYCN activation is a hallmark of advanced neuroblastoma (NB) and a known master regulator of metabolic reprogramming, favoring NB adaptation to its microenvironment. We found that the expression of the main regulators of the molecular clock loops is profoundly disrupted in MYCN-amplified NB patients, and this disruption independently predicts poor clinical outcome. MYCN induces the expression of clock repressors and downregulates the one of clock activators by directly binding to their promoters. Ultimately, MYCN attenuates the molecular clock by suppressing BMAL1 expression and oscillation, thereby promoting cell survival. Reestablishment of the activity of the clock activator RORα via its genetic overexpression and its stimulation through the agonist SR1078, restores BMAL1 expression and oscillation, effectively blocks MYCN-mediated tumor growth and de novo lipogenesis, and sensitizes NB tumors to conventional chemotherapy. In conclusion, reactivation of RORα could serve as a therapeutic strategy for MYCN-amplified NBs by blocking the dysregulation of molecular clock and cell metabolism mediated by MYCN.
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http://dx.doi.org/10.1038/s41467-021-24196-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238982PMC
June 2021

Neonatal Murine Model of Coxsackievirus A2 Infection for the Evaluation of Antiviral Therapeutics and Vaccination.

Front Microbiol 2021 28;12:658093. Epub 2021 May 28.

Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou, China.

Coxsackievirus (CV) A2 has emerged as an important etiological agent in the pathogen spectrum of hand, foot, and mouth disease (HFMD). The symptoms of CVA2 infections are generally mild, but worsen rapidly in some people, posing a serious threat to children's health. However, compared with enterovirus 71 detected frequently in fatal cases, limited attention has been paid to CVA2 infections because of its benign clinical course. In the present study, we identified three CVA2 strains from HFMD infections and used the cell-adapted CVA2 strain HN202009 to inoculate 5-day-old BALB/c mice intramuscularly. These mice developed remarkably neurological symptoms such as ataxia, hind-limb paralysis, and death. Histopathological determination showed neuronophagia, pulmonary hemorrhage, myofiberlysis and viral myocarditis. Viral replication was detected in multiple organs and tissues, and CVA2 exhibited strong tropism to muscle tissue. The severity of illness was associated with abnormally high levels of inflammatory cytokines, including interleukin (IL)-6, IL-10, tumor necrosis factor α, and monocyte chemotactic protein 1, although the blockade of these proinflammatory cytokines had no obvious protection. We also tested whether an experimental formaldehyde-inactivated CVA2 vaccine could induce protective immune response in adult mice. The CVA2 antisera from the vaccinated mice were effective against CVA2 infection. Moreover, the inactivated CVA2 vaccine could successfully generate immune protection in neonatal mice. Our results indicated that the neonatal mouse model could be a useful tool to study CVA2 infection and to develop CVA2 vaccines.
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http://dx.doi.org/10.3389/fmicb.2021.658093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192712PMC
May 2021

MicroRNAs Regulating Mitochondrial Function in Cardiac Diseases.

Front Pharmacol 2021 28;12:663322. Epub 2021 May 28.

The State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guizhou, China.

Mitochondria are the key organelles that supply cellular energy. As the most active organ in the body, the energy required to maintain the mechanical function of the heart requires a high quantity of high-quality mitochondria in cardiomyocytes. MicroRNAs (miRNAs) are single-stranded noncoding RNAs, approximately 22 nt in length, which play key roles in mediating post-transcriptional gene silencing. Numerous studies have confirmed that miRNAs can participate in the occurrence and development of cardiac diseases by regulating mitochondrial function-related genes and signaling pathways. Therefore, elucidating the crosstalk that occurs between miRNAs and mitochondria is important for the prevention and treatment of cardiac diseases. In this review, we discuss the biogenesis of miRNAs, the miRNA-mediated regulation of major genes involved in the maintenance of mitochondrial function, and the effects of miRNAs on mitochondrial function in cardiac diseases in order to provide a theoretical basis for the clinical prevention and treatment of cardiac disease and the development of new drugs.
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http://dx.doi.org/10.3389/fphar.2021.663322DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194257PMC
May 2021

CD36 deficiency ameliorates drug-induced acute liver injury in mice.

Mol Med 2021 06 6;27(1):57. Epub 2021 Jun 6.

Department of Biotherapy, Medical Center for Digestive Diseases, Second Affiliated Hospital of Nanjing Medical University, Nanjing, 210011, China.

Background: Acetaminophen (APAP) overdose causes hepatotoxicity and even acute liver failure. Recent studies indicate that sterile inflammation and innate immune cells may play important roles in damage-induced hepatocytes regeneration and liver repair. The scavenger receptor CD36 has its crucial functions in sterile inflammation. However, the roles of CD36 in APAP induced acute liver injury remain unclear and warrant further investigation.

Methods: WT C57BL/6 J and CD36 mice were intraperitoneally injected with APAP (300 mg/kg) after fasting for 16 h. Liver injury was evaluated by serum alanine aminotransferase (ALT) level and liver tissue hematoxylin and eosin (H&E) staining. Liver inflammatory factor expression was determined by real-time polymerase chain reaction (PCR). The protein adducts forming from the metabolite of APAP and the metabolism enzyme cytochrome P450 2E1 (CYP2E1) levels were measured by Western blot. Liver infiltrating macrophages and neutrophils were characterized by flow cytometry. RNA sequencing and Western blot were used to evaluate the effect of damage-associated molecular patterns (DAMP) molecule high mobility group B1 (HMGB1) on WT and CD36 macrophages. Moreover, PP2, a Src kinase inhibitor, blocking CD36 signaling, was applied in APAP model.

Results: The expression of CD36 was increased in the liver of mice after APAP treatment. Compared with WT mice, APAP treated CD36 mice show less liver injury. There was no significant difference in APAP protein adducts and CYP2E1 expression between these two strains. However, reduced pro-inflammatory factor mRNA expression and serum IL-1β level were observed in APAP treated CD36 mice as well as infiltrating macrophages and neutrophils. Moreover, CD36 deficiency impaired the activation of c-Jun N-terminal kinase (JNK) caused by APAP. Interestingly, the lack of CD36 reduced the activation of extracellular regulated protein kinases (Erk) and v-akt murine thymoma viral oncogene homolog (Akt) induced by HMGB1. RNA transcription sequencing data indicated that HMGB1 has a different effect on WT and CD36 macrophages. Furthermore, treatment with PP2 attenuated APAP induced mouse liver injury.

Conclusion: Our data demonstrated that CD36 deficiency ameliorated APAP-induced acute liver injury and inflammatory responses by decreasing JNK activation. CD36 might serve as a new target to reduce acute liver injury.
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http://dx.doi.org/10.1186/s10020-021-00325-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182905PMC
June 2021

Amphiphilic block versus random copolymer nanoparticles with reactive oxygen species responsiveness as berberine vehicles.

J Biomater Sci Polym Ed 2021 Sep 17;32(13):1657-1677. Epub 2021 Jun 17.

The State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, Guizhou, China.

A series of amphiphilic block and random copolymers based on phenylboronic acid pinacol ester were synthesized reversible addition-fragmentation chain transfer polymerization. The obtained copolymers can self-assemble in aqueous solution into stable block copolymer nanoparticles and random nanoparticles with sizes of 116.1-158.6 and 126.3-187.0 nm, respectively. All nanoparticles showed hydrogen peroxide (HO) sensitivity, and the random copolymer nanoparticles presented faster responsiveness to HO than did those derived from block copolymers. Berberine (BBR) can be effectively encapsulated into block and random copolymer nanoparticles with loading capacity of 7.6%-9.1% and 7.3%-8.9%, respectively. The BBR release can be controlled in an HO medium. For the random copolymer nanoparticles, the release rate of BBR was faster and the cumulative release amounts in response to HO were higher over 48 h. The BBR cumulative release amount in the HO medium for the block and random copolymer nanoparticles was 62.2%-70.2% and 68.6%-80.4%, respectively. Moreover, good biocompatibility was observed for the BBR-loaded block and random copolymer nanoparticles. BBR and BBR-loaded nanoparticles can improve Glut4 translocation to the cell membrane and promote glucose transport into cells. BBR-loaded nanoparticles can decrease the blood glucose levels in diabetic rats over 15 days. These results imply that the different chain formulation of block and random copolymers affects the HO responsiveness and that the two kinds of nanoparticles exhibit potential application as novel vehicles for BBR delivery to regulate blood glucose levels.
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http://dx.doi.org/10.1080/09205063.2021.1932356DOI Listing
September 2021

Biofuel Options for Marine Applications: Technoeconomic and Life-Cycle Analyses.

Environ Sci Technol 2021 06 17;55(11):7561-7570. Epub 2021 May 17.

U.S. Department of Transportation, Maritime Administration (MARAD), Washington, District of Columbia 20590, United States.

This study performed technoeconomic and life-cycle analyses to assess the economic feasibility and emission benefits and tradeoffs of various biofuel production pathways as an alternative to conventional marine fuels. We analyzed production pathways for (1) Fischer-Tropsch diesel from biomass and cofeeding biomass with natural gas or coal, (2) renewable diesel via hydroprocessed esters and fatty acids from yellow grease and cofeeding yellow grease with heavy oil, and (3) bio-oil via fast pyrolysis of low-ash woody feedstock. We also developed a new version of the Greenhouse gases, Regulated Emissions, and Energy use in Transportation (GREET) marine fuel module for the estimation of life-cycle greenhouse gas (GHG) and criteria air pollutant (CAP) emissions of conventional and biobased marine fuels. The alternative fuels considered have a minimum fuel selling price between 2.36 and 4.58 $/heavy fuel oil gallon equivalent (HFOGE), and all exhibit improved life-cycle GHG emissions compared to heavy fuel oil (HFO), with reductions ranging from 40 to 93%. The alternative fuels also exhibit reductions in sulfur oxides and particulate matter emissions. Additionally, when compared with marine gas oil and liquified natural gas, they perform favorably across most emission categories except for cases where carbon and sulfur emissions are increased by the cofed fossil feedstocks. The pyrolysis bio-oil offers the most promising marginal CO abatement cost at less than $100/tonne COe for HFO prices >$1.09/HFOGE followed by Fischer-Tropsch diesel from biomass and natural gas pathways, which fall below $100/tonne COe for HFO prices >$2.25/HFOGE. Pathways that cofeed fossil feedstocks with biomass do not perform as well for marginal CO abatement cost, particularly at low HFO prices. This study indicates that biofuels could be a cost-effective means of reducing GHG, sulfur oxide, and particulate matter emissions from the maritime shipping industry and that cofeeding biomass with natural gas could be a practical approach to smooth a transition to biofuels by reducing alternative fuel costs while still lowering GHG emissions, although marginal CO abatement costs are less favorable for the fossil cofeed pathways.
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http://dx.doi.org/10.1021/acs.est.0c06141DOI Listing
June 2021

The association between postoperative complications and prognosis in patients receiving extracorporeal membrane oxygenation in cardiac care unit.

Am J Transl Res 2021 15;13(3):1685-1691. Epub 2021 Mar 15.

Department of Cardiovascular Medicine, The First Affiliated Hospital of Airforce Military Medical University Xi'an 710032, Shaanxi, China.

Objective: To investigate the association between postoperative complications and prognosis in critically illed patients receiving extracorporeal membrane oxygenation (ECMO), so as to improve the survival rate of patients in cardiac care unit (CCU).

Methods: 43 patients who received adjuvant therapy with ECMO in our hospital were retrospectively collected and divided into survival group (n=23) and death group (n=20) according to their survival and death during hospitalization. Patients in both groups were treated with ECMO adjuvant therapy. The levels of serum total bilirubin (STB), alanine transaminase (ALT), creatine (Cr), lactic acid (Lac) and urine volume in two groups were evaluated, and the postoperative complications of two groups were observed.

Results: ECMO was performed as adjuvant therapy in both groups. The serum levels of STB, ALT, Cr and Lac in survival group were significantly lower than those in death group ( < 0.05). The number of complications such as hemorrhage, infection, renal failure, multiple organ failure (n>3) and ischemic necrosis of lower extremities in survival group was significantly less than that in death group.

Conclusion: ECMO can significantly improve the survival rate of patients in CCU. When the serum levels of STB, ALT, Cr and Lac decrease and urine volume increases, liver and kidney function injury is mild, with less postoperative complications and good prognosis. Therefore, monitoring STB, ALT, Cr, Lac and urine volume is able to adjust treatment plan in time, reduce postoperative complications and improve prognosis quality, thus has great positive clinical significance.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014358PMC
March 2021

Sphingosine 1-phosphate and osteoporosis: pathophysiology and therapeutic aspects-a narrative review.

Ann Palliat Med 2021 Apr 26;10(4):4799-4805. Epub 2021 Mar 26.

Department of Orthopaedics, Xiangya Hospital, Central South University, Changsha, China; National Clinical Research Centre for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.

Sphingosine 1-phosphate (S1P) regulates many cellular functions, such as differentiation, proliferation, migration, morphogenesis, cytoskeletal organization, adhesion, tight junction assembly, apoptosis and the localization of different cell types. S1P also controls the migration of osteoclast precursors between the blood and bone, and it keeps osteoclast precursors away from bone surfaces to reduce bone degradation, thus preventing bone decay. Osteoporosis is a systemic bone disease that predisposes patients to bone fracture due to decreased bone density and quality, disrupted bone microarchitecture, and increased bone fragility. As the global elderly population increases, the incidence of osteoporosis will greatly increase, and the associated adverse consequences will become more serious. S1P plays an important role in homeostasis, and disruption of the balance between osteoblasts and osteoclasts may induce osteoporosis. A high frequency of osteoporotic fracture is associated with increased plasma S1P levels. Studies have shown that S1P is an important therapeutic target in osteoporosis because it controls the migration of osteoclast precursors, vigorously maintains the bone mineralization process, and is a critical regulator of osteoclastogenesis. Improved understanding of the functional roles and molecular mechanisms of S1P in bone turnover could facilitate the discovery of novel targets for the treatment of osteoporosis. This review provides a critical discussion of the role of S1P in osteoporosis and treatments.
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http://dx.doi.org/10.21037/apm-20-1255DOI Listing
April 2021

Toward net-zero sustainable aviation fuel with wet waste-derived volatile fatty acids.

Proc Natl Acad Sci U S A 2021 Mar;118(13)

Catalytic Carbon Transformation Center, National Renewable Energy Laboratory, Golden, CO 80401;

With the increasing demand for net-zero sustainable aviation fuels (SAF), new conversion technologies are needed to process waste feedstocks and meet carbon reduction and cost targets. Wet waste is a low-cost, prevalent feedstock with the energy potential to displace over 20% of US jet fuel consumption; however, its complexity and high moisture typically relegates its use to methane production from anaerobic digestion. To overcome this, methanogenesis can be arrested during fermentation to instead produce C to C volatile fatty acids (VFA) for catalytic upgrading to SAF. Here, we evaluate the catalytic conversion of food waste-derived VFAs to produce n-paraffin SAF for near-term use as a 10 vol% blend for ASTM "Fast Track" qualification and produce a highly branched, isoparaffin VFA-SAF to increase the renewable blend limit. VFA ketonization models assessed the carbon chain length distributions suitable for each VFA-SAF conversion pathway, and food waste-derived VFA ketonization was demonstrated for >100 h of time on stream at approximately theoretical yield. Fuel property blending models and experimental testing determined normal paraffin VFA-SAF meets 10 vol% fuel specifications for "Fast Track." Synergistic blending with isoparaffin VFA-SAF increased the blend limit to 70 vol% by addressing flashpoint and viscosity constraints, with sooting 34% lower than fossil jet. Techno-economic analysis evaluated the major catalytic process cost-drivers, determining the minimum fuel selling price as a function of VFA production costs. Life cycle analysis determined that if food waste is diverted from landfills to avoid methane emissions, VFA-SAF could enable up to 165% reduction in greenhouse gas emissions relative to fossil jet.
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http://dx.doi.org/10.1073/pnas.2023008118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020759PMC
March 2021

Natural Killer Cells: Friend or Foe in Metabolic Diseases?

Front Immunol 2021 24;12:614429. Epub 2021 Feb 24.

Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

The worldwide epidemic of metabolic diseases, especially obesity and other diseases caused by it, has shown a dramatic increase in incidence. A great deal of attention has been focused on the underlying mechanisms of these pathological processes and potential strategies to solve these problems. Chronic inflammation initiated by abdominal adipose tissues and immune cell activation in obesity is the major cause of the consequent development of complications. In addition to adipocytes, macrophages and monocytes, natural killer (NK) cells have been verified to be vital components involved in shaping the inflammatory microenvironment, thereby leading to various obesity-related metabolic diseases. Here, we provide an overview of the roles of NK cells and the interactions of these cells with other immune and nonimmune cells in the pathological processes of metabolic diseases. Finally, we also discuss potential therapeutic strategies targeting NK cells to treat metabolic diseases.
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http://dx.doi.org/10.3389/fimmu.2021.614429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943437PMC
July 2021

Gastrodin ameliorates learning and memory impairment in rats with vascular dementia by promoting autophagy flux via inhibition of the Ca/CaMKII signal pathway.

Aging (Albany NY) 2021 03 10;13(7):9542-9565. Epub 2021 Mar 10.

The High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province and The High Educational Key Laboratory of Guizhou Province for Natural Medicinal Pharmacology and Druggability, School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang 550025, P.R. China.

Vascular dementia (VD) is a common disease that occurs during human aging. Gastrodin (GAS) has potential benefits for the prevention and treatment of VD. In the present study, we investigated the effects of GAS on cognitive dysfunction in rats with VD induced by permanent middle cerebral artery occlusion (pMCAO) and explored the underlying mechanism. Immunohistochemical and western blot analyses revealed that GAS attenuated hippocampal levels of LC3 (microtubule-associated protein 1 light chain 3), p62, and phosphorylated CaMKII (Ca-calmodulin stimulated protein kinase II) in VD rats. Additionally, our results revealed that cobalt chloride blocked autophagic flux in HT22 cells, which was confirmed by increased levels of LC3 and p62 when combined with chloroquine. Notably, GAS ameliorated the impaired autophagic flux. Furthermore, we confirmed that GAS combined with KN93 (a CaMKII inhibitor) or CaMKII knockdown did not impact the reduced p62 levels when compared with GAS treatment alone. Furthermore, a co-immunoprecipitation assay demonstrated that endogenous p62 bound to CaMKII, as confirmed by mass spectrometric analysis after the immunoprecipitation of p62 from HT22 cells. These findings revealed that GAS attenuated autophagic flux dysfunction by inhibiting the Ca/CaMKII signaling pathway to ameliorate cognitive impairment in VD.
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http://dx.doi.org/10.18632/aging.202667DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8064221PMC
March 2021

Impact of chronic obstructive pulmonary disease on 10-year mortality after percutaneous coronary intervention and bypass surgery for complex coronary artery disease: insights from the SYNTAX Extended Survival study.

Clin Res Cardiol 2021 Jul 12;110(7):1083-1095. Epub 2021 Mar 12.

Department of Cardiology, National University of Ireland, Galway (NUIG), P.O. University Road, Galway, H91 TK33, Ireland.

Aims: To evaluate the impact of chronic obstructive pulmonary disease (COPD) on 10-year all-cause death and the treatment effect of CABG versus PCI on 10-year all-cause death in patients with three-vessel disease (3VD) and/or left main coronary artery disease (LMCAD) and COPD.

Methods: Patients were stratified according to COPD status and compared with regard to clinical outcomes. Ten-year all-cause death was examined according to the presence of COPD and the revascularization strategy.

Results: COPD status was available for all randomized 1800 patients, of whom, 154 had COPD (8.6%) at the time of randomization. Regardless of the revascularization strategy, patients with COPD had a higher risk of 10-year all-cause death, compared with those without COPD (43.1% vs. 24.9%; hazard ratio [HR]: 2.03; 95% confidence interval [CI]: 1.56-2.64; p < 0.001). Among patients with COPD, CABG appeared to have a slightly lower risk of 10-year all-cause death compared with PCI (42.3% vs. 43.9%; HR: 0.96; 95% CI: 0.59-1.56, p = 0.858), whereas among those without COPD, CABG had a significantly lower risk of 10-year all-cause death (22.7% vs. 27.1%; HR: 0.81; 95% CI: 0.67-0.99, p = 0.041). There was no significant differential treatment effect of CABG versus PCI on 10-year all-cause death between patients with and without COPD (p  = 0.544).

Conclusions: COPD was associated with a higher risk of 10-year all-cause death after revascularization for complex coronary artery disease. The presence of COPD did not significantly modify the beneficial effect of CABG versus PCI on 10-year all-cause death.

Trial Registration: SYNTAX: ClinicalTrials.gov reference: NCT00114972. SYNTAX Extended Survival: ClinicalTrials.gov reference: NCT03417050.
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http://dx.doi.org/10.1007/s00392-021-01833-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8238698PMC
July 2021

Co-delivery of antibiotic and baicalein by using different polymeric nanoparticle cargos with enhanced synergistic antibacterial activity.

Int J Pharm 2021 Apr 27;599:120419. Epub 2021 Feb 27.

The State Key Laboratory of Functions and Applications of Medicinal Plants, School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guizhou 550025, China; The Department of Pharmacology of Materia Medica (the High Efficacy Application of Natural Medicinal Resources Engineering Center of Guizhou Province, the Key Laboratory of Optimal Utilization of Natural Medicine Resources), School of Pharmaceutical Sciences, Guizhou Medical University, University Town, Guian New District, Guizhou 550025, China. Electronic address:

To evaluate the effect of polymer structures on their unique characteristics and antibacterial activity, this study focused on developing amphiphilic copolymers by using three different molecules through RAFT polymerization. Three amphiphilic copolymers, namely, PBMA-b-(PDMAEMA-r-PPEGMA) (BbDrE), (PBMA-r-PDMAEMA)-b-PPEGMA (BrDbE), and PBMA-r-PDMAEMA-r-PPEGMA (BrDrE), are successfully self-assembled into spherical or oval shaped nanoparticles in aqueous solution and remain stable in PBS, LB, and 10% FBS solutions for at least 3 days. The critical micelle concentrations are 0.012, 0.025, and 0.041 mg/mL for BbDrE, BrDbE, and BrDrE, respectively. The zeta potential values under pH 5.5 and pH 7.4 conditions are 3.18/0.19, 8.57/0.046, and 2.54/-0.69 mV for BbDrE, BrDbE, and BrDrE nanoparticles, respectively. The three copolymers with similar monomer compositions show similar molecular weight and thermostability. Baicalein (BA) and ciprofloxacin (CPX) are encapsulated into the three nanoparticles to obtain [email protected]/CPX, [email protected]/CPX, and [email protected]/CPX nanocomposites, with LC values of 63.9/78.3, 63.9/74.7, and 55.3/64.8, respectively. The two drugs are released from the three drug-loaded nanocomposites with 60%-95% release in pH 5.5 over 24 h and 15%-30% release in pH 7.4. The drug-loaded nanocomposites show synergistic antibacterial activity than the naked drug (2-8 fold reduction for CPX) or single drug-loaded nanocomposites (4-8 fold reduction for CPX) against Pseudomonas aeruginosa and Staphylococcus aureus. The drug-loaded nanocomposites inhibit the formation of bacterial biofilms above their MIC values and eliminate bacterial biofilms observed by fluorescent microscope. Finally, the nanocomposites improve the healing of infection induced by P. aeruginosa and S. aureus on rat dermal wounds. These results indicate that antimicrobial agents with different structures could be an alternative treatment strategy for bacteria-induced infection.
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http://dx.doi.org/10.1016/j.ijpharm.2021.120419DOI Listing
April 2021

Different distribution patterns of microorganisms between aquaculture pond sediment and water.

J Microbiol 2021 Apr 25;59(4):376-388. Epub 2021 Feb 25.

Key Laboratory of Freshwater Biodiversity Conservation, Ministry of Agriculture and Rural Affairs, Yangtze River Fisheries Research Institute, Chinese Academy of Fishery Sciences, Wuhan, 100141, P. R. China.

Aquatic microorganisms in the sediment and water column are closely related; however, their distribution patterns between these two habitats still remain largely unknown. In this study, we compared sediment and water microeukaryotic and bacterial microorganisms in aquaculture ponds from different areas in China, and analyzed the influencing environmental factors as well as the inter-taxa relationships. We found that bacteria were significantly more abundant than fungi in both sediment and water, and the bacterial richness and diversity in sediment were higher than in water in all the sampling areas, but no significant differences were found between the two habitats for microeukaryotes. Bacterial taxa could be clearly separated through cluster analysis between the sediment and water, while eukaryotic taxa at all classification levels could not. Spirochaetea, Deltaproteobacteria, Nitrospirae, Ignavibacteriae, Firmicutes, Chloroflexi, and Lentimicrobiaceae were more abundantly distributed in sediment, while Betaproteobacteria, Alphaproteobacter, Cyanobacteria, Roseiflexaceae, Dinghuibacter, Cryomorphaceae, and Actinobacteria were more abundant in water samples. For eukaryotes, only Cryptomonadales were found to be distributed differently between the two habitats. Microorganisms in sediment were mainly correlated with enzymes related to organic matter decomposition, while water temperature, pH, dissolved oxygen, and nutrient levels all showed significant correlation with the microbial communities in pond water. Intensive interspecific relationships were also found among eukaryotes and bacteria. Together, our results indicated that eukaryotic microorganisms are distributed less differently between sediment and water in aquaculture ponds compared to bacteria. This study provides valuable data for evaluating microbial distributions in aquatic environments, which may also be of practical use in aquaculture pond management.
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http://dx.doi.org/10.1007/s12275-021-0635-5DOI Listing
April 2021

Comparison of one-month versus twelve-month dual antiplatelet therapy after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome: rationale and design of prospective, multicenter, randomized, controlled IVUS-ACS and ULTIMATE-DAPT trial.

Am Heart J 2021 06 20;236:49-58. Epub 2021 Feb 20.

Division of Cardiology, Nanjing first hospital, Nanjing medical unviersity, China. Electronic address:

Background: Current guidelines recommend administering dual antiplatelet therapy (DAPT) for 12 months to patients with acute coronary syndromes (ACS) and without contraindications after drug-eluting stent (DES) implantation. A recent study reported that 3 months of DAPT followed by ticagrelor monotherapy is effective and safe in ACS patients undergoing DES implantation compared with the standard duration of DAPT. However, it is unclear whether antiplatelet monotherapy with ticagrelor alone versus ticagrelor plus aspirin reduces the incidence of clinically relevant bleeding without increasing the risk of major adverse cardiovascular and cerebrovascular events (MACCEs) in ACS patients undergoing percutaneous coronary intervention (PCI) with DES implantation guided by either intravascular ultrasound (IVUS) or angiography who have completed a 1-month course of DAPT with aspirin plus ticagrelor.

Methods: The IVUS-ACS and ULTIMATE-DAPT is a prospective, multicenter, randomized, controlled trial designed to determine (1) whether IVUS-guided versus angiography-guided DES implantation in patients with ACS reduces the risk of target vessel failure (TVF) at 12 months and (2) whether ticagrelor alone versus ticagrelor plus aspirin reduces the risk of clinically relevant bleeding without increasing the risk of MACCE 1-12 months after the index PCI in ACS patients undergoing DES implantation guided by either IVUS or angiography. This study will enroll 3486 ACS patients eligible for DES implantation, as confirmed by angiographic studies. The patients who meet the inclusion criteria and none of the exclusion criteria will be randomly assigned in a 1:1 fashion to the IVUS- or angiography-guided group (first randomization). All enrolled patients will complete a 1-month course of DAPT with aspirin plus ticagrelor after the index PCI. Patients with no MACCEs or major bleeding (≥Bleeding Academic Research Consortium (BARC) 3b) within 30 days will be randomized in a 1:1 fashion to either the ticagrelor plus matching placebo (SAPT)group or ticagrelor plus aspirin (DAPT)group for an additional 11 months (second randomization). The primary endpoint of the IVUS-ACS trial is TVF at 12 months, including cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (CD-TVR). The primary superiority endpoint of the ULTIMATE-DAPT trial is clinically relevant bleeding, defined as BARC Types 2, 3, or 5 bleeding, and the primary non-inferiority endpoint of the ULTIMATE-DAPT trial is MACCE, defined as cardiac death, myocardial infarction, ischemic stroke, CD-TVR, or definite stent thrombosis occurring 1-12 months in the second randomized population.

Conclusion: The IVUS-ACS and ULTIMATE-DAPT trial is designed to test the efficacy and safety of 2 different antiplatelet strategies in ACS patients undergoing PCI with DES implantation guided by either IVUS or angiography. This study will provide novel insights into the optimal DAPT duration in ACS patients undergoing PCI and provide evidence on the clinical benefits of IVUS-guided PCI in ACS patients.
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http://dx.doi.org/10.1016/j.ahj.2021.02.014DOI Listing
June 2021

Nine-month angiographic and 2-year clinical outcomes of the RECOVERY trial: A randomized study of the biodegradable polymer sirolimus-eluting COMBO dual-therapy stent versus a polymer-free sirolimus-eluting stent in Chinese patients.

Catheter Cardiovasc Interv 2021 May 19;97 Suppl 2:966-975. Epub 2021 Feb 19.

Catheterization Laboratories, Fu Wai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, National Clinical Research Center for Cardiovascular Diseases, Beijing, China.

Objectives: We evaluated the safety and efficacy of the novel dual-therapy sirolimus-eluting and endothelial progenitor cell (EPC) capture COMBO stent.

Background: (Very) late stent thrombosis (ST) and neo-atherosclerosis limit the performance of drug-eluting stents. The capture of EPCs accelerates stent re-endothelialization, thereby potentially decreasing the risk of restenosis and ST.

Methods: In total, 440 patients with de novo lesions in native coronary arteries were randomized (1:1) to either receive the COMBO stent (n = 220) or Nano polymer-free sirolimus-eluting stent (n = 220). The primary endpoint was the 9-month angiographic in-segment late lumen loss (LLL). Secondary endpoints included target lesion failure (TLF), a patient-oriented composite endpoint (PoCE), and ST.

Results: At 9 months, the COMBO in-segment LLL (0.29 ± 0.46 mm) was non-inferior to that of the Nano comparator stent (0.31 ± 0.44 mm; p  < .0001). Clinical outcomes were also similar between the COMBO and Nano stents, with TLF rates of 9.3% and 7.9% (p = .61) at 12 months, and 9.4% and 8.0% (p = .62) at 24 months, respectively. The PoCE rate was 14.8% and 10.6% (p = .19) at 12 months, and 16.0% and 11.3% (p = .16) at 24 months, respectively. Ischemia-driven target lesion revascularization rates were 6.0% and 3.7% (p = .26) at 12 months, and 6.2% and 3.8% (p = .26) at 24 months, respectively. No case of ST occurred in either group.

Conclusions: The RECOVERY trial has shown the COMBO stent was effective, meeting the primary non-inferiority angiographic endpoint, and safe, with an overall low rate of clinical events in both stent groups, including no ST for up to 2 years.
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http://dx.doi.org/10.1002/ccd.29553DOI Listing
May 2021

The CB index predicts prognosis of critically ill COVID-19 patients.

Ann Transl Med 2020 Dec;8(24):1654

Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Background: The global outbreak of COVID-19 is a significant threat to public health. Among COVID-19 cases, critically ill patients account for most in-hospital deaths. Given the pressing clinical needs, identification of potential prognostic factors that would assist clinicians to determine appropriate therapeutic interventions is urgently needed.

Methods: A retrospective analysis of 171 critically ill COVID-19 patients from two medical centers in Wuhan was conducted. The training and validation cohorts were comprised of 77 and 94 patients, respectively. Univariate and multivariate Logistic regression analyses were used to identify independent prognostic factors, and the linear prediction index was established and externally validated.

Results: Blood urine nitrogen (BUN) and high-sensitive C-reactive protein (hs-CRP) were independent factors negatively correlated with patient survival in the training cohort. A linear prediction model, named as the CB index (hs-CRP combined with BUN), was established and logistic regression analysis showed that this was associated with a 13% increase in death rate, with high sensitivity (86.7%) and specificity (89.7%). Patients were then divided into a high-risk group (CB index >32) and low-risk group (CB index <32) and the high-risk group showed a 56.3-fold risk of death compared with the low-risk group. Importantly, these findings were readily recaptured in the validation cohort. The efficacy of the CB index in predicting prognosis in real-world patients was then determined, which showed that patients with a higher CB index had an increased risk of death in comparison to those with a lower CB index.

Conclusions: The CB index may be an important prognostic factor in critically ill COVID-19 patients.
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http://dx.doi.org/10.21037/atm-20-7447DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812180PMC
December 2020

Assessment of cultured media for desert moss crust by physiological responses.

J Basic Microbiol 2021 Feb 4;61(2):157-164. Epub 2021 Jan 4.

School of Environmental and Municipal Engineering, Lanzhou Jiaotong University, Lanzhou, China.

The physiological responses of desert moss crusts under four artificial media (Beneck, Part, BG11, and Hogland) were investigated to evaluate the function of culture media during different culture periods. The results showed that the value of malondialdehyde (MDA) was at a maximum at 11d, on the contrary, chlorophyll-a, soluble protein, and soluble sugar were at a minimum. As the time increased, the value of MDA and soluble protein decreased faster in the Hogland, while the value of chlorophyll-a and soluble sugar increased. At the end of the culture period, the value of chlorophyll-a and soluble sugar was at a maximum in the Hogland, while the value of MDA and soluble protein was at a minimum. The results suggested that the Hogland medium had a promoting effect on the growth of desert moss crusts. The selected artificial cultivation medium towards wider and larger scale field applications of cultural desert biocrust was widely anticipated.
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http://dx.doi.org/10.1002/jobm.202000665DOI Listing
February 2021
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