Publications by authors named "Haoyu Zhang"

52 Publications

Development and validation of multiple machine learning algorithms for the classification of G-protein-coupled receptors using molecular evolution model-based feature extraction strategy.

Amino Acids 2021 Sep 25. Epub 2021 Sep 25.

School of Information Engineering, Zhejiang Ocean University, Zhoushan, China.

Machine learning is one of the most potential ways to realize the function prediction of the incremental large-scale G-protein-coupled receptors (GPCR). Prior research reveals that the key to determining the overall classification accuracy of GPCR is extracting valuable features and filtering out redundancy. To achieve a more efficient classification model, we put the feature synonym problem into consideration and create a new method based on functional word clustering and integration. Through evaluating the evolution correlation between features using the transition scores in mature molecular substitution matrices, candidate features are clustered into synonym groups. Each group of the clustered features is then integrated and represented by a unique key functional word. These retained key functional words are used to form a feature knowledge base. The original GPCR sequences are then transferred into feature vectors based on a feature re-extraction strategy according to the features in the knowledge base before the training and testing stage. We create multiple machine learning models based on Naïve Bayesian (NB), random forest (RF), support vector machine (SVM), and multi-layer perceptron (MLP) algorithms. The established model is applied to classify two public data sets containing 8354 and 12,731 GPCRs, respectively. These models achieve significant performance in almost all evaluation criteria in comparison with state-of-the art. This work demonstrated the potential of the novel feature extraction strategy and provided an effective theoretical design for the hierarchical classification of GPCRs.
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http://dx.doi.org/10.1007/s00726-021-03080-xDOI Listing
September 2021

Biomimetic Synthesis of Natural Products: A Journey To Learn, To Mimic, and To Be Better.

Acc Chem Res 2021 10 22;54(19):3720-3733. Epub 2021 Sep 22.

School of Pharmaceutical Sciences, MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Tsinghua University, Beijing 100084, China.

Total synthesis of natural products has been one of the most exciting and dynamic areas in synthetic organic chemistry. Nowadays, the major challenge in this field is not whether a given target of interest can be synthesized but how to make it with commendable efficiency and practicality. To meet this grand challenge, a wise way is to learn from Mother Nature who is recognized for her superb capability of forging complicated and sometimes beyond-imagination molecules in her own delicate way. Indeed, since Sir Robert Robinson published his groundbreaking synthesis of tropinone in 1917, biomimetic synthesis of natural products, a process of imitating nature's way to make molecules, has evolved into one of the most popular research directions in organic synthesis.Our group has been engaging in biomimetic synthesis of natural products in the past decade. During this time, we have come to realize that the successful implementation of a biomimetic synthesis entails the orchestrated combination of bioinspiration and rational design. On the one hand, we prefer to utilize some elegant bioinspired transformations (e.g., Diels-Alder dimerization, 6π-electrocyclization, and [2 + 2]-photocycloaddition) as the key steps of our synthesis, which enable rapid construction of the core skeletons of the chased targets with high efficiency; on the other hand, various powerful reactions (e.g., dyotropic rearrangement of β-lactone, tandem aldol condensation/Grob fragmentation reaction, and organocatalytic asymmetric Mukaiyama-Michael addition) are rationally designed by us, which allow for facile access to the requisite precursors for attempting biomimetic transformations. In some cases, the proposed biomimetic transformation may fail to give a satisfactory result in practice, and thus we opt to develop creative tactics (e.g., hydrogen atom transfer-triggered vinyl cyclobutane ring opening/oxygen insertion/cyclization cascade) that can meet the challenge. Guided by this synthesis concept, we have achieved the total syntheses of multiple families of natural products of great importance in both chemistry and biology, representatives of which include xanthanolides, cytochalasans, and plakortin-type polyketides. Of note, most of these targets could be accessed in a concise, efficient, and scalable manner, which paves the way for further exploration of their biological functions and medicinal potential. Moreover, owing to their biomimetic nature, our syntheses provide valuable information for deciphering the underlying biosynthetic pathways of the chased targets, which could not be attained by other synthetic modes.
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http://dx.doi.org/10.1021/acs.accounts.1c00459DOI Listing
October 2021

Orthogonal genome-wide screens of bat cells identify MTHFD1 as a target of broad antiviral therapy.

Proc Natl Acad Sci U S A 2021 09;118(39)

MOE Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology, Beijing Advanced Innovation Center for Structural Biology, School of Pharmaceutical Sciences, Tsinghua-Peking Center for Life Sciences, Center for Infectious Disease Research, School of Medicine, Tsinghua University, 100084 Beijing, China;

Bats are responsible for the zoonotic transmission of several major viral diseases, including those leading to the 2003 SARS outbreak and likely the ongoing COVID-19 pandemic. While comparative genomics studies have revealed characteristic adaptations of the bat innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the viral tolerance in bats. Here we report the establishment of genome-wide RNA interference (RNAi) and CRISPR libraries for the screening of the model megabat, We used the complementary RNAi and CRISPR libraries to interrogate cells for infection with two different viruses: mumps virus and influenza A virus, respectively. Independent screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells and human cells. The MTHFD1 inhibitor, carolacton, potently blocked replication of several RNA viruses, including SARS-CoV-2. We also discovered that bats have lower expression levels of MTHFD1 than humans. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad-spectrum antiviral therapy.
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http://dx.doi.org/10.1073/pnas.2104759118DOI Listing
September 2021

Withdrawal of Colistin Reduces Incidence of -Harboring IncX4-Type Plasmids but Has Limited Effects on Unrelated Antibiotic Resistance.

Pathogens 2021 Aug 12;10(8). Epub 2021 Aug 12.

Animal Disease Prevention and Food Safety Key Laboratory of Sichuan Province, Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610065, China.

The global dissemination of plasmid-mediated colistin resistance gene and its variants have posed a great threat to public health. Therefore, the Chinese government banned the use of colistin as a feed additive in livestock in April 2017. To explore the dynamic changes of overall antibiotic resistance genes (ARGs) and phylogenetic relationship of bacteria from a single pig farm before and after the withdrawal of colistin, fecal swab samples were collected from a large-scale pig farm before ( = 32; 2 months pre-withdrawal of colistin) and after withdrawal of colistin ( = 30; 13 months post-withdrawal of colistin). and were isolated. Whole-genome sequencing (Illumina, MiSeq) was performed to examine ARGs, plasmids and the genetic relationship of the isolates. The overall SNP results indicated all isolates had high genetic diversity, and the evolutionary relationship across isolates was not influenced by the ban of colistin. However, the prevalence of (5.6%, < 0.01) was significantly lower than before the ban (86.4%). Plasmid profiling analysis showed that 17 of 20 (85.0%) observed genes reside on IncX4-type plasmids, 16 of which (94.1%) were from isolates before the ban. On the contrary, the presence of gene was significantly increased ( = 0.0215) post-withdrawal of colistin. Our results showed that withdrawal of colistin reduced the incidence of -harboring IncX4-type plasmids, but had limited influences on unrelated ARGs.
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http://dx.doi.org/10.3390/pathogens10081019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8398929PMC
August 2021

Highly sensitive self-healable strain biosensors based on robust transparent conductive nanocellulose nanocomposites: Relationship between percolated network and sensing mechanism.

Biosens Bioelectron 2021 Nov 29;191:113467. Epub 2021 Jun 29.

Department of Chemical Engineering, Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario, Canada. Electronic address:

The conventional skin sensor detection of human physiological signals can be an effective method for disease diagnosis and health monitoring, but the poor biocompatibility, low sensitivity and complex design largely limit their applications. Developing natural nanofiller-reinforced composites as strain biosensors is an appealing solution to reduce environmental impacts and overcome technical bottleneck. Herein, a versatile nature skin-inspired composite film as flexible strain biosensor was developed based on cellulose nanocrystals-polyaniline (CNC-PANI) composites by utilizing their percolated conductive network in polyvinyl alcohol (PVA) matrix. The composite electronic skin showed robust mechanical strength (50.62 MPa) and high sensitivity (Gauge Factor = 11.467) with easy water-induced self-healing abilities. Moreover, we investigated the functioning mechanism of percolated network and the sensory behavior determined by CNC nanocomposite alignment. The percolation threshold of CNC-polyaniline (PANI) was determined at 4.278% and 5% CNC-PANI composite film shows the best overall sensing property. It was also discovered that the sensitivity of this type of conductive-filler electronic skin can be divided into two separate regions at different strain range due to its percolated network. With films prepared by dry casting and dip coating, the alignment of CNC-PANI also contributes to this unique change in electrical property. Generally, our results demonstrated the mechanism and tunability of conductive nanofiller-based composite strain biosensors as a potential alternative to commercial synthetic sensors.
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http://dx.doi.org/10.1016/j.bios.2021.113467DOI Listing
November 2021

AZD8055 enhances in vivo efficacy of afatinib in chordomas.

J Pathol 2021 Sep 28;255(1):72-83. Epub 2021 Jul 28.

Department of Neurosurgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Chordomas are primary bone tumors that arise in the cranial base, mobile spine, and sacrococcygeal region, affecting patients of all ages. Currently, there are no approved agents for chordoma patients. Here, we evaluated the anti-tumor efficacy of small molecule inhibitors that target oncogenic pathways in chordoma, as single agents and in combination, to identify novel therapeutic approaches with the greatest translational potential. A panel of small molecule compounds was screened in vivo against patient-derived xenograft (PDX) models of chordoma, and potentially synergistic combinations were further evaluated using chordoma cell lines and xenograft models. Among the tested agents, inhibitors of EGFR (BIBX 1382, erlotinib, and afatinib), c-MET (crizotinib), and mTOR (AZD8055) significantly inhibited tumor growth in vivo but did not induce tumor regression. Co-inhibition of EGFR and c-MET using erlotinib and crizotinib synergistically reduced cell viability in chordoma cell lines but did not result in enhanced in vivo activity. Co-inhibition of EGFR and mTOR pathways using afatinib and AZD8055 synergistically reduced cell viability in chordoma cell lines. Importantly, this dual inhibition completely suppressed tumor growth in vivo, showing improved tumor control. Together, these data demonstrate that individual inhibitors of EGFR, c-MET, and mTOR pathways suppress chordoma growth both in vitro and in vivo. mTOR inhibition increased the efficacy of EGFR inhibition on chordoma growth in several preclinical models. The insights gained from our study potentially provide a novel combination therapeutic strategy for patients with chordoma. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons, Ltd. on behalf of The Pathological Society of Great Britain and Ireland.
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http://dx.doi.org/10.1002/path.5739DOI Listing
September 2021

Comparative characterization of two putative duplicated sodium channel genes in the red flour beetle, Tribolium castaneum.

Pestic Biochem Physiol 2021 Jun 7;175:104851. Epub 2021 Apr 7.

College of Horticulture and Plant Protection, Yangzhou University, Yangzhou 225009, China. Electronic address:

The insect voltage-gated sodium channel is the primary target of pyrethroids and novel efficient insecticides such as indoxacarb and metaflumizone. In this study, we cloned and characterized two putative sodium channel genes, TcNav1 and TcNav2, in Tribolium castaneum. The composite TcNav1 and TcNav2 encode a protein of 2045 and 2037 amino acid residues, sharing 76.1% and 75.5% amino acid identity with Drosophila para, respectively. Comparative analysis of genomic organization showed that TcNav1 and TcNav2 contain 26 and 27 exons, respectively. Analysis of the expression patterns showed that the mRNA levels of TcNav1 and TcNav2 were predominantly expressed in the head. RNAi-mediated knockdown of both TcNav1 and TcNav2 adversely affected adult emergence and significantly decreased sensitivity to deltamethrin. Significantly reduced pupation rate and sensitivity to beta-cypermethrin were observed after injection of siRNA targeting TcNav1 but not TcNav2. Taken together, we provide evidence that sodium channel gene has undergone duplication in T. castaneum, resulting in diversified developmental and toxicological functions.
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http://dx.doi.org/10.1016/j.pestbp.2021.104851DOI Listing
June 2021

Supercontinuum generation of 314.7  W ranging from 390 to 2400  nm by tapered photonic crystal fiber.

Opt Lett 2021 Mar;46(6):1429-1432

To consider both high-power handling and blue-extended supercontinuum (SC) generation, a long-tapered photonic crystal fiber is pumped by a high-power laser source. An SC ranging from 390 to 2400 nm with 314.7 W output power is obtained. A spectral component below 960 nm accounts for 36.1% of the total output power, exceeding 113.5 W, with a spectral flatness within 16 dB. To the best of our knowledge, this is the first time an SC coverage of all visible wavelengths with more than 300 W output power has been achieved. This result increases the output power of the SC covering the visible range by a factor of three.
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http://dx.doi.org/10.1364/OL.420707DOI Listing
March 2021

Curved retina-like camera array imaging system with adjustable super-resolution fovea.

Appl Opt 2021 Feb;60(6):1535-1543

To achieve non-uniform imaging with a large field of view and high efficiency as well as to obtain an adjustable fovea with super-resolution, we proposed a curved retina-like camera array imaging system (CRCS), which is built by an eight-camera array distributed non-uniformly on a curved surface and a camera coaxial with Risley prisms located in the center. By the non-uniform imaging, the field of view of the developed prototype is 150×40 with a reduction of data redundancy by 87.62%. Besides, the experimental results show that CRCS can obtain clear and sharp images of farther targets of interest around the fovea field of view with a constant focal length.
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http://dx.doi.org/10.1364/AO.417466DOI Listing
February 2021

High-Temperature Oxidation Properties and Microstructural Evolution of Nanostructure Fe-Cr-Al ODS Alloys.

Materials (Basel) 2021 Jan 22;14(3). Epub 2021 Jan 22.

School of Materials Science and Engineering, Shenyang University of Technology, Shenyang 110870, China.

The oxidation behavior and microstructural evolution of the nanostructure of Fe-Cr-Al oxide dispersion strengthened (ODS) alloys prepared by spark plasma sintering were investigated by high-temperature oxidation experiments in air at 1200 °C for 100 h. The formation of AlO scale was observed by X-ray diffraction (XRD) and scanning electron microscopy (SEM) with energy-dispersive X-ray spectroscopy (EDS) line scans. The oxidation rate of Fe-Cr-Al ODS alloys is lower than that of conventional Fe-Cr-Al alloys, and the oxide layer formed on the Fe-Cr-Al alloy appeared loose and cracked, whereas the oxide layer formed on the Fe-Cr-Al ODS alloys was adherent and flat. This is due to the high density of dispersed nano-oxides hindering the diffusion of Al element and the formation of vacancies caused by them. In addition, the nano-oxides could also adhere to the oxide layer. Besides, the microstructure of the Fe-Cr-Al ODS alloy had excellent stability during high-temperature oxidation.
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http://dx.doi.org/10.3390/ma14030526DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865709PMC
January 2021

Associations between sleep duration, lung function, FeNO and blood eosinophils among current asthmatics (NHANES 2007-12).

J Breath Res 2021 01 23;15(2):026008. Epub 2021 Jan 23.

Department of Respiratory and Critical Care Medicine, The First College of Clinical Medicine Science, China Three Gorges University, Yichang 443003, People's Republic of China. Department of Respiratory and Critical Care Medicine, Yichang Central People's Hospital, Yichang, People's Republic of China. Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Zhangzhidong Road No. 99, Wuhan 430060, People's Republic of China.

Short sleep duration potentially affects the risk of developing asthma and asthmatic exacerbation. Our aim is to determine the associations between sleep duration with asthmatic phenotypes, fraction of exhaled NO (FeNO), blood eosinophils, and lung function among current asthmatics. A total of 558 individuals from the National Health and Nutrition Examination Survey during 2007-2012 were included in this study. Self-reported sleep duration was divided into three groups: short (⩽6 h), healthy (7-8 h) and long (⩾9 h). By using a multivariate generalized additive model with binomial or Poisson regression, the abovementioned associations were evaluated after adjustment for potential confounders. Our study population included 284 short sleepers, 240 healthy sleepers and 34 long sleepers. In multivariate binomial regression analysis, we found that short sleep duration was associated with increased risk of asthma with central obesity (adjusted OR = 0.58, 95%CI: 0.33-0.99, P = 0.047) compared with healthy sleep duration. Multivariate Poisson regression analyses revealed a significant increase in FeNO (adjusted OR = 1.19, 95%CI: 1.14-1.26, P < 0.01) and reduction of blood eosinophil percentage (adjusted OR = 0.86, 95%CI: 0.77-0.96, P < 0.01) in the healthy sleep duration group compared with the short sleep duration group. The individuals with healthy and long sleep duration harbored better lung function than those with short sleep duration, with the exception of FEV1/FVC. Our study suggested that short sleepers potentially increase the risk of asthma with central obesity and lung function impairment than healthy sleepers among current asthmatics. We also observed that short sleep duration is associated with a significant reduction of FeNO and increase of blood eosinophil percentage.
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http://dx.doi.org/10.1088/1752-7163/abd192DOI Listing
January 2021

The Role of Gallstones in Gallbladder Cancer in India: A Mendelian Randomization Study.

Cancer Epidemiol Biomarkers Prev 2021 02 13;30(2):396-403. Epub 2020 Nov 13.

Centre for Cancer Epidemiology, Tata Memorial Centre, Kharghar, Navi Mumbai, Maharashtra, India.

Background: Past history of gallstones is associated with increased risk of gallbladder cancer in observational studies. We conducted complementary observational and Mendelian randomization (MR) analyses to determine whether history of gallstones is causally related to development of gallbladder cancer in an Indian population.

Methods: To investigate associations between history of gallstones and gallbladder cancer, we used questionnaire and imaging data from a gallbladder cancer case-control study conducted at Tata Memorial Hospital, Mumbai, Maharashtra, India (cases = 1,170; controls = 2,525). We then used 26 genetic variants identified in a genome-wide association study of 27,174 gallstone cases and 736,838 controls of European ancestry in an MR approach to assess causality. The association of these genetic variants with both gallstones and gallbladder cancer was examined in the gallbladder cancer case-control study. Various complementary MR approaches were used to evaluate the robustness of our results in the presence of pleiotropy and heterogeneity, and to consider the suitability of the selected SNPs as genetic instruments for gallstones in an Indian population.

Results: We found a strong observational association between gallstones and gallbladder cancer using self-reported history of gallstones [OR = 4.5; 95% confidence interval (CI) = 3.5-5.8] and with objective measures of gallstone presence using imaging techniques (OR = 2.0; 95% CI = 1.5-2.7). We found consistent causal estimates across all MR techniques, with ORs for gallbladder cancer in the range of 1.3-1.6.

Conclusions: Our findings indicate a causal relationship between history of gallstones and increased risk of gallbladder cancer, albeit of a smaller magnitude than those found in observational analysis.

Impact: Our findings emphasize the importance of gallstone treatment for preventing gallbladder cancer in high-risk individuals.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7611244PMC
February 2021

Modeling Study of Selenium Migration Behavior in Wet Flue Gas Desulfurization Spray Towers.

Environ Sci Technol 2020 12 22;54(24):16128-16137. Epub 2020 Oct 22.

State Key Laboratory of Coal Combustion (SKLCC), School of Energy and Power Engineering, Huazhong University of Science and Technology, Wuhan, Hubei 430074, China.

Wet flue gas desulfurization (WFGD) system is the core equipment for removing SO from coal-fired power plants, and it also has an important synergistic effect on the removal of selenium. However, the removal efficiency of Se across WFGD systems is not as expected, and it varies greatly in different coal-fired units (12.5-96%). In this study, a mathematical model was established to quantitatively describe the selenium migration behavior in WFGD spray towers, including the conversion of gaseous selenium to particulate selenium and the capture of gaseous SeO and particles by droplets. The calculation results show that the behavior of selenium in the spray tower can be divided into three stages: preparation, condensation, and removal. The condensation stage significantly affected the selenium distribution and its total removal efficiency. Furthermore, five factors which may affect the selenium behavior were investigated. Among them, the inlet particle size distribution and the droplet temperature had great impacts on the outlet selenium concentration, which may be the reason for the unstable selenium removal efficiencies. This study can help in understanding the migration process of selenium in WFGD spray towers and provide some guidance for the development of specific selenium control technologies.
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http://dx.doi.org/10.1021/acs.est.0c04700DOI Listing
December 2020

Effect of Hot Rolling on the Microstructure and Properties of Nanostructured 15Cr ODS Alloys with Al and Zr Addition.

Materials (Basel) 2020 Aug 21;13(17). Epub 2020 Aug 21.

School of Materials Science and Engineering, Shenyang University of Technology, Shenyang 110870, China.

Oxide dispersion strengthened (ODS) alloys with Al and Zr addition have excellent radiation tolerance, high-temperature strength, and corrosion resistance. The 15Cr-Al-Zr-ODS alloys are processed by mechanical alloying (MA), hot isostatic pressing (HIP), subsequent hot rolling to large strains of 70%, and further annealing. The effect of hot rolling on the microstructure, and the properties of nanostructured 15Cr ODS alloys with Al and Zr addition, were investigated. The microstructure after hot rolling and annealing showed obvious anisotropy. The cubic texture (φ1 = 0°, Φ = 0°, φ2 = 0°) {0 0 1} <1 0 0> and brass-R texture (φ1 = 0°, Φ = 55°, φ2 = 45°) {1 1 1} <1 1 0> were observed. The similar size distribution of precipitates was obtained for the comparison of the hot rolling samples with the hot isostatic pressed samples, which can be attributed to excellent thermal stability. After hot rolling, the alloy showed higher yield strength but did not lose too much plasticity.
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http://dx.doi.org/10.3390/ma13173695DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504106PMC
August 2020

Rapamycin improves renal injury induced by Iodixanol in diabetic rats by deactivating the mTOR/p70S6K signaling pathway.

Life Sci 2020 Oct 14;259:118284. Epub 2020 Aug 14.

Department of Radiology, The First Affiliated Hospital of China Medical University, Shenyang, China. Electronic address:

Aims: To study how to effectively prevent or reduce renal injury caused by contrast agents in diabetic patients.

Main Methods: Sprague Dawley (SD) rats were bred with a high-fat diet for eight weeks, then intraperitoneally injected with Streptozotocin (STZ) to prepare the diabetes model. Rats were treated with Iodixanol to prepare a contrast-induced acute kidney injury (CIAKI) model. Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, was administrated to diabetic rats with or without Rapamycin treatment. Serum creatinine (SCr) and blood urea nitrogen (BUN) were examined using Biochemical detector. Kidney injury molecule-1 (KIM-1), N-acetyl-β-D-amino glycosidase (NAG) in urine, inflammatory and oxidative stress factors in serum were determined by ELISA. The expression level of ROS was quantified by immunofluorescence (IF). The protein expressions of Bax, BCl-2, LC3, Beclin1, mTOR and p70S6K in renal tissue were detected by Western blot.

Key Findings: Rapamycin was demonstrated to improve renal injury induced by Iodixanol diabetic rats, decrease the levels of SCr, BUN, KIM-1, NAG, improve renal functions, reduce inflammatory response and oxidative stress injury, down-regulate Bax, while up-regulate BCl-2 and inhibit apoptosis. Moreover, Rapamycin could inhibit the phosphorylation of mTOR/p70S6K pathway-associated proteins, activate autophagy and increase the levels of LC3 and Beclin1. After treatment with 3MA, an inhibitor of mTOR/p70S6K signaling pathway, the protective effects of Rapamycin on CIAKI were weakened.

Significance: Rapamycin can alleviate renal injury induced by Iodixanol diabetic rats, and its regulatory mechanisms may be related to the regulation of mTOR/p70S6K signaling pathway and the activating autophagy.
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http://dx.doi.org/10.1016/j.lfs.2020.118284DOI Listing
October 2020

IL-1β/IL-1R1 signaling induced by intranasal lipopolysaccharide infusion regulates alpha-Synuclein pathology in the olfactory bulb, substantia nigra and striatum.

Brain Pathol 2020 11 4;30(6):1102-1118. Epub 2020 Aug 4.

Department of Geriatric Medicine, Affiliated Hospital of Xuzhou Medical University, Xuzhou, 221004, China.

Olfactory dysfunction is one of the early symptoms seen in Parkinson's disease (PD). However, the mechanisms underlying olfactory pathology that impacts PD disease progression and post-mortem appearance of alpha-Synuclein (α-Syn) inclusions in and beyond olfactory bulb in PD remain unclear. It has been suggested that environmental toxins inhaled through the nose can induce inflammation in the olfactory bulb (OB), where Lewy body (LB) is the first to be found, and then, spread to related brain regions. We hypothesize that OB inflammation triggers local α-Syn pathology and promotes its spreading to cause PD. In this study, we evaluated this hypothesis by intranasal infusion of lipopolysaccharides (LPS) to induce OB inflammation in mice and examined cytokines expression and PD-like pathology. We found intranasal LPS-induced microglia activation, inflammatory cytokine expression and α-Syn overexpression and aggregation in the OB via interleukin-1β (IL-1β)/IL-1 receptor type I (IL-1R1) dependent signaling. In addition, an aberrant form of α-Syn, the phosphorylated serine 129 α-Syn (pS129 α-Syn), was found in the OB, substantia nigra (SN) and striatum 6 weeks after the LPS treatment. Moreover, 6 weeks after the LPS treatment, mice showed reduced SN tyrosine hydroxylase, decreased striatal dopaminergic metabolites and PD-like behaviors. These changes were blunted in IL-1R1 deficient mice. Further studies found the LPS treatment inhibited IL-1R1-dependent autophagy in the OB. These results suggest that IL-1β/IL-1R1 signaling in OB play a vital role in the induction and propagation of aberrant α-Syn, which may ultimately trigger PD pathology.
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http://dx.doi.org/10.1111/bpa.12886DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754320PMC
November 2020

Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers.

Nat Commun 2020 07 3;11(1):3353. Epub 2020 Jul 3.

Section of Epidemiology and Biostatistics, Leeds Institute of Cancer and Pathology, University of Leeds, Leeds, UK.

Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.
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http://dx.doi.org/10.1038/s41467-020-16483-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335068PMC
July 2020

Mental Health Problems during the COVID-19 Pandemics and the Mitigation Effects of Exercise: A Longitudinal Study of College Students in China.

Int J Environ Res Public Health 2020 05 25;17(10). Epub 2020 May 25.

Research Centre for Public Health, Tsinghua University, Beijing 10084, China.

(1) Background: The novel coronavirus disease 2019 (COVID-19) is a global public health emergency that has caused worldwide concern. Vast resources have been allocated to control the pandemic and treat patients. However, little attention has been paid to the adverse impact on mental health or effective mitigation strategies to improve mental health. (2) Purpose: The aim of this study was to assess the adverse impact of the COVID-19 outbreak on Chinese college students' mental health, understand the underlying mechanisms, and explore feasible mitigation strategies. (3) Methods: During the peak time of the COVID-19 outbreak in China, we conducted longitudinal surveys of sixty-six college students. Structured questionnaires collected information on demographics, physical activity, negative emotions, sleep quality, and aggressiveness level. A mixed-effect model was used to evaluate associations between variables, and the mediating effect of sleep quality was further explored. A generalized additive model was used to determine the dose-response relationships between the COVID-19 death count, physical activity, and negative emotions. (4) Results: The COVID-19 death count showed a direct negative impact on general sleep quality (β = 1.37, 95% confidence interval [95% CI]: 0.55, 2.19) and reduced aggressiveness (β = -6.57, 95% CI: -12.78, -0.36). In contrast, the COVID-19 death count imposed not a direct but an indirect impact on general negative emotions (indirect effect (IE) = 0.81, = 0.012), stress (IE = 0.40, < 0.001), and anxiety (IE = 0.27, = 0.004) with sleep quality as a mediator. Moreover, physical activity directly alleviated general negative emotions (β = -0.12, 95% CI: -0.22, -0.01), and the maximal mitigation effect occurred when weekly physical activity was about 2500 METs. (5) Conclusions: (a) The severity of the COVID-19 outbreak has an indirect effect on negative emotions by affecting sleep quality. (b) A possible mitigation strategy for improving mental health includes taking suitable amounts of daily physical activity and sleeping well.
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http://dx.doi.org/10.3390/ijerph17103722DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7277113PMC
May 2020

Genome-wide association study identifies 32 novel breast cancer susceptibility loci from overall and subtype-specific analyses.

Nat Genet 2020 06 18;52(6):572-581. Epub 2020 May 18.

Molecular Medicine Unit, Fundación Pública Galega de Medicina Xenómica, Santiago de Compostela, Spain.

Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype. To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 × 10), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.
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http://dx.doi.org/10.1038/s41588-020-0609-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808397PMC
June 2020

Genome-wide assessment of population structure and genetic diversity of Chinese Lou onion using specific length amplified fragment (SLAF) sequencing.

PLoS One 2020 5;15(5):e0231753. Epub 2020 May 5.

School of Agriculture, Ningxia University, Yinchuan, China.

Lou onion (Allium fistulosum L. var. viviparum) is an abundant source of flavonols which provides additional health benefits to diseases. Genome-wide specific length amplified fragment (SLAF) sequencing method is a rapidly developed deep sequencing technologies used for selection and identification of genetic loci or markers. This study aimed to elucidate the genetic diversity of 122 onion accessions in China using the SLAF-seq method. A set of 122 onion accessions including 107 A.fistulosum L. var. viviparum Makino, 3 A.fistulosum L. var. gigantum Makino, 3 A.mongolicum Regel and 9 A.cepa L. accessions (3 whites, 3 reds and 3 yellows) from different regions in China were enrolled. Genomic DNA was isolated from young leaves and prepared for the SLAF-seq, which generated a total of 1,387.55 M reads and 162,321 high quality SNPs (integrity >0.5 and MAF >0.05). These SNPs were used for the construction of neighbor-joining phylogenetic tree, in which 10 A.fistulosum L. var. viviparum Makino accessions from Yinchuan (Ningxia province) and Datong (Qinghai province) had close genetic relationship. The 3 A.cepa L. clusters (red, white and yellow) had close genetic relationship especially with the 97 A.fistulosum L. var. viviparum Makino accessions. Population structure analysis suggested entire population could be clustered into 3 groups, while principal component analysis (PCA) showed there were 4 genetic groups. We confirmed the SLAF-seq approach was effective in genetic diversity analysis in red onion accessions. The key findings would provide a reference to the Lou onion germplasm in China.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231753PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7199963PMC
July 2020

Overlap detection on long, error-prone sequencing reads via smooth q-gram.

Bioinformatics 2020 12;36(19):4838-4845

Department of Computer Science, Indiana University Bloomington, Bloomington, IN 47405, USA.

Motivation: Third generation sequencing techniques, such as the Single Molecule Real Time technique from PacBio and the MinION technique from Oxford Nanopore, can generate long, error-prone sequencing reads which pose new challenges for fragment assembly algorithms. In this paper, we study the overlap detection problem for error-prone reads, which is the first and most critical step in the de novo fragment assembly. We observe that all the state-of-the-art methods cannot achieve an ideal accuracy for overlap detection (in terms of relatively low precision and recall) due to the high sequencing error rates, especially when the overlap lengths between reads are relatively short (e.g. <2000 bases). This limitation appears inherent to these algorithms due to their usage of q-gram-based seeds under the seed-extension framework.

Results: We propose smooth q-gram, a variant of q-gram that captures q-gram pairs within small edit distances and design a novel algorithm for detecting overlapping reads using smooth q-gram-based seeds. We implemented the algorithm and tested it on both PacBio and Nanopore sequencing datasets. Our benchmarking results demonstrated that our algorithm outperforms the existing q-gram-based overlap detection algorithms, especially for reads with relatively short overlapping lengths.

Availability And Implementation: The source code of our implementation in C++ is available at https://github.com/FIGOGO/smoothq.

Supplementary Information: Supplementary data are available at Bioinformatics online.
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http://dx.doi.org/10.1093/bioinformatics/btaa252DOI Listing
December 2020

Comparison of Fracture Load and Surface Wear of Microhybrid Composite and Ceramic Occlusal Veneers.

J Prosthodont 2020 Jun 24;29(5):387-393. Epub 2020 Mar 24.

Department of Prosthodontics, Peking University School and Hospital of Stomatology, Beijing, China.

Purpose: To compare in vitro fracture load, surface wear, and roughness after thermal cycling and cyclic mechanical fatigue loading among cemented microhybrid resin-based composite and ceramic occlusal veneers fabricated at two thicknesses (1.5 and 2.5 mm).

Materials And Methods: Sixty-four extracted premolars without root canal treatment were prepared and restored with occlusal veneers of two thicknesses (1.5 and 2.5 mm), using four different materials: microhybrid composite (MC), fiber-reinforced microhybrid composite (FMC), heat-pressed lithium disilicate ceramic (HPC), and computer-aided design/computer-aided manufactured lithium disilicate ceramic (CCC). The specimens underwent thermal cycling and cyclic mechanical fatigue loading, and were then subjected to fracture testing, with loads at failure recorded as fracture load. Wear and surface roughness were recorded before and after fatigue loading. Results were analyzed using one-way ANOVA, two-way ANOVA (α = 0.05).

Results: All specimens survived thermal cycling and cyclic mechanical fatigue loading. At 1.5-mm thickness, the mean fracture load of FMC was highest (3926.48 ± 556.54 N), while that of CCC was highest (3066.45 ± 559.94 N) at 2.5 mm. Regardless of thickness, the fracture load of CCC was higher than that of HPC (p = 0.004 and p = 0.023). The wear of MC and FMC was significantly higher than those of HPC and CCC (p ≤ 0.001), but was similar in terms of the wear rate of tooth enamel. HPC exhibited the lowest surface roughness after fatigue loading (p ≤ 0.001).

Conclusion: All tested occlusal veneers exhibited a fracture load considerably exceeding the maximum occlusal force in the posterior dentition. When the attainable space for restoration varies, different occlusal veneer materials should be considered. The surface wear and roughness also need to be considered when selecting materials.
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http://dx.doi.org/10.1111/jopr.13156DOI Listing
June 2020

A mixed-model approach for powerful testing of genetic associations with cancer risk incorporating tumor characteristics.

Biostatistics 2021 Oct;22(4):772-788

Department of Biostatistics, Johns Hopkins Bloomberg SPH, 615 N Wolfe St, Baltimore, MD 21205, USA; Department of Oncology, Johns Hopkins University School of Medicine SPH, 733 N Broadway, Baltimore, MD 21205, USA and Department of Epidemiology, Johns Hopkins Bloomberg SPH, 615 N Wolfe St, Baltimore, MD 21205, USA.

Cancers are routinely classified into subtypes according to various features, including histopathological characteristics and molecular markers. Previous genome-wide association studies have reported heterogeneous associations between loci and cancer subtypes. However, it is not evident what is the optimal modeling strategy for handling correlated tumor features, missing data, and increased degrees-of-freedom in the underlying tests of associations. We propose to test for genetic associations using a mixed-effect two-stage polytomous model score test (MTOP). In the first stage, a standard polytomous model is used to specify all possible subtypes defined by the cross-classification of the tumor characteristics. In the second stage, the subtype-specific case-control odds ratios are specified using a more parsimonious model based on the case-control odds ratio for a baseline subtype, and the case-case parameters associated with tumor markers. Further, to reduce the degrees-of-freedom, we specify case-case parameters for additional exploratory markers using a random-effect model. We use the Expectation-Maximization algorithm to account for missing data on tumor markers. Through simulations across a range of realistic scenarios and data from the Polish Breast Cancer Study (PBCS), we show MTOP outperforms alternative methods for identifying heterogeneous associations between risk loci and tumor subtypes. The proposed methods have been implemented in a user-friendly and high-speed R statistical package called TOP (https://github.com/andrewhaoyu/TOP).
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http://dx.doi.org/10.1093/biostatistics/kxz065DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8511944PMC
October 2021

Closed-Loop Control of Droplet Transfer in Electron-Beam Freeform Fabrication.

Sensors (Basel) 2020 Feb 10;20(3). Epub 2020 Feb 10.

Department of Mechanical Engineering, Tsinghua University, Beijing 100084, China.

In the process of electron-beam freeform fabrication deposition, the surface of the deposit layer becomes rough because of the instability of the feeding wire and the changing of the thermal diffusion condition. This will make the droplet transfer distance change in the deposition process, and the droplet transfer cannot always be stable in the liquid bridge transfer state. It is easy to form a large droplet or make wire and substrate stick together, which makes the deposition quality worsen or even interrupts the deposition process. The current electron-beam freeform fabrication deposition is mostly open-loop control, so it is urgent to realize the real-time and closed-loop control of the droplet transfer and to make it stable in the liquid bridge transfer state. In this paper, a real-time monitoring method based on machine vision is proposed for the droplet transfer of electron-beam freeform fabrication. The detection accuracy is up to ± 0.08 mm. Based on this method, the measured droplet transfer distance is fed back to the platform control system in real time. This closed-loop control system can stabilize the droplet transfer distance within ± 0.14 mm. In order to improve the detection stability of the whole system, a droplet transfer detection algorithm suitable for this scenario has been written, which improves the adaptability of the droplet transfer distance detection method by means of dilatation/erosion, local minimum value suppression, and image segmentation. This algorithm can resist multiple disturbances, such as spatter, large droplet occlusion and so on.
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http://dx.doi.org/10.3390/s20030923DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7039228PMC
February 2020

Microstructure and Low-Cycle Fatigue Behavior of Al-9Si-4Cu-0.4Mg-0.3Sc Alloy with Different Casting States.

Materials (Basel) 2020 Jan 31;13(3). Epub 2020 Jan 31.

State Key Laboratory of Rolling and Automation, Northeastern University, Shenyang 110819, China.

The low-cycle fatigue behavior of Al-9Si-4Cu-0.4Mg-0.3Sc alloy with different casting states was investigated by performing low-cycle fatigue tests and by means of observations and analysis with a scanning electron microscope (SEM) and a transmission electron microscope (TEM). It was found that the metal-mold cast and die-cast Al-9Si-4Cu-0.4Mg-0.3Sc alloys exhibited the cyclic stress response of strain hardening under all imposed total strain amplitudes. The cyclic deformation resistance and fatigue life of the metal-mold cast Al-9Si-4Cu-0.4Mg-0.3Sc alloy were lower than those of the die-cast Al-9Si-4Cu-0.4Mg-0.3Sc alloy. The plastic strain and elastic strain amplitudes of the metal-mold cast and die-cast Al-9Si-4Cu-0.4Mg-0.3Sc alloys were linearly related to the number of reversals to failure, which obeyed the Coffin-Manson and Basquin formulas, respectively. The results of TEM observation revealed that at all imposed total strain amplitudes, the cyclic deformation mechanisms of the metal-mold cast and die-cast Al-9Si-4Cu-0.4Mg-0.3Sc alloys were planar slip and wavy slip at the lower and higher strain amplitudes, respectively.
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http://dx.doi.org/10.3390/ma13030638DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7040932PMC
January 2020

The whole transcriptome regulation as a function of mitochondrial polymorphisms and aging in .

Aging (Albany NY) 2020 02 4;12(3):2453-2470. Epub 2020 Feb 4.

Department of Genetics, Xuzhou Medical University, Xuzhou, China.

Recently, mitochondrial-nuclear interaction in aging has been widely studied. However, the nuclear genome controlled by natural mitochondrial variations that influence aging has not been comprehensively understood so far. We hypothesized that mitochondrial polymorphisms could play critical roles in the aging process, probably by regulation of the whole-transcriptome expression. Our results showed that mitochondria polymorphisms not only decreased the mitochondrial mass but also miRNA, lncRNA, mRNA, circRNA and metabolite profiles. Furthermore, most genes that are associated with mitochondria show age-related expression features (P = 3.58E-35). We also constructed a differentially expressed circRNA-lncRNA-miRNA-mRNA regulatory network and a ceRNA network affected by the mitochondrial variations. In addition, Kyoto Encyclopedia of Genes and Genomes pathway analyses showed that the genes affected by the mitochondrial variation were enriched in metabolic activity. We finally constructed a multi-level regulatory network with aging which affected by the mitochondrial variation in . The interactions between these genes and metabolites have great values for further aging research. In sum, our findings provide new evidence for understanding the molecular mechanisms of how mitochondria influence aging.
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http://dx.doi.org/10.18632/aging.102754DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7041728PMC
February 2020

Damage Adaptive Titanium Alloy by in-Situ Elastic Gradual Mechanism.

Materials (Basel) 2020 Jan 15;13(2). Epub 2020 Jan 15.

School of Materials Science and Engineering, Shenyang University of Technology, Shenyang 110870, China.

Natural materials are generally damage adaptive through their multilevel architectures, with the characteristics of compositional and mechanical gradients. This study demonstrated that the desired elastic gradient can be in-situ stress-induced in a titanium alloy, and that the alloy showed extreme fatigue-damage tolerance through the crack deflection and branch due to the formation of a three-dimensional elastically graded zone surrounding the crack tip. This looks like a perceptive and adaptive mechanism to retard the crack: the higher stress concentrated at the tip and the larger elastic gradient to be induced. The retardation is so strong that a gradient nano-grained layer with a thickness of less than 2 μm formed at the crack tip due to the highly localized and accumulated plasticity. Furthermore, the ultrafine-grained alloy with the nano-sized precipitation also exhibited good damage tolerance.
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http://dx.doi.org/10.3390/ma13020406DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013576PMC
January 2020

Diesel exhaust and bladder cancer risk by pathologic stage and grade subtypes.

Environ Int 2020 02 18;135:105346. Epub 2019 Dec 18.

Occupational and Environmental Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, USA. Electronic address:

Background: The International Agency for Research on Cancer (IARC) classifies diesel engine exhaust as carcinogenic to humans based on sufficient evidence for lung cancer. IARC noted, however, an increased risk of bladder cancer (based on limited evidence).

Objective: To evaluate the association between quantitative, lifetime occupational diesel exhaust exposure and risk of urothelial cell carcinoma of the bladder (UBC) overall and according to pathological subtypes.

Methods: Data from personal interviews with 1944 UBC cases, as well as formalin-fixed paraffin-embedded tumor tissue blocks, and 2135 controls were pooled from two case-control studies conducted in the U.S. and Spain. Lifetime occupational histories combined with exposure-oriented questions were used to estimate cumulative exposure to respirable elemental carbon (REC), a primary surrogate for diesel exhaust. Unconditional logistic regression and two-stage polytomous logistic regression were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for smoking and other risk factors.

Results: Exposure to cumulative REC was associated with an increased risk of UBC; workers with cumulative REC >396 μg/m-years had an OR of 1.61 (95% CI, 1.08-2.40). At this level of cumulative exposure, similar results were observed in the U.S. and Spain, OR = 1.75 (95% CI, 0.97-3.15) and OR = 1.54 (95% CI, 0.89-2.68), respectively. In lagged analysis, we also observed a consistent increased risk among workers with cumulative REC >396 μg/m-years (range of ORs = 1.52-1.93) for all lag intervals evaluated (5-40 years). When we accounted for tumor subtypes defined by stage and grade, a significant association between diesel exhaust exposure and UBC was apparent (global test for association p = 0.0019).

Conclusions: Combining data from two large epidemiologic studies, our results provide further evidence that diesel exhaust exposure increases the risk of UBC.
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http://dx.doi.org/10.1016/j.envint.2019.105346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8237313PMC
February 2020

Rheological Law and Mechanism for Superplastic Deformation of Ti-6Al-4V.

Materials (Basel) 2019 Oct 26;12(21). Epub 2019 Oct 26.

School of Materials Science and Engineering, Shenyang University of Technology, Shenyang 110870, China.

The behaviors of and mechanisms acting in Ti-6Al-4V alloy during low-temperature superplastic deformation were systematically studied by using a Gleeble-3800 thermocompression simulation machine. Focusing on the mechanical behaviors and microstructure evolution laws during low-temperature superplastic compression tests, we clarified the changing laws of the strain rate sensitivity index, activation energy of deformation, and grain index at varying strain rates and temperatures. Hot working images based on the dynamic material model and the deformation mechanism maps involving dislocation quantity were plotted on the basis of PRASAD instability criteria. The low-temperature superplastic compression-forming technique zone and the rheological instability zone of Ti-6Al-4V were analyzed by using hot processing theories. The dislocation evolution laws and deformation mechanisms of the grain size with Burgers vector compensation and the rheological stress with modulus compensation during the low-temperature superplastic compression of Ti-6Al-4V were predicted by using deformation mechanism maps.
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http://dx.doi.org/10.3390/ma12213520DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6862498PMC
October 2019

Self-Healable Conductive Nanocellulose Nanocomposites for Biocompatible Electronic Skin Sensor Systems.

ACS Appl Mater Interfaces 2019 Nov 13;11(47):44642-44651. Epub 2019 Nov 13.

Department of Chemical Engineering, Waterloo Institute for Nanotechnology , University of Waterloo , 200 University Avenue West , Waterloo N2L 3G1 , Ontario , Canada.

Electronic skins are developed for applications such as biomedical sensors, robotic prosthetics, and human-machine interactions, which raise the interest in composite materials that possess both flexibility and sensing properties. Polypyrrole-coated cellulose nanocrystals and cellulose nanofibers were prepared using iron(III) chloride (FeCl) oxidant, which were used to reinforce polyvinyl alcohol (PVA). The combination of weak H-bonds and iron coordination bonds and the synergistic effect of these components yielded self-healing nanocomposite films with robust mechanical strength (409% increase compared to pure PVA and high toughness up to 407.1%) and excellent adhesion (9670 times greater than its own weight) to various substrates in air and water. When damaged, the nanocomposite films displayed good mechanical (72.0-76.3%) and conductive (54.9-91.2%) recovery after a healing time of 30 min. More importantly, the flexible nanocomposites possessed high strain sensitivity under subtle strains (<48.5%) with a gauge factor (GF) of 2.52, which was relatively larger than the GF of ionic hydrogel-based skin sensors. These nanocomposite films possessed superior sensing performance for real-time monitoring of large and subtle human motions (finger bending motions, swallowing, and wrist pulse); thus, they have great potentials in health monitoring, smart flexible skin sensors. and wearable electronic devices.
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http://dx.doi.org/10.1021/acsami.9b17030DOI Listing
November 2019
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