Publications by authors named "Tong Zhu"

686 Publications

Novel 2-phenyl-3-(Pyridin-2-yl) thiazolidin-4-one derivatives as potent inhibitors for proliferation of osteosarcoma cells in vitro and in vivo.

Eur J Med Chem 2021 Nov 26;228:114010. Epub 2021 Nov 26.

Shanghai Engineering Research Center of Molecular Therapeutics and New Drug Development, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai, 200062, PR China. Electronic address:

Due to unknown pathogenesis and unidentified drug target, no drug for the treatment of osteosarcoma (OS) has been launched to the market. Herein, thiazolidinone 1a was discovered as a hit compound by phenotypic screening with an in-house patrimonial collection of structural diversity. The following SAR (Structure-Activity Relationship) study affords the final water-soluble lead compound (R)-8i as a potential inhibitor for the proliferation of OS cells by the modulation of solubility of the compounds with remarkable cellular potency (IC = 21.9 nM for MNNG/HOS cells) and in vivo efficacy (52.9% inhibition OS growth in mice), as well as pharmacokinetic properties. (R)-8i also significantly suppresses OS cell migration in vitro and showed to be well-tolerated. Our preliminary investigation shows that the effects of (R)-8i are not dependent on p53 and myoferlin (MYOF). These results suggest that (R)-8i might be a potential drug candidate for OS treatment.
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http://dx.doi.org/10.1016/j.ejmech.2021.114010DOI Listing
November 2021

Pan-cancer multi-omics analyses reveal crosstalk between the Hippo and immune signaling pathways in the tumor microenvironment.

FEBS Lett 2021 Dec 2. Epub 2021 Dec 2.

The Sino-Russian Medical Research Center of Jinan University, the Institute of Chronic Disease of Jinan University, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, 510080, China.

The Hippo signaling pathway is critical for carcinogenesis. However, the roles of the Hippo signaling pathway in the tumor immune microenvironment have been rarely investigated. This study systematically analyzed the relationship between the Hippo signaling pathway and immune cell infiltration across 32 cancer types. Both bioinformatics analyses and biological experiments revealed that the downstream effector of Hippo signaling YAP1 might inhibit CD8+ T cell infiltration by upregulating the expression of the transcription factor CREB1 in uterine corpus endometrial carcinoma. In addition, esophageal carcinoma (ESCA) patients were classified into three subtypes based on the Hippo-immune gene panel. The subtypes of ESCA had distinct characteristics in immune cell infiltration, immune pathways, and prognosis. Thus, this study also reveals a new classification of the immune subtypes with prognostic characteristics in ESCA.
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http://dx.doi.org/10.1002/1873-3468.14249DOI Listing
December 2021

Generation of duck Tembusu virus using a simple reverse genetic system in duck embryo fibroblast cells.

J Virol Methods 2021 Nov 26:114385. Epub 2021 Nov 26.

Institute of Poultry Science, Shandong Academy of Agricultural Sciences / Shandong Provincial Key Laboratory of Immunity and Diagnosis of Poultry Diseases, No. 1 Jiaoxiao Road, Jinan, Shandong, 250023, China. Electronic address:

Outbreaks of duck Tembusu virus (DTMUV) have caused serious economic losses in China since 2010. In this study, an infectious clone of the DTMUV BZ-2010strain, isolated from layer cherry duck in China, was constructed using the bacterium-free infectious subgenomic-amplicons method. The subgenomic-amplicons of the human cytomegalovirus promoter (pCMV) at the 5' terminus of the first DNA fragment, the entire genome of DTMUV, and the hepatitis delta ribozyme followed by the simian virus 40 polyadenylation signal (HDR/SV40pA) at the 3' terminus of the last DNA fragment were synthesized and amplified by PCR in three DNA fragments. The pCMV and HDR/SV40pA were used to drive the viral RNA transcription and generate a full-length RNA transcript of the virus, and were found to be effective in reassembling DTMUV in duck embryo fibroblast cells. The RNA transcripts from the infection clone were infectious in duck embryo fibroblast cells, generating the reconstituted DTMUV. This study provided a valuable reverse genetic tool for the further study DTMUV pathogenesis.
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http://dx.doi.org/10.1016/j.jviromet.2021.114385DOI Listing
November 2021

Low-dose dobutamine cardiovascular magnetic resonance segmental strain study of early phase of intramyocardial hemorrhage rats.

BMC Med Imaging 2021 11 20;21(1):173. Epub 2021 Nov 20.

Department of Radiology, West China Hospital, Sichuan University, 37 Guo Xuexiang Road, Wuhou District, Chengdu, 610041, Sichuan, China.

Background: This study investigates the segmental myocardial strain of the early phase of intramyocardial hemorrhage (IMH) caused by reperfused myocardial infarction (MI) in rats by low-dose dobutamine (LDD) cardiovascular magnetic resonance (CMR) feature-tracking.

Methods: Nine sham rats and nine rats with 60-min myocardial ischemia followed by 48-h reperfusion were investigated using CMR, including T2*-mapping sequence and fast imaging with steady-state precession (FISP)-cine sequence. Another FISP-cine sequence was acquired after 2 min of dobutamine injection; the MI, IMH, and Non-MI (NMI) areas were identified. The values of peak radial strains (PRS) and peak circumferential strains (PCS) of the MI, IMH and NMI segments were acquired. The efficiency of PRS and PCS (EPRS and EPCS, respectively) were calculated on the basis of the time of every single heartbeat.

Results: The PRS, PCS, EPRS, and EPCS of the sham group increased after LDD injection. However, the PRS, PCS, EPRS, and EPCS of the IMH segment did not increase. Moreover, the PRS and PCS of the MI and NMI segments did not increase, but the EPRS and EPCS of these segments increased. The PRS, PCS, EPRS, and EPCS of the IMH segment were lower than those of the MI and NMI segments before and after LDD injection, but without a significant difference between MI segment and NMI segment before and after LDD injection.

Conclusions: LDD could help assess dysfunctions in segments with IMH, especially using the efficiency of strain. IMH was a crucial factor that decreased segmental movement and reserved function.
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http://dx.doi.org/10.1186/s12880-021-00709-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605595PMC
November 2021

Rigid Conjugated Diamine Templates for Stable Dion-Jacobson-Type Two-Dimensional Perovskites.

J Am Chem Soc 2021 Dec 17;143(47):19901-19908. Epub 2021 Nov 17.

Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario M5S 3H6, Canada.

Hybrid organic-inorganic perovskites (HOIPs) have garnered widespread interest, yet stability remains a critical issue that limits their further application. Compared to their three-dimensional (3D) counterparts, two-dimensional (2D)-HOIPs exhibit improved stability. 2D-HOIPs are also appealing because their structural and optical properties can be tuned according to the choice of organic ligand, with monovalent or divalent ligands forming Ruddlesden-Popper (RP) or Dion-Jacobson (DJ)-type 2D perovskites, respectively. Unlike RP-type 2D perovskites, DJ-type 2D perovskites do not contain a van der Waals gap between the 2D layers, leading to improved stability. However, bifunctional organic ligands currently used to develop DJ-type 2D perovskites are limited to commercially available aliphatic and single-ring aromatic ammonium cations. Large conjugated organic ligands are in demand for their semiconducting properties and their potential to improve materials stability further. In this manuscript, we report the design and synthesis of a new set of larger conjugated diamine ligands and their incorporation into DJ-type 2D perovskites. Compared with analogous RP-type 2D perovskites, DJ 2D perovskites reported here show blue-shifted, narrower emissions and significantly improved stability. By changing the structure of rings (benzene vs thiophene) and substituents, we develop structure-property relationships, finding that fluorine substitution enhances crystallinity. Single-crystal structure analysis and density functional theory calculations indicate that these changes are due to strong electrostatic interactions between the organic templates and inorganic layers as well as the rigid backbone and strong π-π interaction between the organic ligands themselves. These results illustrate that targeted engineering of the diamine ligands can enhance the stability of DJ-type 2D perovskites.
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http://dx.doi.org/10.1021/jacs.1c09515DOI Listing
December 2021

Covered cheatham-platinum stent for treatment of descending thoracic aortic stenosis caused by Takayasu arteritis in two children.

Ann Vasc Surg 2021 Nov 11. Epub 2021 Nov 11.

Department of Vascular Surgery, Xuanwu Hospital, Capital Medical University, Beijing, China. Electronic address:

Takayasu arteritis (TA) is a chronic type of systemic large vessel vasculitis, mainly involving the aorta and its main branches. Both surgical and endovascular revascularization are effective methods for treating TA-related stenosis of the aorta and its branches. By December 2020, there have been very limited reports on the use of coated Cheatham-Platinum (CP) stents in the treatment of TA associated descending thoracic aortic stenosis. Two children with thoracic aortic stenosis caused by TA who received the covered CP stent in Xuanwu Hospital of Capital Medical University were reported. The follow-up time was 1.5 years and 4 years, respectively. The covered cheatham-platinum (CP) stent may be an alternative treatment for TA associated children with descending aortic stenosis.
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http://dx.doi.org/10.1016/j.avsg.2021.09.034DOI Listing
November 2021

Electric Bicyclist Injury Severity during Peak Traffic Periods: A Random-Parameters Approach with Heterogeneity in Means and Variances.

Int J Environ Res Public Health 2021 10 22;18(21). Epub 2021 Oct 22.

Department of Civil, Construction and Environmental Engineering, The University of Alabama, Tuscaloosa, AL 35487, USA.

Accidents involving electric bicycles, a popular means of transportation in China during peak traffic periods, have increased. However, studies have seldom attempted to detect the unique crash consequences during this period. This study aims to explore the factors influencing injury severity in electric bicyclists during peak traffic periods and provide recommendations to help devise specific management strategies. The random-parameters logit or mixed logit model is used to identify the relationship between different factors and injury severity. The injury severity is divided into four categories. The analysis uses automobile and electric bicycle crash data of Xi'an, China, between 2014 and 2019. During the peak traffic periods, the impact of low visibility significantly varies with factors such as areas with traffic control or without streetlights. Furthermore, compared with traveling in a straight line, three different turnings before the crash reduce the likelihood of severe injuries. Roadside protection trees are the most crucial measure guaranteeing riders' safety during peak traffic periods. This study reveals the direction, magnitude, and randomness of factors that contribute to electric bicycle crashes. The results can help safety authorities devise targeted transportation safety management and planning strategies for peak traffic periods.
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http://dx.doi.org/10.3390/ijerph182111131DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8582883PMC
October 2021

Associations between differences in anemia-related blood cell parameters and short-term exposure to ambient particle pollutants in middle-aged and elderly residents in Beijing, China.

Sci Total Environ 2021 Nov 9:151520. Epub 2021 Nov 9.

SKL-ESPC and BIC-ESAT, College of Environmental Sciences and Engineering, Peking University, Beijing, China. Electronic address:

Anemia is a highly prevalent disease among older populations, with multiple adverse health outcomes, and particles exposure is a potential risk factor for anemia. However, evidence on associations of exposure to particles with small size with anemia-related blood cell parameters levels in the elderly is limited, and the underlying mechanisms are unclear. Based on a panel study in Beijing, we found that in 135 elderly participants, mass concentrations of particle with an aerodynamic diameter ≤ 2.5 μm (PM), black/elemental carbon (BC/EC, particle size range: 0-2.5 μm), and number concentrations of ultrafine particles (UFPs, particle size range: 5.6-93.1 nm) and accumulated mode particles (Acc, size range: 93.1-560 nm) were significantly associated with levels of red blood cell count (RBC), hemoglobin (HGB), hematocrit (HCT), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC). The mean ± SD for PM, UFPs, Acc, BC, OC, and EC were 69.7 ± 61.1 μg/m, 12.5 ± 4.3 × 10/cm, 1.6 ± 1.2 × 10/cm, 3.0 ± 2.0 μg/m, 8.7 ± 6.7 μg/m, and 2.1 ± 1.6 μg/m, respectively. Cotinine (higher than 50 ng/mL) is used as an indicator of smoking exposure. The association between MCHC difference and per interquartile range (IQR) increase in average UFPs concentration 14 d before clinical visits was -0.7% (95% CI: -1.1% to -0.3%). Significant associations of UFPs and Acc exposure with MCHC and MCH levels remain robust after adjustment for other pollutants. Furthermore, 25.2% (95% CI: 7.4% to 64.8%) and 29.8% (95% CI: 5.3% to 214.4%) of the difference in MCHC associated with average UFPs and Acc concentrations 14 d before clinical visits were mediated by the level of tumor necrosis factor α (TNF α), a biomarker of systemic inflammation. Our findings for the first time provide the evidence that short-term UFPs and Acc exposure contributed to the damage of anemia-related blood cell in the elderly, and systemic inflammation was a potential internal mediator.
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http://dx.doi.org/10.1016/j.scitotenv.2021.151520DOI Listing
November 2021

Water as a probe for pH measurement in individual particles using micro-Raman spectroscopy.

Anal Chim Acta 2021 Nov 23;1186:339089. Epub 2021 Sep 23.

BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, 100871, China. Electronic address:

Atmospheric aerosol acidity impacts numerous physicochemical processes, but the determination of particle pH remains a significant challenge due to the nonconservative nature of the H concentration ([H]). Traditional measurements have difficulty in describing the practical state of an aerosol because they comprise chemical components or hypotheses that change the nature of the particles. In this work, we present a direct pH measurement that uses water as a general probe to detect [H] in individual particles by micro-Raman spectroscopy. Containing the vibrational bands of ions and water influenced by ions, the spectra of hydrated ion were decomposed from the solution spectra as standard spectra by multivariate curve resolution analysis. Meanwhile, ratios of hydrated ions were calculated between the Raman spectra and standard spectra to evaluate concentration profiles of each ion. It demonstrated that good quantitative models between the ratio and concentration for all ions including H can be built with correlation coefficients (R) higher than 0.95 for the solutions. The method was further applied to individual particle pH measurement. The pH value of sulfate aerosol particles was calculated, and the standard error was 0.09 using pH values calculated from the [HSO]/[SO] as a reference. Furthermore, the applicability of the method was proven by detecting the pH value of chloride particles. Therefore, utilizing water, the most common substance, as the spectroscopic probe to measure [H] without restriction of the ion system, this method has potential to measure the pH value of atmospheric particles with various compounds, although more work needs to be done to improve the sensitivity of the method.
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http://dx.doi.org/10.1016/j.aca.2021.339089DOI Listing
November 2021

Automated Construction of Neural Network Potential Energy Surface: The Enhanced Self-Organizing Incremental Neural Network Deep Potential Method.

J Chem Inf Model 2021 11 9;61(11):5425-5437. Epub 2021 Nov 9.

Shanghai Engineering Research Center of Molecular Therapeutics & New Drug Development, Shanghai Key Laboratory of Green Chemistry & Chemical Process, School of Chemistry and Molecular Engineering, East China Normal University, Shanghai 200062, China.

In recent years, the use of deep learning (neural network) potential energy surface (NNPES) in molecular dynamics simulation has experienced explosive growth as it can be as accurate as quantum chemistry methods while being as efficient as classical mechanic methods. However, the development of NNPES is highly nontrivial. In particular, it has been troubling to construct a dataset that is as small as possible yet can cover the target chemical space. In this work, an ESOINN-DP method is developed, which has the enhanced self-organizing incremental neural network (ESOINN) and a newly proposed error indicator at its core. With ESOINN-DP, one can construct the NNPES with little human intervention, and this method ensures that the constructed reference dataset covers the target chemical space with minimum redundancy. The performance of the ESOINN-DP method has been well validated by developing neural network potential energy surfaces for water clusters, tripeptides, and by de-redundancy of a sub-dataset of the ANI-1 database. We believe that the ESOINN-DP method provides a novel idea for the construction of NNPES and, especially, the reference datasets, and it can be used for molecular dynamics (MD) simulations of various gas-phase and condensed-phase chemical systems.
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http://dx.doi.org/10.1021/acs.jcim.1c01125DOI Listing
November 2021

Recommended Best Practices for Lyophilization Validation 2021 Part II: Process Qualification and Continued Process Verification.

AAPS PharmSciTech 2021 Nov 8;22(8):266. Epub 2021 Nov 8.

Birck Nanotechnology Center, Purdue University, 1205 W State St., West Lafayette, IN, 47907, USA.

This work describes the lyophilization process validation and consists of two parts. Part one (Part I: Process Design and Modeling) focuses on the process design and is described in the previous paper, while the current paper is devoted to process qualification and continued process verification. The goal of the study is to show the cutting edge of lyophilization validation based on the integrated community-based opinion and the industrial perspective. This study presents best practices for batch size determination and includes the effect of batch size on drying time, process parameters selection strategies, and batch size overage to compensate for losses during production. It also includes sampling strategies to demonstrate batch uniformity as well as the use of statistical models to ensure adequate sampling. Based on the LyoHUB member organizations survey, the best practices in determining the number of PPQ runs are developed including the bracketing approach with minimum and maximum loads. Standard practice around CQA and CPP selection is outlined and shows the advantages of using control charts and run charts for process trending and quality control. The case studies demonstrating the validation strategy for monoclonal antibody and the impact of the loading process on the lyophilization cycle and product quality as well as the special case of lyophilization for dual-chamber cartridge system are chosen to illustrate the process validation. The standard practices in the validation of the lyophilization process, special lyophilization processes, and their impact on the validation strategy are discussed.
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http://dx.doi.org/10.1208/s12249-021-02107-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8575750PMC
November 2021

Fine particulate matter and vasoactive 20-hydroxyeicosatetraenoic acid: Insights into the mechanisms of the prohypertensive effects of particulate air pollution.

Sci Total Environ 2022 Feb 29;806(Pt 3):151298. Epub 2021 Oct 29.

BIC-ESAT and SKL-ESPC, College of Environmental Sciences and Engineering, Peking University, Beijing, China. Electronic address:

Background: Emerging evidence suggests that biological intermediates play an important role in initiating fine particulate matter (PM)-associated prohypertensive pathways, but sensitive biomarkers for this pathway are lacking.

Aim: To explore whether short-term exposure to PM is associated with the concentration of 20-hydroxyeicosatetraenoic acid (20-HETE), a potent vasoactive lipid relevant to the pathophysiology of hypertension.

Methods: In this longitudinal panel study, we repeatedly (up to seven times) measured the blood concentrations of 20-HETE in 120 adults living in Beijing, China. Ambient exposure metrics included the concentrations of hourly PM mass and daily PM constituents, including three carbonaceous components, eight water-soluble ions, and 16 trace elements. Linear mixed-effects models were used to examine the associations between the change in the 20-HETE concentration and short-term exposure to ambient PM metrics after adjustment for age, sex, body mass index, behavioral exposure, socioeconomic characteristics, and meteorological factors.

Results: The interquartile range (IQR) increase in the 7-15-hour-lag exposure to PM (80 μg/m) was associated significantly with a 5.3% (95% confidence interval [CI], 0.1-10.7%) to 6.5% (95% CI, 1.7-11.6%) increase in the blood concentration of 20-HETE. The magnitude of the association differed by age, sex, prediabetic status, obesity, and hypertensive status, with a significantly greater increase in 20-HETE observed among those with fasting plasma glucose concentrations ≥ 6.1 mmol/L. In addition to the PM mass, the 20-HETE concentration was associated consistently with IQR increases in the 1-day lag exposure to organic carbon (5.7%), black carbon (9.5%), nitrate (3.9%), chloride (2.9%), copper (5.5%), zinc (4.7%), barium (4.1%), and lead (6.2%). The organic carbon estimate was robust in the two-pollutant models. Furthermore, increased 20-HETE correlated with elevated blood pressure (BP), although no mediation of 20-HETE on PM-associated BP change was found.

Conclusions: The 20-HETE blood concentration increased significantly in response to short-term exposure to ambient PM, which may be partly responsible for the prohypertensive effects of PM.
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http://dx.doi.org/10.1016/j.scitotenv.2021.151298DOI Listing
February 2022

Facile Synthesis of Amorphous MoCo Lamellar Hydroxide for Alkaline Water Oxidation.

ChemSusChem 2021 Nov 5. Epub 2021 Nov 5.

School of Materials Science and Engineering, Beihang University, 100191, Beijing, P. R. China.

To find an oxygen evolution reaction (OER) catalyst with satisfactory catalytic performance and affordable cost is of great importance to the development of many new energy devices. In this work, a simple and effective strategy was developed to synthesize a series of amorphous MoCo lamellar hydroxide through one-step chemical co-precipitation. Systematic investigations showed that different functional agents (2-methylimidazole, NaOH, NH OH) in the fabrication process resulted in different micromorphology of the catalyst, thus influencing its electrocatalytic performance. Also, adding various amounts of Mo could influence the intrinsic catalytic properties. Samples synthesized with appropriate functional agent addition and optimized Mo addition exhibited amorphous nature and bent nanosheet morphology, as well as highest intrinsic catalytic activity, showing a low overpotential of 290 mV at 10 mA cm and a small Tafel slope of 55 mV dec in 1 m KOH solution. Additionally, the catalytic performance of the sample showed just small decay after 50 h chronopotentiometry test and 3000 cyclic voltammetry cycles, exhibiting the ultra-stable catalytic activity of the catalyst. This work provides a possible large-scale commercial production strategy of OER catalysts with promising performance and low fabrication cost.
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http://dx.doi.org/10.1002/cssc.202101666DOI Listing
November 2021

Metabolic Molecule PLA2G2D Is a Potential Prognostic Biomarker Correlating With Immune Cell Infiltration and the Expression of Immune Checkpoint Genes in Cervical Squamous Cell Carcinoma.

Front Oncol 2021 18;11:755668. Epub 2021 Oct 18.

Cancer Biology Research Center (Key Laboratory of the Ministry of Education), Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Cervical squamous cell carcinoma (CSCC) is the major pathological type of cervical cancer (CC), the second most prevalent reproductive system malignant tumor threatening the health of women worldwide. The prognosis of CSCC patients is largely affected by the tumor immune microenvironment (TIME); however, the biomarker landscape related to the immune microenvironment of CSCC and patient prognosis is less characterized. Here, we analyzed RNA-seq data of CSCC patients from The Cancer Genome Atlas (TCGA) database by dividing it into high- and low-immune infiltration groups with the MCP-counter and ESTIMATE R packages. After combining weighted gene co-expression network analysis (WGCNA) and differentially expressed gene (DEG) analysis, we found that , a metabolism-associated gene, is the top gene positively associated with immune infiltration and patient survival. This finding was validated using data from The Cancer Genome Characterization Initiative (CGCI) database and further confirmed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, multiplex immunohistochemistry (mIHC) was performed to confirm the differential infiltration of immune cells between -high and -low tumors at the protein level. Our results demonstrated that expression was significantly correlated with the infiltration of immune cells, especially T cells and macrophages. More importantly, -high tumors also exhibited higher infiltration of CD8 T cells inside the tumor region than -low tumors. In addition, PLA2G2D expression was found to be positively correlated with the expression of multiple immune checkpoint genes (ICPs). Moreover, based on other immunotherapy cohort data, high expression is correlated with increased cytotoxicity and favorable response to immune checkpoint blockade (ICB) therapy. Hence, PLA2G2D could be a novel potential biomarker for immune cell infiltration, patient survival, and the response to ICB therapy in CSCC and may represent a promising target for the treatment of CSCC patients.
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http://dx.doi.org/10.3389/fonc.2021.755668DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8558485PMC
October 2021

Synthetic digital reconstructed radiographs for MR-only robotic stereotactic radiation therapy: A proof of concept.

Comput Biol Med 2021 11 4;138:104917. Epub 2021 Oct 4.

Department of Radiation Oncology, University of North Carolina, Chapel Hill, NC, USA. Electronic address:

Purpose: To create synthetic CTs and digital reconstructed radiographs (DRRs) from MR images that allow for fiducial visualization and accurate dose calculation for MR-only radiosurgery.

Methods: We developed a machine learning model to create synthetic CTs from pelvic MRs for prostate treatments. This model has been previously proven to generate synthetic CTs with accuracy on par or better than alternate methods, such as atlas-based registration. Our dataset consisted of 11 paired CT and conventional MR (T2) images used for previous CyberKnife (Accuray, Inc) radiotherapy treatments. The MR images were pre-processed to mimic the appearance of fiducial-enhancing images. Two models were trained for each parameter case, using a sub-set of the available image pairs, with the remaining images set aside for testing and validation of the model to identify the optimal patch size and number of image pairs used for training. Four models were then trained using the identified parameters and used to generate synthetic CTs, which in turn were used to generate DRRs at angles 45° and 315°, as would be used for a CyberKnife treatment. The synthetic CTs and DRRs were compared visually and using the mean squared error and peak signal-to-noise ratio against the ground-truth images to evaluate their similarity.

Results: The synthetic CTs, as well as the DRRs generated from them, gave similar visualization of the fiducial markers in the prostate as the true counterparts. There was no significant difference found for the fiducial localization for the CTs and DRRs. Across the 8 DRRs analyzed, the mean MSE between the normalized true and synthetic DRRs was 0.66 ± 0.42% and the mean PSNR for this region was 22.9 ± 3.7 dB. For the full CTs, the mean MAE was 72.9 ± 88.1 HU and the mean PSNR was 31.2 ± 2.2 dB.

Conclusions: Our machine learning-based method provides a proof of concept of a way to generate synthetic CTs and DRRs for accurate dose calculation and fiducial localization for use in radiation treatment of the prostate.
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http://dx.doi.org/10.1016/j.compbiomed.2021.104917DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8627784PMC
November 2021

Detection of HPV and Human Chromosome Sites by Dual-Color Fluorescence Hybridization Reveals Recurrent HPV Integration Sites and Heterogeneity in Cervical Cancer.

Front Oncol 2021 5;11:734758. Epub 2021 Oct 5.

Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Human papillomavirus (HPV) integration in the human genome is suggested to be an important cause of cervical cancer. With the development of sequencing technologies, an increasing number of integration "hotspots" have been identified. However, this HPV integration information was derived from analysis of whole cervical cancer tissue, and we know very little about the integration in different cancer cell subgroups or individual cancer cells. This study optimized the preparation of probes and provided a dual-color fluorescence hybridization (FISH) method to detect HPV integration sites in paraffin-embedded cervical cancer samples. We used both HPV probes and site-specific probes: 3p14 (), 8q24 (), 13q22 (/), 3q28 (), and 5p15 (). We detected HPV signals in 75 of the 96 cases of cervical cancer; 62 cases showed punctate signals, and 13 cases showed diffuse punctate signals. We identified 3p14 as a high-frequency HPV integration site in 4 cervical cancer cases. HPV integration at 8p14 occurred in 2 cases of cervical cancer. In the same cervical cancer tissue of sample No.1321, two distinct subgroups of cells were observed based on the HPV probe but showed no difference in cell and nucleus morphology. Our study provides a new method to investigate the frequent HPV integration sites in cervical cancer and reports the heterogeneity within cervical cancer from the perspective of HPV integration.
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http://dx.doi.org/10.3389/fonc.2021.734758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8523950PMC
October 2021

Metagenomic next-generation sequencing (mNGS) confirmed a critical case of severe fever with thrombocytopenia syndrome virus (SFTSV).

Clin Chem Lab Med 2021 Oct 22. Epub 2021 Oct 22.

Department of Infectious Disease, Shanghai Changhai Hospital, Navi Medical University, Shanghai, P.R. China.

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http://dx.doi.org/10.1515/cclm-2021-0791DOI Listing
October 2021

Microcirculation of intramyocardial hemorrhage caused by reperfused myocardial infarctions with ultrasmall superparamagnetic iron oxide cardiac magnetic resonance imaging.

Acta Radiol 2021 Oct 20:2841851211046332. Epub 2021 Oct 20.

Department of Radiology, West China Hospital, 535104Sichuan University, Chengdu, PR China.

Background: The actual role of the coronary microcirculation, which is massively injured by myocardial infarction (MI), in intramyocardial hemorrhage (IMH) pathophysiology is still not fully understood.

Purpose: To determine the change and distribution of microcirculation of myocardial edema (ME), IMH, MI, and the remote area of early reperfusion using 7.0-T cardiovascular magnetic resonance (CMR) in a rat model of acute MI.

Material And Methods: Eight rats with 60-min myocardial ischemia followed by reperfusion were investigated. On days 2 and 7, after the acquisition of T2*-mapping and T2-mapping images, late gadolinium enhancement imaging was performed to evaluate the extent of myocardial ischemia after an injection of Gd-DTPA. On days 3 and 8, after the injection of ultrasmall superparamagnetic iron oxide (USPIO), T2*- and T2-mapping images were acquired. The R2 values of ME, IMH, MI, and remote areas were measured.

Results: From days 2 to 3, R2 values increased in the IMH, MI, ME, and remote area (all < 0.05) following administration of USPIO, while the delta R2 value of IMH and MI was larger than remote area (< 0.05). From day 7 to day 8, there was no significant difference in the IMH, MI, ME, and remote area (all > 0.05).

Conclusion: Microvascular injury of IMH and MI is the most severe among all the studied myocardial injuries in the early reperfusion of MI, while microvascular density decreased during follow-up.
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http://dx.doi.org/10.1177/02841851211046332DOI Listing
October 2021

[Developmental characteristics of biological soil crusts and their effects on soil water infiltration on karst slope].

Ying Yong Sheng Tai Xue Bao 2021 Aug;32(8):2875-2885

Faculty of Geographical Science, Beijing Normal University, Beijing 100875, China.

Biological soil crusts (BSCs), as a pioneer for vegetation restoration and crucial component of surface landscape, greatly affect land surface process. To explore the development of BSCs and its effects on soil water infiltration in karst region, we investigated the development of BSCs and analyzed the infiltration processes with different BSCs coverages (0, 28%, 40%, 70%, 97%) and rainfall intensities (42 and 132 mm·h) in simulating rainfall experiments on a typical karst slope. The results showed that there were significant differences in the development of BSCs for different land use types, whereas the spatial variation of BSCs development on the slope was not obvious under the same land use type. Compared to the bare plot, the presence of BSCs significantly increased surface roughness, the initial runoff generation time, and soil water infiltration. In the cases of light (42 mm·h) and intensive (132 mm·h) rainfall, the initial infiltration rate of BSCs covered plots were 1.7-1.9 times and 1.2-1.9 times as that of bare plot, while the average infiltration rate in BSCs covered plots were 2.5-3.0 times and 1.4-3.3 times as that of bare plot, respectively. The BSCs coverage was significantly positively correlated with the initial runoff production time. The critical values of facilitating infiltration of BSCs coverage were between 65% and 70% under the test rainfall intensities. For heavy rainfall events, the inhibiting effects of BSCs on surface runoff were weakened. Horton model was the most reliable one for describing the infiltration process on karst slope with BSCs, followed by Kostiakov model and Philip model. In conclusion, the spatial variability of BSCs development on the karst slope was higher. The presence of BSCs had a significant effect on soil permeability in karst region.
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http://dx.doi.org/10.13287/j.1001-9332.202108.011DOI Listing
August 2021

Identification and Evaluation of Wheat-Aegilops bicornis Lines with Resistance to Powdery Mildew and Stripe Rust.

Plant Dis 2021 Oct 13. Epub 2021 Oct 13.

Crop Research Institute, 56644, Shandong Academy of Agricultural Sciences, 202 Gongyebei Road, Jinan, Shandong, China, Jinan, Shandong, China, 250100;

Wheat pathogens, especially those causing powdery mildew and stripe rust, seriously threaten yield worldwide. Utilizing newly identified disease resistance genes from wheat relatives is an effective strategy to minimize disease damage. In this study, chromosome-specific molecular markers for the 3Sb and 7Sb chromosomes of Aegilops bicornis were developed using PCR-based landmark unique gene (PLUG) primers for screening wheat-Ae. bicornis progenies. Fluorescence in situ hybridization (FISH) was performed to further identify wheat-Ae. bicornis progenies using oligonucleotides probes Oligo-pSc119.2-1, Oligo-pTa535-1, and Oligo-(GAA)8. After establishing Ae. bicornis 3Sb and 7Sb chromosome-specific FISH markers, Holdfast (common wheat)-Ae. bicornis 3Sb addition, 7Sb addition, 3Sb(3A) substitution, 3Sb(3B) substitution, 3Sb(3D) substitution, 7Sb(7A) substitution, and 7Sb(7B) substitution lines were identified by the molecular and cytological markers. Stripe rust and powdery mildew resistance, along with agronomic traits were investigated to evaluate the breeding potential of these lines. Holdfast and Holdfast-Ae. bicornis progenies were all highly resistant to stripe rust, indicating that the stripe rust resistance might derive from Holdfast. However, Holdfast-Ae. bicornis 3Sb addition, 3Sb(3A) substitution, 3Sb(3B) substitution, and 3Sb(3D) substitution lines showed high resistance to powdery mildew while Holdfast was highly susceptible, indicating that chromosome 3Sb of Ae. bicornis carries previously unknown powdery mildew resistance gene(s). Additionally, the transfer of the 3Sb chromosome from Ae. bicornis to wheat significantly increased tiller number, but chromosome 7Sb has a negative effect on agronomic traits. Therefore, wheat germplasm containing Ae. bicornis chromosome 3Sb has potential to contribute to improving powdery mildew resistance and tiller number during wheat breeding.
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http://dx.doi.org/10.1094/PDIS-05-21-0982-REDOI Listing
October 2021

Ethylene-induced NbMYB4L is involved in resistance against tobacco mosaic virus in Nicotiana benthamiana.

Mol Plant Pathol 2021 Oct 11. Epub 2021 Oct 11.

College of Life Science, Yantai University, Yantai, China.

Several MYB transcription factors are known to play important roles in plant resistance to environmental stressors. However, the mechanism governing the involvement of MYBs in regulating tobacco mosaic virus (TMV) resistance in plants is still unclear. In this study, we found that not only is Nicotiana benthamiana MYB4-like involved in defence against TMV, but also that the ethylene pathway participates in MYB4L-mediated resistance. Transcription of NbMYB4L was up-regulated in N. benthamiana infected with TMV. Silencing of NbMYB4L led to intensified TMV replication, whereas overexpression of NbMYB4L induced significant resistance to TMV. Transcription of NbMYB4L was greater in 1-aminocyclopropanecarboxylic acid (ACC, ethylene precursor)-pretreated plants but lower when the ethylene signalling pathway was blocked during TMV infection. Gene expression analysis showed that the transcription of NbMYB4L was largely suppressed in ETHYLENE INSENSITIVE 3-like 1(EIL1)-silenced plants. The results of electrophoretic mobility shift assay and chromatin immunoprecipitation-quantitative PCR (ChIP-qPCR) experiments indicated that NbEIL1 could directly bind to two specific regions of the NbMYB4L promoter. Furthermore, a luciferase assay revealed that NbEIL1 significantly induced the reporter activity of the MYB4L promoter in N. benthamiana. These results point to NbEIL1 functioning as a positive regulator of NbMYB4L transcription in N. benthamiana against TMV. Collectively, our work reveals that EIL1 and MYB4L constitute a coherent feed-forward loop involved in the robust regulation of resistance to TMV in N. benthamiana.
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http://dx.doi.org/10.1111/mpp.13139DOI Listing
October 2021

Technical overview of magnetic resonance fingerprinting and its applications in radiation therapy.

Med Phys 2021 Oct 11. Epub 2021 Oct 11.

Department of Biomedical Engineering, Case Western Reserve University, Cleveland, Ohio, USA.

Magnetic resonance fingerprinting (MRF) is an emerging imaging technique for rapid and simultaneous quantification of multiple tissue properties. The technique has been developed for quantitative imaging of different organs. The obtained quantitative measures have the potential to improve multiple steps of a typical radiotherapy workflow and potentially further improve integration of magnetic resonance imaging guided clinical decision making. In this review paper, we first provide a technical overview of the MRF method from data acquisition to postprocessing, along with recent development in advanced reconstruction methods. We further discuss critical aspects that could influence its usage in radiation therapy, such as accuracy and precision, repeatability and reproducibility, geometric distortion, and motion robustness. Finally, future directions for MRF application in radiation therapy are discussed.
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http://dx.doi.org/10.1002/mp.15254DOI Listing
October 2021

Thiophene- and selenophene-based conjugated polymeric mixed ionic/electronic conductors.

J Chem Phys 2021 Oct;155(13):134704

Department of Chemistry, University of Toronto, 80 St. George Street, Toronto, Ontario, M5S 3H6, Canada.

Mixed ionic/electronic conductors (MIECs) are desirable materials for next-generation electronic devices and energy storage applications. Polymeric MIECs are attractive from the standpoint that their structure can be controlled and anticipated to have mechanically robust properties. Here, we prepare and investigate conjugated copolymers containing thiophene and selenophene repeat units and their homopolymer counterparts. Specifically, thiophene bearing a triethylene glycol (EG) side chain was polymerized and copolymerized with dodecyl thiophene/selenophene monomers. The synthesis leads to a class of copolymers that contain either S or Se and are blocky in nature. The Li-ion conductivity of ionically doped copolymers, P3DDT-s-P3(EG)T and P3DDS-s-P3(EG)T (9.7 × 10 and 8.2 × 10 S/cm, respectively), was 3-4 fold higher than that of the ionically doped constituent homopolymer, P3(EG)T (2.2 × 10 S/cm), at ambient conditions. The electronic conductivity of the oxidatively doped copolymers was significantly higher than that of the constituent homopolymer P3(EG)T, and most notably, P3DDS-s-P3(EG)T reached ∼7 S/cm, which is the same order of magnitude as poly(3-dodecylthiophene) and poly(3-dodecylselenophene), which are the highest oxidatively doped conductors based on control experiments. Our findings provide implications for designing new MIECs based on copolymerization and the incorporation of heavy atom heterocycles.
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http://dx.doi.org/10.1063/5.0064858DOI Listing
October 2021

Chemical Production of Oxygenated Volatile Organic Compounds Strongly Enhances Boundary-Layer Oxidation Chemistry and Ozone Production.

Environ Sci Technol 2021 10 8;55(20):13718-13727. Epub 2021 Oct 8.

State Key Joint Laboratory of Environmental Simulation and Pollution Control, College of Environmental Sciences and Engineering, Peking University, Beijing 100871, China.

Photolysis of oxygenated volatile organic compounds (OVOCs) produces a primary source of free radicals, including OH and inorganic and organic peroxy radicals (HO and RO), consequently increasing photochemical ozone production. The amplification of radical cycling through OVOC photolysis provides an important positive feedback mechanism to accelerate ozone production. The large production of OVOCs near the surface helps promote photochemistry in the whole boundary layer. This amplifier effect is most significant in regions with high nitrogen oxides (NO) and VOC concentrations such as Wangdu, China. Using a 1-D model with comprehensive observations at Wangdu and the Master Chemical Mechanism (MCM), we find that OVOC photolysis is the largest free-radical source in the boundary layer (46%). The condensed chemistry mechanism we used severely underestimates the OVOC amplifier effect in the boundary layer, resulting in a lower ozone production rate sensitivity to NO emissions. Due to this underestimation, the model-simulated threshold NO emission value, below which ozone production decreases with NO emission decrease, is biased low by 24%. The underestimated OVOC amplifier effect in a condensed mechanism implies a low bias in the current 3-D model-estimated efficacy of NO emission reduction on controlling ozone in polluted urban and suburban regions of China.
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http://dx.doi.org/10.1021/acs.est.1c04489DOI Listing
October 2021

Parthenolide promotes the repair of spinal cord injury by modulating M1/M2 polarization via the NF-κB and STAT 1/3 signaling pathway.

Cell Death Discov 2020 Oct 6;6(1):97. Epub 2020 Oct 6.

Department of Orthopedic, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Spinal cord injury (SCI) is a severe neurological disease; however, there is no effective treatment for spinal cord injury. Neuroinflammation involves the activation of resident microglia and the infiltration of macrophages is the major pathogenesis of SCI secondary injury and considered to be the therapeutic target of SCI. Parthenolide (PN) has been reported to exert anti-inflammatory effects in fever, migraines, arthritis, and superficial inflammation; however, the role of PN in SCI therapeutics has not been clarified. In this study, we showed that PN could improve the functional recovery of spinal cord in mice as revealed by increased BMS scores and decreased cavity of spinal cord injury in vivo. Immunofluorescence staining experiments confirmed that PN could promote axonal regeneration, increase myelin reconstitution, reduce chondroitin sulfate formation, inhibit scar hyperplasia, suppress the activation of A1 neurotoxic reactive astrocytes and facilitate shift from M1 to M2 polarization of microglia/macrophages. To verify how PN exerts its effects on microglia/macrophages polarization, we performed the mechanism study in vitro in microglia cell line BV-2. PN could significantly reduce M1 polarization in BV2 cells and partially rescue the decrease in the expression of M2 phenotype markers of microglia/macrophage induced by LPS, but no significant effect on M2 polarization stimulated with IL-4 was observed. Further study demonstrated PN inhibited NF-κB signal pathway directly or indirectly, and suppressed activation of signal transducer and activator of transcription 1 or 3 (STAT1/3) via reducing the expression of HDAC1 and subsequently increasing the levels of STAT1/3 acetylation. Overall, our study illustrated that PN may be a promising strategy for traumatic SCI.
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http://dx.doi.org/10.1038/s41420-020-00333-8DOI Listing
October 2020

Highly differential count of circulating and tumor infiltrating immune cells in patients with non-HCV/non-HBV hepatocellular carcinoma.

Cancer Immunol Immunother 2021 Sep 28. Epub 2021 Sep 28.

Department of General, Visceral, and Transplant Surgery, Ludwig-Maximilians-University Munich, Marchioninistraße 15, 81377, Munich, Germany.

Background: Liver transplantation and liver resection are curative options for early hepatocellular carcinoma (HCC). The outcome is in part depended on the immunological response to the malignancy. In this study, we aimed to identify immunological profiles of non-HCV/non-HBV HCC patients.

Methods: Thirty-nine immune cell subsets were measured with multicolor flow cytometry. This immunophenotyping was performed in peripheral blood (PB) and tumor specimens of 10 HCC resection patients and 10 healthy donors. The signatures of the highly differential leukocyte count (hDIF) were analyzed using multidimensional techniques. Functional capability was measured using intracellular IFN-γ staining (Trial Registration DRKS00013567).

Results: The hDIF showed activation (subsets of T-, B-, NK- and dendritic cells) and suppression (subsets of myeloid-derived suppressor cells and T- and B-regulatory cells) of the antitumor response. Principal component analysis of PB and tumor infiltrating leukocytes (TIL) illustrated an antitumor activating gradient. TILs showed functional capability by secreting IFN-γ but did not kill HCC cells.

Conclusions: In conclusion, the measurement of the hDIF shows distinct differences in immune reactions against non-HBV/non-HCV HCC and illustrates an immunosuppressive gradient toward peripheral blood.

Trial Registration: DRKS00013567.
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http://dx.doi.org/10.1007/s00262-021-03061-9DOI Listing
September 2021

An L1 retrotransposon insertion-induced deafness mouse model for studying the development and function of the cochlear stria vascularis.

Proc Natl Acad Sci U S A 2021 10;118(40)

School of Life Sciences, Tsinghua University, Beijing, China 100084;

Dysregulation of ion and potential homeostasis in the scala media is the most prevalent cause of hearing loss in mammals. However, it is not well understood how the development and function of the stria vascularis regulates this fluid homeostasis in the scala media. From a mouse genetic screen, we characterize a mouse line, named , that displays profound hearing impairment. Histology suggests that mutant mice carry a severe, congenital structural defect of the stria vascularis. The in vivo recording of mice using double-barreled electrodes shows that endocochlear potential is abolished and potassium concentration is reduced to ∼20 mM in the scala media, a stark contrast to the +80 mV endocochlear potential and the 150 mM potassium concentration present in healthy control mice. Genomic analysis revealed a roughly 7-kb-long, interspersed nuclear element (LINE-1 or L1) retrotransposon insertion on chromosome 11. Strikingly, the deletion of this L1 retrotransposon insertion from chromosome 11 restored the hearing of mutant mice. In summary, we characterize a mouse model that enables the study of stria vascularis development and fluid homeostasis in the scala media.
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http://dx.doi.org/10.1073/pnas.2107933118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501756PMC
October 2021

Bright and Stable Light-Emitting Diodes Based on Perovskite Quantum Dots in Perovskite Matrix.

J Am Chem Soc 2021 Sep 20;143(38):15606-15615. Epub 2021 Sep 20.

Department of Electrical and Computer Engineering, University of Toronto, 35 St. George Street, Toronto, Ontario M5S 1A4, Canada.

Light-emitting diodes (LEDs) based on metal halide perovskite quantum dots (QDs) have achieved impressive external quantum efficiencies; however, the lack of surface protection of QDs, combined with efficiency droop, decreases device operating lifetime at brightnesses of interest. The epitaxial incorporation of QDs within a semiconducting shell provides surface passivation and exciton confinement. Achieving this goal in the case of perovskite QDs remains an unsolved challenge in view of the materials' chemical instability. Here, we report perovskite QDs that remain stable in a thin layer of precursor solution of perovskite, and we use strained QDs as nucleation centers to drive the homogeneous crystallization of a perovskite matrix. Type-I band alignment ensures that the QDs are charge acceptors and radiative emitters. The new materials show suppressed Auger bi-excition recombination and bright luminescence at high excitation (600 W cm), whereas control materials exhibit severe bleaching. Primary red LEDs based on the new materials show an external quantum efficiency of 18%, and these retain high performance to brightnesses exceeding 4700 cd m. The new materials enable LEDs having an operating half-life of 2400 h at an initial luminance of 100 cd m, representing a 100-fold enhancement relative to the best primary red perovskite LEDs.
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http://dx.doi.org/10.1021/jacs.1c02148DOI Listing
September 2021

Serum branched-chain amino acids modifies the associations between air pollutants and insulin resistance.

Ecotoxicol Environ Saf 2021 Dec 16;225:112780. Epub 2021 Sep 16.

State Key Joint Laboratory of Environmental Simulation and Pollution Control, International Joint Laboratory for Regional Pollution Control (IJRC), Ministry of Education, College of Environmental Sciences and Engineering, Beijing 100871, China. Electronic address:

Growing evidence supports that air pollution exposure has become a risk factor of type II diabetes mellitus through the induction of insulin resistance (IR), but the presented findings did not provide a consistent relationship between air pollution exposure and IR in the temporal scale and the magnitude. Reported associated with IR and air pollution exposure, branched-chain amino acids (BCAAs) in blood might modify the association between air pollution exposure and IR. We took advantage of an existing panel study on elderly people who were healthy or with pre-diabetes. Amino acids were analyzed from the serum samples using a UPLC-QQQ-MS, and the homeostasis model assessment of insulin resistance (HOMA-IR) values were calculated to represent the levels of IR in each visit. Exposures to PM, NO, SO, CO, O, and black carbon (BC) were estimated using data from a monitoring station. Linear mixed-effects models were applied to estimate the associations between the air pollution and HOMA-IR, as well as the modifying effects of BCAAs. We found significantly higher concentrations of BCAAs in the pre-diabetic subjects than healthy ones. The concentrations of BCAAs were all significantly associated with HOMA-IR. For subjects with high-level BCAAs, HOMA-IR was positively associated with an IQR increase in PM, NO, BC, and CO at lag day 2 and in PM, SO, NO, BC, and CO at lag day 7. While for subjects with low-level BCAAs, there was no significant association observed at any lag day except for CO at lag day 5. The study provided evidence that circulating BCAAs may modify the relationship between air pollution exposure and the level of insulin resistance in humans.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112780DOI Listing
December 2021
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