Publications by authors named "Bo Han"

756 Publications

Study on Meso-Material Parameters of Submarine Weathered Granite Based on Parallel Bond Model.

Materials (Basel) 2022 May 29;15(11). Epub 2022 May 29.

School of Civil Engineering, Shandong University, Jinan 250061, China.

In order to study the mechanical properties of submarine weathered granite under marine geological conditions, uniaxial compression tests were carried out on the original medium weathered granite of the seafloor of an offshore area in Pingtan, Fujian Province by using triaxial experimental apparatus to analyze the fracture characteristics, stress-strain characteristics, and compressive strength indexes. Based on the theory of discontinuous medium, the uniaxial compression and uniaxial tensile tests of rocks were simulated, and the microscopic mechanical parameters of discrete elements of granite samples were determined based on the indoor macroscopic mechanical tests: effective modulus E, compressive elastic modulus E, macro Poisson's ratio μ, and uniaxial compressive strength . The results show that the parallel bond model has good simulation results for the uniaxial compression test, but the tensile strength and tensile-compression ratio were quite different from the experimental values. When the confining pressure is large, the calibrated parameter adaptability by uniaxial compression is poor. The reason for certain errors is a large resistance of the parallel bond model to particle rotation and the influence of normal stress on shear strength is not considered. The cementation model can be modified by adding coefficients based on laboratory test results.
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http://dx.doi.org/10.3390/ma15113878DOI Listing
May 2022

Long-Term Exposure to Decabromodiphenyl Ether Promotes the Proliferation and Tumourigenesis of Papillary Thyroid Carcinoma by Inhibiting TRß.

Cancers (Basel) 2022 Jun 2;14(11). Epub 2022 Jun 2.

Department of Pathology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600# Yishan Rd, Shanghai 200233, China.

Polybrominated diphenyl ethers (PBDEs) have been reported to possess endocrine-disrupting and tumour-promoting activity. However, the effects of long-term exposure to decabromodiphenyl ether (BDE209) on thyroid tumourigenesis of papillary thyroid carcinoma (PTC) and the underlying mechanisms remain poorly defined. In this study, functional assays in vitro and mouse models in vivo were used to evaluate the toxic effects of long-term exposure to environmental concentrations of BDE209 on the pathogenesis and progression of PTC. MTS, EdU and colony-forming assays confirmed the chronic toxicity of BDE209 on the proliferation of human normal follicular epithelial cell line (Nthy-ori 3-1) and PTC-derived cell lines (TPC-1 and BCPAP). Wound and Transwell assays showed that BDE209 exacerbated the aggressiveness of PTC cells. BDE209 significantly promoted cell proliferation during the S and G2/M phases of the cell cycle. Mechanistically, BDE209 altered the thyroid system by acting as a competitive inhibitor of thyroid receptor beta (TRß) expression and function, which was further proven by public databases and RNA-seq bioinformation analysis. Taken together, these results demonstrated that BDE209 has chronic toxicity and potential tumourigenic effects on the thyroid by inhibiting TRß.
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http://dx.doi.org/10.3390/cancers14112772DOI Listing
June 2022

Extended : Learning with Mixed Closed-set and Open-set Noisy Labels.

IEEE Trans Pattern Anal Mach Intell 2022 Jun 8;PP. Epub 2022 Jun 8.

The noise transition matrix , reflecting the probabilities that true labels flip into noisy ones, is of vital importance to model label noise and build statistically consistent classifiers. The traditional transition matrix is limited to model closed-set label noise, where noisy training data have true class labels within the noisy label set. It is unfitted to employ such a transition matrix to model open-set label noise, where some true class labels are outside the noisy label set. Therefore, when considering a more realistic situation, i.e., both closed-set and open-set label noises occur, prior works will give unbelievable solutions. Besides, the traditional transition matrix is mostly limited to model instance-independent label noise, which may not perform well in practice. In this paper, we focus on learning with the mixed closed-set and open-set noisy labels. We address the aforementioned issues by extending the traditional transition matrix to be able to model mixed label noise, and further to the cluster-dependent transition matrix to better combat the instance-dependent label noise in real-world applications. We term the proposed transition matrix as the cluster-dependent extended transition matrix. An unbiased estimator (i.e., extended -estimator) has been designed to estimate the cluster-dependent extended transition matrix by only exploiting the noisy data. Comprehensive experiments validate that our method can better cope with realistic label noise, following its more robust performance than the prior state-of-the-art label-noise learning methods.
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http://dx.doi.org/10.1109/TPAMI.2022.3180545DOI Listing
June 2022

Neoadjuvant Hormonal Therapy for Prostate Cancer: Morphologic Features and Predictive Parameters of Therapy Response.

Adv Anat Pathol 2022 Jul 13;29(4):252-258. Epub 2022 Apr 13.

The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, Shandong University QiLu Medical College, School of Basic Medical Sciences.

The primary goals of neoadjuvant hormonal therapy (NHT) in prostate cancer (PCa) are to reduce the size of the tumor, lower positive surgical margin rate, attempt to reach pathologic remission, and improve survival. Although NHT has not been recommended by the National Comprehensive Cancer Network as a primary treatment option for patients with localized PCa, NHT is increasingly used in clinical trials for locally advanced PCa. More importantly, with the development of novel androgen signaling inhibitors, such as abiraterone and enzalutamide, there has been renewed interests in revisiting the role of such treatment in the neoadjuvant setting. Following NHT, the PCa tissues shows characteristic morphologic alterations. Of note, the collapse of malignant glands most likely leads to an artificial increase of Gleason score in the residual disease. Communicating these changes to the clinician in a way that can help assess the tumor's response poses a challenge for pathologists. In addition, little is known of morphologic features and predictive makers both in pretreated and posttreated specimens that can be of value in predicting tumor response to NHT. In the current review, we summarize the morphologic changes associated with neoadjuvant-treated PCa, focusing on the predictive value of pathologic parameters to therapy response. We also describe the evaluation system in the stratification of pathologic response to NHT in PCa management.
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http://dx.doi.org/10.1097/PAP.0000000000000347DOI Listing
July 2022

Brightening of a dark monolayer semiconductor via strong light-matter coupling in a cavity.

Nat Commun 2022 May 30;13(1):3001. Epub 2022 May 30.

Institute of Physics, Carl von Ossietzky University, Oldenburg, 26129, Germany.

Engineering the properties of quantum materials via strong light-matter coupling is a compelling research direction with a multiplicity of modern applications. Those range from modifying charge transport in organic molecules, steering particle correlation and interactions, and even controlling chemical reactions. Here, we study the modification of the material properties via strong coupling and demonstrate an effective inversion of the excitonic band-ordering in a monolayer of WSe with spin-forbidden, optically dark ground state. In our experiments, we harness the strong light-matter coupling between cavity photon and the high energy, spin-allowed bright exciton, and thus creating two bright polaritonic modes in the optical bandgap with the lower polariton mode pushed below the WSe dark state. We demonstrate that in this regime the commonly observed luminescence quenching stemming from the fast relaxation to the dark ground state is prevented, which results in the brightening of this intrinsically dark material. We probe this effective brightening by temperature-dependent photoluminescence, and we find an excellent agreement with a theoretical model accounting for the inversion of the band ordering and phonon-assisted polariton relaxation.
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http://dx.doi.org/10.1038/s41467-022-30645-5DOI Listing
May 2022

Class-Wise Denoising for Robust Learning under Label Noise.

IEEE Trans Pattern Anal Mach Intell 2022 May 30;PP. Epub 2022 May 30.

Label noise is ubiquitous in many real-world scenarios which often misleads training algorithm and brings about the degraded classification performance. Therefore, many approaches have been proposed to correct the loss function given corrupted labels to combat such label noise. Among them, a trend of works unbiasedly estimate the data centroid, which plays an important role in constructing an unbiased risk estimator. However, they usually handle the noisy labels in different classes all at once, so the local information inherited by each class is ignored. To address this defect, this paper presents a novel robust learning algorithm dubbed "Class-Wise Denoising" (CWD), which tackles the noisy labels in a class-wise way to ease the entire noise correction task. Specifically, two virtual auxiliary sets are respectively constructed by presuming that the positive and negative labels in the training set are clean, so the original false-negative labels and false-positive ones are tackled separately. As a result, an improved centroid estimator can be designed which helps to yield more accurate risk estimator. Our CWD can produce the improved classification performance under label noise, which is also demonstrated by the comparisons with ten representative state-of-the-art methods on a variety of benchmark datasets.
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http://dx.doi.org/10.1109/TPAMI.2022.3178690DOI Listing
May 2022

May the midline lumbar interbody fusion (MIDLIF) prevent the early radiographic adjacent segment degeneration? A minimum 3-year follow-up comparative study of MIDLIF in L4/5 with cortical bone trajectory screw versus traditional pedicle screw fixation.

BMC Musculoskelet Disord 2022 May 20;23(1):480. Epub 2022 May 20.

Department of Orthopedics, Beijing Chao-Yang Hospital, Capital Medical University, GongTiNanLu 8#, Chao-Yang District, Beijing, 100020, China.

Study Design: Retrospective cohort study.

Objective: To compare the early radiographic adjacent segment degeneration (R-ASD) and regional lumbar sagittal alignment after midline lumbar interbody fusion (MIDLIF) with cortical bone trajectory (CBT) screw fixation (CBT-MIDLIF) and posterior lumbar interbody fusion (PLIF) with the traditional pedicle screw fixation (PS-PLIF) during long-term follow-up.

Methods: All patients who underwent CBT-MIDLIF or PS-PLIF were identified by a retrospective consecutive case review. Radiographic parameters in cephalad adjacent segment (L3/4), including intervertebral space height (ISH), foraminal height (FH), foraminal width (FW), range of motion were assessed. Lumbar lordosis (LL), sacral slope (SS), L4-L5 Cobb angle, Cobb angle of the intervertebral space at L4-L5, and height of the anterior and posterior edges of the intervertebral space at L4-L5, were measured and compared on preoperative, postoperative, and 3-year follow-up radiographic evaluation.

Results: Seventy-four patients underwent CBT-MIDLIF (CBT-MIDLIF group) and 114 patients underwent conventional PS-PLIF (PS-PLIF group). ISH, FH and FW were significantly smaller at 6-month follow-up than before operation with PS-PLIF (p < 0.001) but showed no significant changes with CBT-MIDLIF (p > 0.05). At the last follow-up, the changes in cephalad R-ASD parameters were more remarkable after PS-PLIF than after CBT-MIDLIF (p < 0.01). LL and SS were significant larger at the last follow-up than before operation in both groups (p < 0.001). Regarding long-term outcomes, the symptoms caused by degenerative spinal disorders significantly improved in both groups (p < 0.01).

Conclusion: CBT-MIDLIF had less radiographic degeneration in the adjacent segment than PS-PLIF at 3-year follow-up. The lumbar sagittal alignment could be improved significantly and the surgical outcomes were satisfactory after either CBT-MIDLIF or PS-PLIF.
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http://dx.doi.org/10.1186/s12891-022-05363-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9121621PMC
May 2022

Genotypic characterization of multidrug resistant Escherichia coli isolates reveals co-existence of ESBL- and carbapenemase- encoding genes linked to ISCR1.

Vet Ital 2021 Dec 31;57(4):275-285. Epub 2021 Dec 31.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, P.R. China.

Antimicrobial resistance in food-producing animals has not yet judiciously been reported from Pakistan. Here, we report on the isolation rate of poultry-associated multidrug resistant extended spectrum β-lactamase (ESBL) -producing Escherichia coli in Peshawar, Pakistan. A total of 200 samples, 50 from retail-poultry meat, 50 from sick birds, 50 from the boiler farm-environment, and 50 from human beings working on or exposed to poultry were analyzed for isolation of ESBL -producing E. coli, ESBL -encoding genes and antimicrobial susceptibility. A total of 81 E. coli isolates [(50.0% Phylogroup-A, 33.3% D and 16.7% phylogroup B2)], were recovered, 36 (44.4%) of them were found to be ESBL -producers. PCR revealed that blaCTXM was the most prevalent (14/36 = 38.9%) ESBL -encoding gene followed by blaSHV2 (9/36 = 25%). Strikingly, co-occurrence of multiple ESBL - and/or carbapenemase-encoding genes in a single isolate was observed, and combination of blaCTXM + blaSHV2 was the most predominant (19.4%) followed by blaCTXM + blaNDM1 + blaOXA-48 (11.1%) and blaCTXM + blaOXA-48 (8.8%). All these ESBL producers were found to be multidrug resistant (MDR) and were carrying either integron 1 (48.5%) or 2 (51.5%). Finally, 14 of the 36 isolates were also found positive for variable region and insertion sequence common region 1, which was found linked to ESBL/carbapenemase encoding genes in 5/14 isolates suggesting its role in dissemination.
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http://dx.doi.org/10.12834/VetIt.1780.9397.4DOI Listing
December 2021

Advancements on Small Molecule PROTACs Containing an Indole/Spiro-fused Oxoindole Scaffolds: An Emerging Degrader Targeting Cancers.

Anticancer Agents Med Chem 2022 May 9. Epub 2022 May 9.

State Key Laboratory of Southwestern Chinese Medicine Resources, Hospital of Chengdu University of Traditional Chinese Medicine, School of Pharmacy and College of Medical Technology, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

Indole and spiro-fused oxoindole frameworks widely exist in a variety of natural bioactive products, pharmaceuticals and drug candidates, featuring unique functions in the regulation of proliferation, infiltration, and metastasis of cancer cells. In recent years, significant progress of proteolysis targeting chimeric (PROTAC) technology that employs ubiquitin-proteasome system (UPS) to eliminate disease-associated proteins has been witnessed, thus opening a promising avenue to the discovery of new indole-related drugs. In this review, we focus on summarizing the achievements on small molecule PROTACs that involve indole/spiro-fused oxoindole scaffolds in the part of ligands of the protein of interest (POI). Current challenges and future directions in this promising field are discussed at the end of this review. For the convenience of readers, our review is divided into five parts according to the types of target proteins. We hope this review could bring a quick look and some inspiration to researchers in relevant fields.
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http://dx.doi.org/10.2174/1871520622666220509175305DOI Listing
May 2022

Clinical Profile and Risk Factors for Cardiac Death in Pediatric Patients With Primary Dilated Cardiomyopathy at a Tertiary Medical Center in China.

Front Pediatr 2022 28;10:833434. Epub 2022 Apr 28.

Department of Pediatrics, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Aim: We sought to identify the clinical characteristics and risk factors for cardiac mortality in pediatric patients with primary dilated cardiomyopathy (DCM) in China.

Methods: A total of 138 pediatric patients who were consecutively diagnosed with primary DCM from January 2011 to December 2020 were included. We assessed patients' clinical symptoms and performed laboratory examinations, electrocardiography, and echocardiography.

Results: Of these patients, 79 (57%) had severe systolic dysfunction (left ventricular ejection fraction of < 30%), 79 (57.2%) developed DCM before 12 months of age, 62 (45%) were male, 121 (87.7%) presented with advanced heart failure (cardiac functional class III/IV), and 54 (39.1%) presented with arrhythmia. At a median follow-up of 12 months, the overall cardiac mortality rate was 33%, and 40 of 46 deaths occurred within 6 months following DCM diagnosis. A multivariate Cox regression analysis identified several independent cardiac death predictors, including an age of 12 months to 5 years [hazard ratio (HR) 2.799; 95% confidence interval (CI) 1.160-6.758; = 0.022] or 10-15 years (HR 3.617; 95% CI 1.336-9.788; = 0.011) at diagnosis, an elevated serum alanine aminotransferase (ALT) concentration (≥ 51.5 U/L) (HR 2.219; 95% CI 1.06-4.574; = 0.031), and use of mechanical ventilation (HR 4.223; 95% CI 1.763-10.114; = 0.001).

Conclusion: The mortality rate of primary DCM without transplantation is high. Age, an elevated serum ALT concentration, and the need for mechanical ventilation predict mortality in patients with primary DCM, providing new insights into DCM risk stratification.
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http://dx.doi.org/10.3389/fped.2022.833434DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9096786PMC
April 2022

Label-free Quantitative Proteomic Analysis of Cerebrospinal Fluid and Serum in Patients With Relapse-Remitting Multiple Sclerosis.

Front Genet 2022 27;13:892491. Epub 2022 Apr 27.

Department of Neurology, Baoding No. 1 Central Hospital, Baoding, China.

The lack of effective serum and cerebrospinal fluid (CSF) biomarkers remains a barrier to early diagnosis and treatment of multiple sclerosis (MS). The study is to identify the diagnostic biomarkers of serum and CSF in patients who suffered MS. At first, we performed differential analysis of CSF and serum proteomics on control and relapse-remitting multiple sclerosis (RRMS) patients. Secondly, CSF and serum's differential proteins were compared, in order to identify the significative proteins. Finally, Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis were performed on the differential proteins in serum and CSF respectively to clarify their common biological functions and pathways. At the first step, in CSF, 73 proteins were significantly differentially expressed in the RRMS set compared with the controls. In serum, 22 proteins were differentially expressed. Secondly, we found MMP2 C8G and CFH were the same high expression trend in CSF and serum. Finally, we found the differential proteins in serum and CSF are mostly participated in biological processes: immuno-inflammatory response, neuronal development, cell adhesion and signaling. MMP2, C8G and CFH may participate in the pathogenesis of RRMS, which are the potential diagnostic biomarkers of the disease.
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http://dx.doi.org/10.3389/fgene.2022.892491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9092947PMC
April 2022

Comparison of Deep Inspiration Breath Hold Versus Free Breathing in Radiotherapy for Left Sided Breast Cancer.

Front Oncol 2022 21;12:845037. Epub 2022 Apr 21.

Department of Radiation Oncology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.

Objectives: Modern breast cancer techniques, such as the deep inspiration breath-hold (DIBH) technique has been applied for left-sided breast cancer. Whether the DIBH regimen is the optimal solution for left-sided breast cancer remains unclear. This meta-analysis aims to elucidate the differences of DIBH and free-breathing (FB) for patients receiving radiotherapy for left-sided breast cancer and provide a practical reference for clinical practice.

Methods: Relevant research available on PubMed, Embase, Cochrane Library, and the Web of Science published before November 30, 2021 was independently and systematically examined by two investigators. Data were extracted from eligible studies for assessing their qualities and calculating the standardized mean difference (SMD) and 95% confidence intervals (CIs) using Review Manager software 5.4 (RevMan 5.4).

Results: Forty-one studies with a total of 3599 left-sided breast cancer patients were included in the meta-analysis. Compared with FB, DIBH reduced heart dose ( , , V30, V10, V5), left anterior descending branch (LAD) dose ( , ), ipsilateral lung dose ( , V20, V10, V5), and heart volume significantly. Lung volume increased greatly, and a statistically significant difference. For contralateral breast mean dose, DIBH has no obvious advantage over FB. The funnel plot suggested this study has no significant publication bias.

Conclusions: Although DIBH has no obvious advantage over FB in contralateral breast mean dose, it can significantly reduce heart dose, LAD dose, ipsilateral lung dose, and heart volume. Conversely, it can remarkably increase the ipsilateral lung volume. This study suggests that soon DIBH could be more widely utilized in clinical practice because of its excellent dosimetric performance.
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http://dx.doi.org/10.3389/fonc.2022.845037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9069140PMC
April 2022

RUVBL1 promotes enzalutamide resistance of prostate tumors through the PLXNA1-CRAF-MAPK pathway.

Oncogene 2022 06 4;41(23):3239-3250. Epub 2022 May 4.

The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Shandong University, Jinan, Shandong, 250012, China.

Although enzalutamide improves the overall survival of patients with metastatic prostate cancers, enzalutamide resistance (ENZR) will be inevitably developed. Emerging evidence support that alternative oncogenic pathways may bypass the androgen receptor (AR) signaling to promote ENZR progression, however, the underpinning mechanisms remain poorly defined. Here, we report that the expression of RuvB like AAA ATPase 1 (RUVBL1) is upregulated in ENZR cells and xenograft models and prostate tumors in patients. Enzalutamide increases RUVBL1 accumulation in the cytoplasm, which in turn enhances the recruitment of CRAF proto-oncogene serine/threonine kinase protein to plexin A1 (PLXNA1) and the subsequent activation of the downstream MAPK pathway. Co-overexpression of RUVBL1 and PLXNA1 defines a subgroup of prostate cancer (PCa) patients with a poor prognosis. Furthermore, pharmacological inhibition of RUVBL1 by CB-6644 suppresses ENZR cell proliferation and xenograft growth and allows re-sensitization of ENZR cells and xenografts to enzalutamide, indicating that RUVBL1 may act to substitute the AR signaling to promote cancer cell survival and ENZR development. Together, these findings may lead to the identification of RUVBL1 as a potential therapeutic target for ENZR tumors.
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http://dx.doi.org/10.1038/s41388-022-02332-8DOI Listing
June 2022

Ligand-enabled and magnesium-activated hydrogenation with earth-abundant cobalt catalysts.

RSC Adv 2021 Dec 15;11(63):39934-39939. Epub 2021 Dec 15.

Laboratory of New Energy & New Function Materials, Shaanxi Key Laboratory of Chemical Reaction Engineering, College of Chemistry and Chemical Engineering, Yan'an University Yan'an 716000 P. R. China

Replacing expensive noble metals like Pt, Pd, Ir, Ru, and Rh with inexpensive earth-abundant metals like cobalt (Co) is attracting wider research interest in catalysis. Cobalt catalysts are now undergoing a renaissance in hydrogenation reactions. Herein, we describe a hydrogenation method for polycyclic aromatic hydrocarbons (PAHs) and olefins with a magnesium-activated earth-abundant Co catalyst. When diketimine was used as a ligand, simple and inexpensive metal salts of CoBr in combination with magnesium showed high catalytic activity in the site-selective hydrogenation of challenging PAHs under mild conditions. Co-catalyzed hydrogenation enabled the reduction of two side aromatics of PAHs. A wide range of PAHs can be hydrogenated in a site-selective manner, which provides a cost-effective, clean, and selective strategy to prepare partially reduced polycyclic hydrocarbon motifs that are otherwise difficult to prepare by common methods. The use of well-defined diketimine-ligated Co complexes as precatalysts for selective hydrogenation of PAHs and olefins is also demonstrated.
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http://dx.doi.org/10.1039/d1ra07266hDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044643PMC
December 2021

Deep Learning From Multiple Noisy Annotators as A Union.

IEEE Trans Neural Netw Learn Syst 2022 Apr 29;PP. Epub 2022 Apr 29.

Crowdsourcing is a popular solution for large-scale data annotations. So far, various end-to-end deep learning methods have been proposed to improve the practical performance of learning from crowds. Despite their practical effectiveness, most of them have two major limitations--they do not hold learning consistency and suffer from computational inefficiency. In this article, we propose a novel method named UnionNet, which is not only theoretically consistent but also experimentally effective and efficient. Specifically, unlike existing methods that either fit a given label from each annotator independently or fuse all the labels into a reliable one, we concatenate the one-hot encoded vectors of crowdsourced labels provided by all the annotators, which takes all the labeling information as a union and coordinates multiple annotators. In this way, we can directly train an end-to-end deep neural network by maximizing the likelihood of this union with only a parametric transition matrix. We theoretically prove the learning consistency and experimentally show the effectiveness and efficiency of our proposed method.
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http://dx.doi.org/10.1109/TNNLS.2022.3168696DOI Listing
April 2022

Successful phytotherapy for a patient with severe immune thrombocytopenia and failed with corticosteroids, azathioprine, eltrombopag, and platelet transfusion - A case report.

Explore (NY) 2022 Apr 11. Epub 2022 Apr 11.

Tissue Engineering and Drug Discovery Laboratory, Department of Surgery, University of Southern California.

The purpose of this study was to investigate and evaluate the effectiveness of phytotherapy on a severe and complicated Immune Thrombocytopenia (ITP) patient who had failed with conventional treatments. A male patient presented with clinical symptoms of ITP and had been treated with Corticosteroids, Azathioprine, Eltrombopag, and platelet transfusions for over three years. The patient had an initial response but later developed severe complications, including hydrothorax, gastric pain, hematuria, and digestive hemorrhage, and no further response to treatment. The patient then received Phytotherapy for 17 months which significantly improved the clinical symptoms, platelet counts, and laboratory tests. Despite his active lifestyle, the patient was symptom-free with platelet counts ranging from 109 to 132×10/L.
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http://dx.doi.org/10.1016/j.explore.2022.04.005DOI Listing
April 2022

molecular dynamics study on the disordered Li-Ga-Sn system.

Phys Chem Chem Phys 2022 May 4;24(17):10537-10547. Epub 2022 May 4.

Institute for Applied Materials (IAM-AWP), Karlsruhe Institute of Technology, 76344, Eggenstein-Leopoldshafen, Germany.

The eutectic GaSn liquid metal could serve as the anode in Li-ion batteries to avoid dendrite growth issue and volume expansion, and maintain a good cycle life. However, the microstructure and the basic physical properties of the lithiated GaSn are ignored in experiments and still unclear. In this work, we assume that a disordered structure is formed in the initial stage of lithiation of GaSn, and the structure, equilibrium density, thermal expansion coefficient, mixing enthalpy, self-diffusion coefficient and viscosity of the disordered Li-Ga-Sn system are investigated systematically by molecular dynamics. The radial distribution function, structure factor and bond angle distribution function are calculated to obtain local structure information. Our calculations show that the lithiation of GaSn is exothermic, and for most cases, the diffusion coefficients for Li, Ga and Sn decrease with increasing Li content. Based on structural information and diffusion coefficients, we reveal that the lithiation of GaSn will make the liquid GaSn alloy form a solid-like structure. With the increase of Li content, it is more likely to form a solid-like structure. Furthermore, our simulations reveal that the chemical interaction of Li-Sn and Li-Ga is stronger than that of Ga-Sn, and Li is prone to combine with Sn firstly in the lithiation process of GaSn.
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http://dx.doi.org/10.1039/d2cp00618aDOI Listing
May 2022

What Are the Benefits of Lateral Lumbar Interbody Fusion on the Treatment of Adult Spinal Deformity: A Systematic Review and Meta-Analysis Deformity.

Global Spine J 2022 Apr 20:21925682221089876. Epub 2022 Apr 20.

Department of Orthopedic Surgery, 74639Beijing Chao-Yang Hospital, Beijing, China.

Study Design: A systematic review and meta-analysis.

Objective: The purpose of this systematic review and meta-analysis was to compare the efficacy of lateral lumbar interbody fusion (LLIF) combined with posterior spinal fusion (PSF) with that of conventional PSF in the treatment of adult spinal deformity (ASD).

Methods: A comprehensive literature search was performed for relevant studies in PubMed, EMBASE, Web of Science, and the Cochrane Library. Spinopelvic parameters, surgical data, complications, and clinical outcomes at the last follow-up were compared between patients with ASD who underwent LLIF combined with PSF (LLIF+PSF group) and those who underwent conventional PSF (only-PSF group).

Results: Ten studies, comprising 621 patients with ASD (313 in the LLIF+PSF group and 308 in the only-PSF group), were included. The level of evidence was III for 7 studies and IV for 3 studies. There was no significant difference in the improvement in the visual analog scale score, systemic complication rate, and revision rate between groups. In the LLIF+PSF group, we noted a superior restoration of lumbar lordosis (weighted mean difference [WMD], 9.77; 95% confidence interval [CI] 7.10 to 12.44, < .001), pelvic tilt (WMD, -2.50; 95% CI -4.25 to -.75, = .005), sagittal vertical axis (WMD, -21.92; 95% CI -30.73 to -13.11, < .001), and C7 plumb line-center sacral vertical line (WMD, -4.03; 95% CI -7.52 to -.54, = .024); a lower estimated blood loss (WMD, -719.99; 95% CI -1105.02 to -334.96, < .001) while a prolonged operating time (WMD, 104.89; 95% CI 49.36 to 160.43, < .001); lower incidence of pseudarthrosis (risk ratio [RR], .26; 95% CI .08 to .79, = .017) while higher incidence of neurologic deficits (RR, 2.04; 95% CI 1.27 to 3.25, = .003); and a better improvement in Oswestry Disability Index score (WMD, -7.04; 95% CI -10.155 to -3.93, < .001) and Scoliosis Research Society-22 total score (WMD, .27; 95% CI .11 to .42, = .001). The level of evidence in this systematic review and meta-analysis was II.

Conclusion: Compared with conventional PSF, LLIF combined with PSF was associated with superior restoration of sagittal and coronal alignment, lower incidence of pseudarthrosis, better improvement in quality of life, and less surgical invasiveness in the treatment of ASD, albeit at the cost of prolonged surgical times and substantially high incidence of lower extremity symptoms. Surgeons should weigh the advantages and disadvantages of this procedure, and inform patients about its side effects.
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http://dx.doi.org/10.1177/21925682221089876DOI Listing
April 2022

Nrf2 and NF-κB/NLRP3 inflammasome pathways are involved in Prototheca bovis infections of mouse mammary gland tissue and mammary epithelial cells.

Free Radic Biol Med 2022 May 10;184:148-157. Epub 2022 Apr 10.

Department of Clinical Veterinary Medicine, College of Veterinary Medicine, China Agricultural University, Beijing, 100193, PR China. Electronic address:

Prototheca bovis is a serious pathogen for animals, but pathogenesis of P. bovis mastitis is unclear. The objective was to characterize how P. bovis induces inflammatory responses in mouse mammary gland tissue and mammary epithelial cells (mMECs). Prototheca bovis damaged mammary gland tissue and mitochondrial structure, and induced oxidative stress, as evident by significant increases in mtROS and MDA concentrations and significant decreases in T-SOD activity in both mammary gland tissue and mMECs. Expression of Nrf2, HO-1 and Keap1 proteins was significantly changed in mammary gland tissue and mMECs after P. bovis infection. Additionally, cytokines (IL-1β, IL-6 and IL-18) and protein expressions in NF-κB and in the NLRP3 inflammasome pathway were significantly increased in mammary gland tissue and mMECs. In the P. bovis group, treatment with N-acetyl-l-cysteine (NAC) significantly decreased protein expression in NF-κB and the NLRP3 inflammasome pathway, as well as IL-1β, IL-6 and IL-18, whereas protein expression in the Nrf2 pathway was significantly changed. Inhibition of NF-κB or NLRP3 significantly decreased expression of IL-1β and IL-18 proteins in mMECs infected with P. bovis. Additionally, activating Nrf2 inhibited expression of NLRP3 and IL-1β. In conclusion, P. bovis induced an inflammatory response via the NF-κB/NLRP3 inflammasome pathway; however, scavenging ROS or activating Nrf2 mitigated the inflammatory response in infected mMECs.
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http://dx.doi.org/10.1016/j.freeradbiomed.2022.04.005DOI Listing
May 2022

Asymmetric inverse-electron-demand 1,3-dipolar cycloadditions of cyclopentadienones and thiophene-1,1-dioxide with ,-cyclic azomethine imines.

Chem Commun (Camb) 2022 May 3;58(36):5502-5505. Epub 2022 May 3.

Key Laboratory of Drug-Targeting and Drug Delivery System of Education Ministry and Sichuan province, and Sichuan Research Center for Drug Precision Industrial Technology, West China School of Pharmacy, Sichuan University, Chengdu 610041, China.

The normal 1,3-dipolar cycloaddition between the carbonates of 4-hydroxy-2-cyclopentenones and ,-cyclic azomethine imines can be switched to an inverse-electron-demand version under Pd(0) catalysis, by generation of HOMO-raised -Pd(0)-cyclopentadienone complexes. An array of fused heterocyclic architectures are constructed with high levels of diastereo and enantioselectivity, and diastereodivergent synthesis is well realised by tuning the bifunctional phosphine ligands. In addition, similar reaction with formed thiophene-1,1-dioxide is compatible by using a chiral bisphosphine ligand, and the fused cyclic sulfone frameworks are afforded with high stereoselectivity.
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http://dx.doi.org/10.1039/d2cc01103dDOI Listing
May 2022

Targeting regulated cell death (RCD) with small-molecule compounds in triple-negative breast cancer: a revisited perspective from molecular mechanisms to targeted therapies.

J Hematol Oncol 2022 04 12;15(1):44. Epub 2022 Apr 12.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, and West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.

Triple-negative breast cancer (TNBC) is a subtype of human breast cancer with one of the worst prognoses, with no targeted therapeutic strategies currently available. Regulated cell death (RCD), also known as programmed cell death (PCD), has been widely reported to have numerous links to the progression and therapy of many types of human cancer. Of note, RCD can be divided into numerous different subroutines, including autophagy-dependent cell death, apoptosis, mitotic catastrophe, necroptosis, ferroptosis, pyroptosis and anoikis. More recently, targeting the subroutines of RCD with small-molecule compounds has been emerging as a promising therapeutic strategy, which has rapidly progressed in the treatment of TNBC. Therefore, in this review, we focus on summarizing the molecular mechanisms of the above-mentioned seven major RCD subroutines related to TNBC and the latest progress of small-molecule compounds targeting different RCD subroutines. Moreover, we further discuss the combined strategies of one drug (e.g., narciclasine) or more drugs (e.g., torin-1 combined with chloroquine) to achieve the therapeutic potential on TNBC by regulating RCD subroutines. More importantly, we demonstrate several small-molecule compounds (e.g., ONC201 and NCT03733119) by targeting the subroutines of RCD in TNBC clinical trials. Taken together, these findings will provide a clue on illuminating more actionable low-hanging-fruit druggable targets and candidate small-molecule drugs for potential RCD-related TNBC therapies.
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http://dx.doi.org/10.1186/s13045-022-01260-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9006445PMC
April 2022

Catalytic asymmetric [3 + 2] cycloaddition of pyrazolone-derived MBH carbonate: highly stereoselective construction of the bispiro-[pyrazolone-dihydropyrrole-oxindole] skeleton.

Chem Commun (Camb) 2022 Apr 28;58(35):5363-5366. Epub 2022 Apr 28.

State Key Laboratory of Southwestern Chinese Medicine Resources, Hospital of Chengdu University of Traditional Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.

A catalytic asymmetric construction of the bispiro[pyrazolone-dihydropyrrole-oxindole] skeleton catalyzed by chiral DMAP-derived catalyst was successfully achieved by employing recently explored pyrazolone-derived MBH carbonate in high yields with excellent stereoselectivities. The proposed transition state indicated that the intermolecular hydrogen bonds and π-π interactive forces played an essential role in stereoselective chemical transformation.
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http://dx.doi.org/10.1039/d2cc00618aDOI Listing
April 2022

Sulphur ylide-mediated cyclopropanation and subsequent spirocyclopropane rearrangement reactions.

Org Biomol Chem 2022 05 4;20(17):3486-3490. Epub 2022 May 4.

Institute for Advanced Study, Chengdu University, Chengdu 610106, China.

The efficient construction of cyclopropyl spiroindoline skeletons and the exploration of related follow-up synthetic transformations have elicited considerable interest amongst members of the chemistry community. Here, we describe a formal (2 + 1) annulation and three-component (1 + 1 + 1) cascade cyclisation sulphur ylide cyclopropanation under mild conditions. The spiro-cyclopropyl iminoindoline moiety can be readily transformed into another medicinally interesting pyrrolo[3,4-]quinoline framework through a novel rearrangement process.
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http://dx.doi.org/10.1039/d2ob00466fDOI Listing
May 2022

-induced autophagy of bovine mammary epithelial cell PI3K/AKT/mTOR pathway.

J Dairy Res 2022 Apr 7:1-7. Epub 2022 Apr 7.

College of Veterinary Medicine, China Agricultural University, Beijing100193, China.

Streptococcus agalactiae (S. agalactiae) infection is a significant cause of mastitis, resulting in loss of cellular homeostasis and tissue damage. Autophagy plays an essential function in cell survival, defense, and the preservation of cellular homeostasis, and is often part of the response to pathogenic challenge. However, the effect of autophagy induced by S. agalactiae in bovine mammary epithelial cells (bMECs) is mainly unknown. So in this study, an intracellular S. agalactiae infection model was established. Through evaluating the autophagy-related indicators, we observed that after S. agalactiae infection, a significant quantity of LC3-I was converted to LC3-II, p62 was degraded, and levels of Beclin1 and Bcl2 increased significantly in bMECs, indicating that S. agalactiae induced autophagy. The increase in levels of LAMP2 and LysoTracker Deep Red fluorescent spots indicated that lysosomes had participated in the degradation of autophagic contents. After autophagy was activated by rapamycin (Rapa), the amount of p-Akt and p-mTOR decreased significantly, whilst the amount of intracellular S. agalactiae increased significantly. Whereas the autophagy was inhibited by 3-methyladenine (3MA), the number of intracellular pathogens decreased. In conclusion, the results demonstrated that S. agalactiae could induce autophagy through PI3K/Akt/mTOR pathway and utilize autophagy to survive in bMECs.
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http://dx.doi.org/10.1017/S0022029922000243DOI Listing
April 2022

PPFIA4 promotes castration-resistant prostate cancer by enhancing mitochondrial metabolism through MTHFD2.

J Exp Clin Cancer Res 2022 Apr 5;41(1):125. Epub 2022 Apr 5.

The Key Laboratory of Experimental Teratology, Ministry of Education and Department of Pathology, School of Basic Medical Sciences, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Background: The development of castration-resistant prostate cancer (CRPC) remains a major obstacle in the treatment of prostate cancer (PCa). Dysregulated mitochondrial function has been linked to the initiation and progression of diverse human cancers. Deciphering the novel molecular mechanisms underlying mitochondrial function may provide important insights for developing novel therapeutics for CRPC.

Methods: We investigate the expression of the protein tyrosine phosphatase receptor type F polypeptide interacting protein alpha 4 (PPFIA4) using public datasets and tumor specimens from PCa cases by immunohistochemistry. Gain- and loss-of-function studies are performed in PCa cell lines and mouse models of subcutaneous xenograft to characterize the role of PPFIA4 in CRPC. Gene expression regulation is evaluated by a series of molecular and biochemical experiments in PCa cell lines. The therapeutic effects of methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) inhibitor combined enzalutamide are assessed using in vitro functional assays and in vivo mouse models.

Results: We show that the increase of PPFIA4 exacerbates aggressive phenotype resembling CRPC. A fraction of PPFIA4 localizes to mitochondria and interacts with MTHFD2, a key enzyme for one-carbon metabolism. Androgen deprivation increases the translocation of PPFIA4 into mitochondria and increases the interaction between PPFIA4 and MTHFD2, which result in the elevation of tyrosine phosphorylated MTHFD2. Consequently, the levels of NADPH synthesis increase, resulting in protection against androgen deprivation-induced mitochondrial dysfunction, as well as promotion of tumor growth. Clinically, PPFIA4 expression is significantly increased in CRPC tissues compared with localized PCa ones. Importantly, an MTHFD2 inhibitor, DS18561882, combined with enzalutamide can significantly inhibit CRPC cell proliferation in vitro and tumor growth in vivo.

Conclusion: Overall, our findings reveal a PPFIA4-MTHFD2 complex in mitochondria that links androgen deprivation to mitochondrial metabolism and mitochondrial dysfunction, which suggest a potential strategy to inhibit CRPC progression.
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http://dx.doi.org/10.1186/s13046-022-02331-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8985307PMC
April 2022

Radical Acylalkylation of 1,3-Enynes To Access Allenic Ketones via -Heterocyclic Carbene Organocatalysis.

J Org Chem 2022 04 29;87(8):5229-5241. Epub 2022 Mar 29.

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, P. R. China.

An -heterocyclic carbene organocatalytic 1,4-difunctionalization of 1,3-enynes was developed. This organocatalytic strategy was suitable for a broad spectrum of substrates to efficiently synthesize allenic ketones bearing diverse substituents. Preliminary mechanistic studies suggest a radical reaction pathway for this organocatalytic acylalkylation process.
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http://dx.doi.org/10.1021/acs.joc.2c00037DOI Listing
April 2022

Identification of Alternative Splicing Events Associated with Paratuberculosis in Dairy Cattle Using Multi-Tissue RNA Sequencing Data.

Genes (Basel) 2022 03 11;13(3). Epub 2022 Mar 11.

National Engineering Laboratory of Animal Breeding, Department of Animal Genetics and Breeding, College of Animal Science and Technology, China Agricultural University, Beijing 100193, China.

Paratuberculosis is a major endemic disease caused by (MAP) infection and leads to huge economic loss in the dairy sector worldwide. Alternative splicing (AS) events, playing indispensable regulatory roles in many protein functions and biological pathways, are shown to be associated with complex traits and diseases. In this study, by integrating the RNA sequencing (RNA-seq) data of 24 samples from three tissues (peripheral blood, jejunum and salivary gland) of Holstein cows, we obtained 2,706,541,696 uniquely mapped reads in total that represented 12,870 expressed genes, and detected 4285 differentially expressed genes (DEGs) between MAP-infected and healthy cows ( < 0.05). Of them, 92 differentially expressed splicing factors (DESFs) were included. Further, 119, 150 and 68 differential alternative splicing (DAS) events between MAP-infected and healthy cows were identified in peripheral blood, jejunum and salivary glands, respectively. Of note, six DAS events were highly and significantly correlated with the DESFs ( > 0.9; < 0.01), and their corresponding genes ( (), (), (), (), () and ()) were significantly enriched in immune response such as vesicle-mediated transport, regulation of acute inflammatory response and tuberculosis through gene ontology (GO) and KEGG analysis. KS test showed that the DAS events in the and genes indeed displayed differences between MAP-infected cows and healthy cows. The DAS in might produce a new protein sequence with lack of 23 amino acids, and the DAS in induced a stop codon of premature occurrence and resulted in a lack of functional domain. In summary, this study identified the DAS events and corresponding genes related to MAP-infection base on the RNA-seq data from multiple tissues of Holstein cows, providing novel insights into the regulatory mechanisms underpinning paratuberculosis in dairy cattle.
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http://dx.doi.org/10.3390/genes13030497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8948961PMC
March 2022

Advances in indole-containing alkaloids as potential anticancer agents by regulating autophagy.

Biomed Pharmacother 2022 May 19;149:112827. Epub 2022 Mar 19.

State Key Laboratory of Southwestern Chinese Medicine Resources, Hospital of Chengdu University of Traditional Chinese Medicine, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China. Electronic address:

Cancer is a leading cause of death worldwide, and cancer development is often associated with disturbances in the autophagy process. Autophagy is a catabolic process involved in many physiological processes, crucial for cell growth and survival. It is an intracellular lysosomal/vacuolar degradation system. In this system, inner cytoplasmic cell membrane is degraded by lysosomal hydrolases, and the products are released back into the cytoplasm. Indole alkaloids are natural products extensively found in nature and have been proven to possess various pharmacological activities. In recent years, pharmacological studies have demonstrated another potential of indole alkaloids, autophagy regulation. The regulation may contribute to the efficacy of indole alkaloids in preventing and treating cancer. This review summarizes the current understanding of indole alkaloids' effect on tumor cells and autophagy. Then, we focus on mechanisms by which indole alkaloids can target the autophagy process associated with cancer, including the PI3K/Akt/mTOR signaling pathway, MAPK signaling pathway, ROS signaling pathway, Beclin-1, and so on. Literature has been surveyed primarily from 2009 to Nov. 2021, and some semisynthetic or fully synthetic indole derivatives are also discussed.
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http://dx.doi.org/10.1016/j.biopha.2022.112827DOI Listing
May 2022

Fatty acid desaturase 2 affects the milk-production traits in Chinese Holsteins.

Anim Genet 2022 Jun 15;53(3):422-426. Epub 2022 Mar 15.

Department of Animal Genetics and Breeding, College of Animal Science and Technology, Key Laboratory of Animal Genetics, Breeding and Reproduction of Ministry of Agriculture and Rural Affairs, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, China.

As a member of the fatty acid desaturase family, fatty acid desaturase 2 (FADS2) gene is a rate-limiting enzyme in the synthesis of unsaturated fatty acids and within/near to the reported QTL regions for milk-production traits. We previously found that FADS2 is differentially expressed during different lactations of Chinese Holstein cows, and participates in lipid metabolic processes by influencing the insulin, PI3K-Akt, MAPK, AMPK, mTOR and PPAR signaling pathways. Therefore, we considered this gene as a candidate gene for milk-production traits. In this study, we identified 12 SNPs in FADS2 by re-sequencing, including two SNPs in the 5' flanking region, one in the seventh exon, five in introns, two in the 3' untranslated region and two in the 3' flanking region. The 29:g.40378819C>T is a missense mutation that causes alanine (GCG) to be replaced with valine (GTG). Through single marker association analysis, we found that all of the 12 SNPs were significantly associated with 305 day milk yield, fat yield, fat percentage, protein yield or protein percentage (p < 0.0493). The results of the subsequent haplotype association analysis also confirmed the associations between the gene and milk-production traits. In summary, this study suggests that there is a significant genetic association between FADS2 and milk-production traits, and that the SNPs with significant genetic effects can provide important molecular information for the development of a genomic selection chip in dairy cattle.
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http://dx.doi.org/10.1111/age.13192DOI Listing
June 2022

Source emission and attribution of a large airport in Central China.

Sci Total Environ 2022 Jul 12;829:154519. Epub 2022 Mar 12.

Research Centre for Environment and Sustainable Development of Civil Aviation Administration of China, Civil Aviation University of China, Tianjin, China.

Large airport operation release harmful air pollutants and have adverse impact on local air quality. As one of the world's top 30 busiest airports, Xinzheng International Airport (CGO) located in Zhengzhou City, China, its emission impacts needs particular attention. To identify the possible impacts and quantify the contribution of CGO airport to air pollution, a comprehensive approach including emission inventory, continuous monitoring, coupled with statistical modelling was adopted in this study. We estimated a more detailed emissions inventory for CGO, including hourly and annual emissions from engines and auxiliary power units of aircrafts during landing and take-off flight, and airside ground support equipment (GSE) in 2019. The results indicate that almost all the CGO specific parameters including operating hours, fuel consumption and unit LTO emissions at different modes were lower than ICAO reference values. The annual total emissions of NO, CO, HC, SO and PM from CGO from aircrafts and GSE were 1207.7, 921.3, 123.7, 268.3 and 36.2 tons, respectively. In addition to SO, the main engines of the aircraft accounted for 80.3%, 62.6%, 45.5% and 74.3% of the total emissions, respectively. Meanwhile, a continuous monitoring campaign was conducted for one year in the vicinity of CGO airport. The monitoring data were analyzed using generalized additive model (GAM) to quantify the impact of NO emissions from airport activities on air quality at CGO. The results showed that even the influence of environmental and meteorological variables was greater, nearly 13% of the ambient NO concentrations were explained by emissions from airport activities, indicating the importance of airport-related emissions as the major source affecting local air quality.
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http://dx.doi.org/10.1016/j.scitotenv.2022.154519DOI Listing
July 2022
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