Publications by authors named "Kun Han"

180 Publications

Endothelial cell infection and dysfunction, immune activation in severe COVID-19.

Theranostics 2021 6;11(16):8076-8091. Epub 2021 Jul 6.

Tulane National Primate Research Center, Covington, LA 70433, USA.

: Pulmonary vascular endotheliitis, perivascular inflammation, and immune activation are observed in COVID-19 patients. While the initial SARS-CoV-2 infection mainly infects lung epithelial cells, whether it also infects endothelial cells (ECs) and to what extent SARS-CoV-2-mediated pulmonary vascular endotheliitis is associated with immune activation remain to be determined. : To address these questions, we studied SARS-CoV-2-infected () mice, a severe COVID-19 mouse model, as well as lung samples from SARS-CoV-2-infected nonhuman primates (NHP) and patient deceased from COVID-19. We used immunostaining, RNAscope, and electron microscopy to analyze the organs collected from animals and patient. We conducted bulk and single cell (sc) RNA-seq analyses, and cytokine profiling of lungs or serum of the severe COVID-19 mice. : We show that SARS-CoV-2-infected mice develop severe COVID-19, including progressive body weight loss and fatality at 7 days, severe lung interstitial inflammation, edema, hemorrhage, perivascular inflammation, systemic lymphocytopenia, and eosinopenia. Body weight loss in mice correlated with the severity of pneumonia, but not with brain infection. We also observed endothelial activation and dysfunction in pulmonary vessels evidenced by the up-regulation of VCAM1 and ICAM1 and the downregulation of VE-cadherin. We detected SARS-CoV-2 in capillary ECs, activation and adhesion of platelets and immune cells to the vascular wall of the alveolar septa, and increased complement deposition in the lungs, in both COVID-19-murine and NHP models. We also revealed that pathways of coagulation, complement, K-ras signaling, and genes of ICAM1 and VCAM1 related to EC dysfunction and injury were upregulated, and were associated with massive immune activation in the lung and circulation. : Together, our results indicate that SARS-CoV-2 causes endotheliitis via both infection and infection-mediated immune activation, which may contribute to the pathogenesis of severe COVID-19 disease.
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http://dx.doi.org/10.7150/thno.61810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315069PMC
August 2021

SARS-CoV-2 Infects Endothelial Cells and .

Front Cell Infect Microbiol 2021 6;11:701278. Epub 2021 Jul 6.

Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, United States.

SARS-CoV-2 infection can cause fatal inflammatory lung pathology, including thrombosis and increased pulmonary vascular permeability leading to edema and hemorrhage. In addition to the lung, cytokine storm-induced inflammatory cascade also affects other organs. SARS-CoV-2 infection-related vascular inflammation is characterized by endotheliopathy in the lung and other organs. Whether SARS-CoV-2 causes endotheliopathy by directly infecting endothelial cells is not known and is the focus of the present study. We observed 1) the co-localization of SARS-CoV-2 with the endothelial cell marker CD31 in the lungs of SARS-CoV-2-infected mice expressing hACE2 in the lung by intranasal delivery of adenovirus 5-hACE2 (Ad5-hACE2 mice) and non-human primates at both the protein and RNA levels, and 2) SARS-CoV-2 proteins in endothelial cells by immunogold labeling and electron microscopic analysis. We also detected the co-localization of SARS-CoV-2 with CD31 in autopsied lung tissue obtained from patients who died from severe COVID-19. Comparative analysis of RNA sequencing data of the lungs of infected Ad5-hACE2 and Ad5-empty (control) mice revealed upregulated KRAS signaling pathway, a well-known pathway for cellular activation and dysfunction. Further, we showed that SARS-CoV-2 directly infects mature mouse aortic endothelial cells (AoECs) that were activated by performing an aortic sprouting assay prior to exposure to SARS-CoV-2. This was demonstrated by co-localization of SARS-CoV-2 and CD34 by immunostaining and detection of viral particles in electron microscopic studies. Moreover, the activated AoECs became positive for ACE-2 but not quiescent AoECs. Together, our results indicate that in addition to pneumocytes, SARS-CoV-2 also directly infects mature vascular endothelial cells and , which may contribute to cardiovascular complications in SARS-CoV-2 infection, including multipleorgan failure.
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http://dx.doi.org/10.3389/fcimb.2021.701278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8292147PMC
July 2021

Grass carp (Ctenopharyngodon idella) interferon regulatory factor 8 down-regulates interferon1 expression via interaction with interferon regulatory factor 2 in vitro.

Mol Immunol 2021 09 16;137:202-211. Epub 2021 Jul 16.

School of Life Science, Nanchang University, Nanchang, 330031, China. Electronic address:

Interferon regulatory factor 8 (IRF8), also known as interferon consensus sequence-binding protein (ICSBP), is a negative regulatory factor of interferon (IFN) and plays an important role in cell differentiation and innate immunity in mammals. In recent years, some irf8 homologous genes have been cloned and confirmed to take part in innate immune response in fish, but the mechanism still remains unclear. In this paper, a grass carp (Ctenopharyngodon idella) irf8 gene (Ciirf8) was cloned and characterized. The deduced protein (CiIRF8) possesses a highly conserved N-terminal DNA binding domain but a less well-conserved C-terminal IRF association domain (IAD). Ciirf8 was widely expressed in all tested tissues of grass carp and up-regulated following poly(I:C) stimulation. Ciirf8 expression was also up-regulated in CIK cells upon treatment with poly(I:C). To explore the molecular mechanism of how fish IRF8 regulates ifn1 expression, the similarities and differences of grass carp IRF8 and IRF2 were compared and contrasted. Subcellular localization analysis showed that CiIRF8 is located both in the cytoplasm and nucleus; however, CiIRF2 is only located in the nucleus. The nuclear-cytoplasmic translocation of CiIRF8 was observed in CIK cells under stimulation with poly(I:C). The interaction of CiIRF8 and CiIRF2 was further confirmed by a co-immunoprecipitation assay in the nucleus. Dual-luciferase reporter assays showed that the promoter activity of Ciifn1 was significantly inhibited by co-transfection with CiIRF2 and CiIRF8. The transcription inhibition of Ciifn1 was alleviated by competitive binding of CiIRF2 and CiIRF8 to CiIRF1. In conclusion, CiIRF8 down-regulates Ciifn1 expression via interaction with CiIRF2 in cells.
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http://dx.doi.org/10.1016/j.molimm.2021.04.020DOI Listing
September 2021

Dose-Dependent Pattern of Cochlear Synaptic Degeneration in C57BL/6J Mice Induced by Repeated Noise Exposure.

Neural Plast 2021 9;2021:9919977. Epub 2021 Jun 9.

Department of Otolaryngology-Head and Neck Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200011, China.

It is widely accepted that even a single acute noise exposure at moderate intensity that induces temporary threshold shift (TTS) can result in permanent loss of ribbon synapses between inner hair cells and afferents. However, effects of repeated or chronic noise exposures on the cochlear synapses especially medial olivocochlear (MOC) efferent synapses remain elusive. Based on a weeklong repeated exposure model of bandwidth noise over 2-20 kHz for 2 hours at seven intensities (88 to 106 dB SPL with 3 dB increment per gradient) on C57BL/6J mice, we attempted to explore the dose-response mechanism of prolonged noise-induced audiological dysfunction and cochlear synaptic degeneration. In our results, mice repeatedly exposed to relatively low-intensity noise (88, 91, and 94 dB SPL) showed few changes on auditory brainstem response (ABR), ribbon synapses, or MOC efferent synapses. Notably, repeated moderate-intensity noise exposures (97 and 100 dB SPL) not only caused hearing threshold shifts and the inner hair cell ribbon synaptopathy but also impaired MOC efferent synapses, which might contribute to complex patterns of damages on cochlear function and morphology. However, repeated high-intensity (103 and 106 dB SPL) noise exposures induced PTSs mainly accompanied by damages on cochlear amplifier function of outer hair cells and the inner hair cell ribbon synaptopathy, rather than the MOC efferent synaptic degeneration. Moreover, we observed a frequency-dependent vulnerability of the repeated acoustic trauma-induced cochlear synaptic degeneration. This study provides a sight into the hypothesis that noise-induced cochlear synaptic degeneration involves both afferent (ribbon synapses) and efferent (MOC terminals) pathology. The pattern of dose-dependent pathological changes induced by repeated noise exposure at various intensities provides a possible explanation for the complicated cochlear synaptic degeneration in humans. The underlying mechanisms remain to be studied in the future.
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http://dx.doi.org/10.1155/2021/9919977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8211526PMC
June 2021

Retinoblastoma tumor suppressor gene 1 enhances 5-Fluorouracil chemosensitivity through SDF-1/CXCR4 axis by regulating autophagy in gastric cancer.

Pathol Res Pract 2021 Aug 21;224:153532. Epub 2021 Jun 21.

Department of Gastroenterology, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710004, China. Electronic address:

Due to lack of effective biomarkers for early diagnosis, most patients are diagnosed with advanced gastric cancer and have lower survival rates. 5-Fluorouracil (5-FU) is one of commonly used drugs for chemotherapy of gastric cancer, but drug resistance limits the wide application of agents. Retinoblastoma tumor suppressor gene 1 (RB1) is a key regulator in the progression of various human cancers, including gastric cancer. However, the effects of RB1 on chemosensitivity and the underlying mechanisms in gastric cancer (GC) are not clear. In this study, expressions of RB1 in GC cell lines were evaluated by RT-qPCR and western blot assay. CCK-8 was applied to examine the effect of 5-FU on cell viability. Meanwhile, IC50 values were calculated. The drug-resistance protein MDR1 and autophagy-related proteins were detected by western blot assay. Flow cytometry was used to detect cell cycle. The results showed that RB1 expressions were downregulated in GC cell lines and had significant differences between 5-FU resistance cell lines (SNU-620/5-FU and NUGC-3/5-FU) and non-resistance cell lines (SNU-620 and NUGC-3). Overexpression of RB1 enhanced 5-FU sensitivity of GC cells and caused cell cycle arrest in the S phase. Meanwhile, autophagy-related proteins were downregulated. Mechanistically, SDF-1/CXCR4 participated in the regulation of RB1 on cell autophagy. Autophagy activator, SDF-1 treatment and CXCR4 activation reversed the promoted effects of RB1 on 5-FU sensitivity in GC cells. In conclusion, our data revealed that RB1 was downregulated in GC cell lines. RB1 overexpression enhanced 5-FU chemosensitivity in GC cells by regulating cell autophagy via SDF-1/CXCR4 pathway. RB1 might serve as a promising therapeutic target of GC.
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http://dx.doi.org/10.1016/j.prp.2021.153532DOI Listing
August 2021

A deep learning-based auto-segmentation system for organs-at-risk on whole-body computed tomography images for radiation therapy.

Radiother Oncol 2021 07 4;160:175-184. Epub 2021 May 4.

Department of Radiation Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address:

Background And Purpose: Delineating organs at risk (OARs) on computed tomography (CT) images is an essential step in radiation therapy; however, it is notoriously time-consuming and prone to inter-observer variation. Herein, we report a deep learning-based automatic segmentation (AS) algorithm (WBNet) that can accurately and efficiently delineate all major OARs in the entire body directly on CT scans.

Materials And Methods: We collected 755 CT scans of the head and neck, thorax, abdomen, and pelvis and manually delineated 50 OARs on the CT images. The CT images with contours were split into training and test sets consisting of 505 and 250 cases, respectively, to develop and validate WBNet. The volumetric Dice similarity coefficient (DSC) and 95th-percentile Hausdorff distance (95% HD) were calculated to evaluate delineation quality for each OAR. We compared the performance of WBNet with three AS algorithms: one commercial multi-atlas-based automatic segmentation (ABAS) software, and two deep learning-based AS algorithms, namely, AnatomyNet and nnU-Net. We have also evaluated the time saving and dose accuracy of WBNet.

Results: WBNet achieved average DSCs of 0.84 and 0.81 on in-house and public datasets, respectively, which outperformed ABAS, AnatomyNet, and nnU-Net. WBNet could reduce the delineation time significantly and perform well in treatment planning, with clinically acceptable dose differences compared with those in manual delineation.

Conclusion: This study shows the feasibility and benefits of using WBNet in clinical practice.
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http://dx.doi.org/10.1016/j.radonc.2021.04.019DOI Listing
July 2021

Metagenomic sequencing reveals viral abundance and diversity in mosquitoes from the Shaanxi-Gansu-Ningxia region, China.

PLoS Negl Trop Dis 2021 04 26;15(4):e0009381. Epub 2021 Apr 26.

Chinese Center for Disease Control and Prevention -Wuhan Institute of Virology, Chinese Academy of Sciences Joint Research Center for Emerging Infectious Diseases and Biosafety, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, People's Republic of China.

Background: Mosquitoes host and transmit numerous arthropod-borne viruses (arboviruses) that cause disease in both humans and animals. Effective surveillance of virome profiles in mosquitoes is vital to the prevention and control of mosquito-borne diseases in northwestern China, where epidemics occur frequently.

Methods: Mosquitoes were collected in the Shaanxi-Gansu-Ningxia region (Shaanxi Province, Gansu Province, and Ningxia Hui Autonomous Region) of China from June to August 2019. Morphological methods were used for taxonomic identification of mosquito species. High-throughput sequencing and metagenomic analysis were used to characterize mosquito viromes.

Results: A total of 22,959 mosquitoes were collected, including Culex pipiens (45.7%), Culex tritaeniorhynchus (40.6%), Anopheles sinensis (8.4%), Aedes (5.2%), and Armigeres subalbatus (0.1%). In total, 3,014,183 (0.95% of clean reads) viral sequences were identified and assigned to 116 viral species (including pathogens such as Japanese encephalitis virus and Getah virus) in 31 viral families, including Flaviviridae, Togaviridae, Phasmaviridae, Phenuiviridae, and some unclassified viruses. Mosquitoes collected in July (86 species in 26 families) showed greater viral diversity than those from June and August. Culex pipiens (69 species in 25 families) and Culex tritaeniorhynchus (73 species in 24 families) carried more viral species than Anopheles sinensis (50 species in 19 families) or Aedes (38 species in 20 families) mosquitoes.

Conclusion: Viral diversity and abundance were affected by mosquito species and collection time. The present study elucidates the virome compositions of various mosquito species in northwestern China, improving the understanding of virus transmission dynamics for comparison with those of disease outbreaks.
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http://dx.doi.org/10.1371/journal.pntd.0009381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101993PMC
April 2021

Audiometric Phenotypes of Noise-Induced Hearing Loss by Data-Driven Cluster Analysis and Their Relevant Characteristics.

Front Med (Lausanne) 2021 25;8:662045. Epub 2021 Mar 25.

Department of Otolaryngology-Head and Neck Surgery, Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

The definition of notched audiogram for noise-induced hearing loss (NIHL) is presently based on clinical experience, but audiometric phenotypes of NIHL are highly heterogeneous. The data-driven clustering of subtypes could provide refined characteristics of NIHL, and help identify individuals with typical NIHL at diagnosis. This cross-sectional study initially recruited 12,218 occupational noise-exposed employees aged 18-60 years from two factories of a shipyard in Eastern China. Of these, 10,307 subjects with no history of otological injurie or disease, family history of hearing loss, or history of ototoxic drug use were eventually enrolled. All these subjects completed health behavior questionnaires, cumulative noise exposure (CNE) measurement, and pure-tone audiometry. We did data-driven cluster analysis (k-means clustering) in subjects with hearing loss audiograms ( = 6,599) consist of two independent datasets ( = 4,461 and = 2,138). Multinomial logistic regression was performed to analyze the relevant characteristics of subjects with different audiometric phenotypes compared to those subjects with normal hearing audiograms ( = 3,708). A total of 10,307 subjects (9,165 males [88.9%], mean age 34.5 [8.8] years, mean CNE 91.2 [22.7] dB[A]) were included, 3,708 (36.0%) of them had completely normal hearing, the other 6,599 (64.0%) with hearing loss audiograms were clustered into four audiometric phenotypes, which were replicable in two distinct datasets. We named the four clusters as the 4-6 kHz sharp-notched, 4-6 kHz flat-notched, 3-8 kHz notched, and 1-8 kHz notched audiogram. Among them, except for the 4-6 kHz flat-notched audiogram which was not significantly related to NIHL, the other three phenotypes with different relevant characteristics were strongly associated with noise exposure. In particular, the 4-6 kHz sharp-notched audiogram might be a typical subtype of NIHL. By data-driven cluster analysis of the large-scale noise-exposed population, we identified three audiometric phenotypes associated with distinct NIHL subtypes. Data-driven sub-stratification of audiograms might eventually contribute to the precise diagnosis and treatment of NIHL.
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http://dx.doi.org/10.3389/fmed.2021.662045DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8027076PMC
March 2021

Enhanced Metal-Insulator Transition in Freestanding VO Down to 5 nm Thickness.

ACS Appl Mater Interfaces 2021 Apr 1;13(14):16688-16693. Epub 2021 Apr 1.

Division of Physics and Applied Physics, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, 637371, Singapore.

Ultrathin freestanding membranes with a pronounced metal-insulator transition (MIT) have huge potential for future flexible electronic applications as well as provide a unique aspect for the study of lattice-electron interplay. However, the reduction of the thickness to an ultrathin region (a few nm) is typically detrimental to the MIT in epitaxial films, and even catastrophic for their freestanding form. Here, we report an enhanced MIT in VO-based freestanding membranes, with a lateral size up to millimeters and the VO thickness down to 5 nm. The VO membranes were detached by dissolving a SrAlO sacrificial layer between the VO thin film and the -AlO(0001) substrate, allowing the transfer onto arbitrary surfaces. Furthermore, the MIT in the VO membrane was greatly enhanced by inserting an intermediate AlO buffer layer. In comparison with the best available ultrathin VO membranes, the enhancement of MIT is over 400% at a 5 nm VO thickness and more than 1 order of magnitude for VO above 10 nm. Our study widens the spectrum of functionality in ultrathin and large-scale membranes and enables the potential integration of MIT into flexible electronics and photonics.
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http://dx.doi.org/10.1021/acsami.1c01581DOI Listing
April 2021

[email protected] Heterostructure as Robust Lithiophilicity and Sulfiphilicity Mediator toward High-Rate and Long-Life Lithium-Sulfur Batteries.

ACS Nano 2021 Apr 25;15(4):7114-7130. Epub 2021 Mar 25.

The Education Ministry Key Lab of Resource Chemistry, Shanghai Key Laboratory of Rare Earth Functional Materials, College of Chemistry and Materials Science, Shanghai Normal University, Shanghai 200234, China.

Lithium-sulfur (Li-S) batteries are severely hindered by the low sulfur utilization and short cycling life, especially at high rates. One of the effective solutions to address these problems is to improve the sulfiphilicity of lithium polysulfides (LiPSs) and the lithiophilicity of the lithium anode. However, it is a great challenge to simultaneously optimize both aspects. Herein, by incorporating the merits of strong absorbability and high conductivity of SnS with good catalytic capability of ZnS, a ZnS-SnS heterojunction coated with a polydopamine-derived N-doped carbon shell (denoted as [email protected]) with uniform cubic morphology was obtained and compared with the [email protected] heterostructure and its single-component counterparts ([email protected] and [email protected]). Theoretical calculations, XANES, and Raman spectrum were utilized to elucidate rapid anchoring-diffusion-transformation of LiPSs, inhibition of the shuttling effect, and improvement of the sulfur electrochemistry of bimetal ZnS-SnS heterostructure at the molecular level. When applied as a modification layer coated on the separator, the [email protected] cell with optimized lithiophilicity and sulfiphilicity enables desirable sulfur electrochemistry, including high reversibility of 1149 mAh g for 300 cycles at 0.2 C, high rate performance of 661 mAh g at 10 C, and long cycle life with a low fading rate of 0.0126% each cycle after 2000 cycles at 4 C. Furthermore, a favorable areal capacity of 8.27 mAh cm is maintained under high sulfur mass loading of 10.3 mg cm. This work furnishes a feasible scheme to the rational design of bimetal sulfides heterostructures and boosts the development of other electrochemical applications.
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http://dx.doi.org/10.1021/acsnano.1c00270DOI Listing
April 2021

Development of a TaqMan loop-mediated isothermal amplification assay for the rapid detection of pigeon paramyxovirus type 1.

Arch Virol 2021 Jun 23;166(6):1599-1605. Epub 2021 Mar 23.

Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

Pigeon paramyxovirus-1 (PPMV-1) is a strain of Newcastle disease virus (NDV) that has adapted to infect pigeons and poses a constant threat to the commercial poultry industry. Early detection via rapid and sensitive methods, along with timely preventative and mitigating actions, is important for reducing the spread of PPMV-1. Here, we report the development of a TaqMan loop-mediated isothermal amplification assay (TaqMan-LAMP) for rapid and specific detection of PPMV-1 based on the F gene. This system makes use of six novel primers and a TaqMan probe that targets nine distinct regions of the F gene that are highly conserved among PPMV-1 isolates. The results showed that the limit of detection was 10 copies μL for PPMV-1 cDNA and 0.1 ng for PPMV-1 RNA. The reaction was completed within 25 min and was thus faster than conventional RT-PCR. Moreover, no cross-reactions with similar viruses or with peste des petits ruminants virus (PPRV) or NDV LaSota vaccine strains were observed under the same conditions. To evaluate the applicability of the assay, the TaqMan-LAMP assay and a commercial RT-PCR assay were compared using 108 clinical samples, and the concordance rate between two methods was found to be 96.3%. The newly developed PPMV-1 TaqMan-LAMP assay can therefore be used for simple, efficient, rapid, specific, and sensitive diagnosis of PPMV-1 infections.
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http://dx.doi.org/10.1007/s00705-021-04963-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7986176PMC
June 2021

Sex differences in noise-induced hearing loss: a cross-sectional study in China.

Biol Sex Differ 2021 03 6;12(1):24. Epub 2021 Mar 6.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, 639 ZhiZaoJu Road, HuangPu District, Shanghai, 200011, People's Republic of China.

Background: Significant sex differences exist in hearing physiology, while few human studies have investigated sex differences in noise-induced hearing loss (NIHL), and the sex bias in previous studies resulted in inadequate female data. The study aims to investigate sex differences in the characteristics of NIHL to provide insight into sex-specific risk factors, prevention strategies and treatment for NIHL.

Methods: This cross-sectional study included 2280 industrial noise-exposed shipyard workers (1140 males and 1140 females matched for age, job and employment length) in China. Individual noise exposure levels were measured to calculate the cumulative noise exposure (CNE), and an audiometric test was performed by an experienced technician in a soundproof booth. Sex differences in and influencing factors of low-frequency (LFHL) and high-frequency hearing loss (HFHL) were analyzed using logistic regression models stratified by age and CNE.

Results: At comparable noise exposure levels and ages, the prevalence of HFHL was significantly higher in males (34.4%) than in females (13.8%), and males had a higher prevalence of HFHL (OR = 4.19, 95% CI 3.18 to 5.52) after adjusting for age, CNE, and other covariates. Sex differences were constant and highly remarkable among subjects aged 30 to 40 years and those with a CNE of 80 to 95 dB(A). Alcohol consumption might be a risk factor for HFHL in females (OR = 3.12, 95% CI 1.10 to 8.89).

Conclusions: This study indicates significant sex differences in NIHL. Males are at higher risk of HFHL than females despite equivalent noise exposure and age. The risk factors for NIHL might be different in males and females.
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http://dx.doi.org/10.1186/s13293-021-00369-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7937304PMC
March 2021

Confining Pyrrhotite Fe S in Carbon Nanotubes Covalently Bonded onto 3D Few-Layer Graphene Boosts Potassium-Ion Storage and Full-Cell Applications.

Small 2021 Mar 3;17(12):e2006719. Epub 2021 Mar 3.

Beijing Advanced Innovation Center for Materials Genome Engineering, Institute for Advanced Materials and Technology, University of Science and Technology Beijing, Beijing, 100083, P.R. China.

The pyrrhotite Fe S with mixed Fe-valence possesses high theoretical capacity, high conductivity, low discharge/charge voltage plateaus, and superior redox reversibility but suffers from structural degradation upon (de)potassiation process due to severe volume variations. Herein, to conquer this issue, a novel hierarchical architecture of confining nano-Fe S in carbon nanotubes covalently bonded onto 3D few-layer graphene (Fe S @[email protected]) is designed for potassium storage. Notably, CNTs could successfully grow on the surface of 3DFG via a tip-growth model under the catalytic effect of Fe C. Such structure enables the hierarchical confinement of 0D nano-Fe S to 1D CNTs and further 1D CNTs to 3DFG, effectively buffering the volume variations, prohibiting the agglomeration of Fe S nanograins, and boosting the ionic/electronic transportation through the stable and conductive CNTs-grafted 3DFG framework. The as-prepared Fe S @[email protected] electrode delivers an exceptional rate capability (502 mAh g at 50 mA g with 277 mAh g at 1000 mA g ) and an excellent long-term cyclic stability up to 1300 cycles. Besides, the in-situ XRD and ex-situ XPS/HRTEM results first elucidate the highly reversible potassium-storage mechanism of Fe S . Furthermore, the designed potassium full-cell employing Fe S @[email protected] anode and potassium Prussian blue (KPB) cathode delivers a promising energy density of ≈120 Wh kg , demonstrating great application prospects.
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http://dx.doi.org/10.1002/smll.202006719DOI Listing
March 2021

A toehold-mediated strand displacement cascade-based DNA assay method flow cytometry and magnetic separation.

Anal Methods 2021 03;13(8):1013-1018

School of Biomedical Engineering (Suzhou), Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230026, China and Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, P. R. China.

Sensitive assay of EGFR T790M, a circulating tumor DNA marker in non-small-cell carcinoma, provides critical information for the decision of clinical treatments, evaluation of radiotherapy effect, and monitoring the progress of recurrence and metastasis. In this report, a novel flow cytometry-based sensing method is proposed for detecting T790M. The toehold-sequence hybridizes with the biotin-labeled initiator sequence and forms IT-dsDNA. The presence of a target induces the displacement of initiator-sequence from IT-dsDNA. The targets are continuously set free with the aid of a helper hairpin sequence for the next cycle. In tandem, the free initiator sequence starts the hybridization chain reaction, which binds the serial of fluorescence-labeled probe sequences. The products of the hybridization chain reaction are captured and separated by magnetic beads, which are finally assayed via flow cytometry. The capability to distinguish single-nucleotide polymorphism and the tolerance of complex matrix in blood serum indicate that this strategy has the promising potential to be applied in the liquid biopsy of clinical samples.
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http://dx.doi.org/10.1039/d0ay02102dDOI Listing
March 2021

Down-Regulation of PDCD4 Promotes Proliferation, Angiogenesis and Tumorigenesis in Glioma Cells.

Front Cell Dev Biol 2020 12;8:593685. Epub 2020 Nov 12.

Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.

The programmed cell death 4 () tumor-suppressor gene regulates cell apoptosis, protein translation, signal transduction, and induction of mediators of inflammation. However, the mechanism by which is down-regulated and regulates tumor growth remains elusive. In this study, we showed that PDCD4 is down-regulated in glioma cells and acts as a tumor suppressor. Based on the TCGA data, we confirmed that AKT2, but not AKT1 or AKT3, interacts with PDCD4, thus leading to the suppression of PDCD4 in glioma cells. Moreover, the analysis suggested that PDCD4 regulates the expression of IL-5, CCL-5, VEGF, and CXCL10 via the NF-kB pathway. Additionally, depletion of levels of promoted angiogenic activity of glioma cells via the VEGF-STAT3 pathway. When tumor cells over-expressing were injected into nude mice, the increased expression of PDCD4 blocked tumorigenesis and prolonged overall survival. Our study indicates the need to develop drugs that can modulate the expression of PDCD4 and test their efficacy in clinical trials.
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http://dx.doi.org/10.3389/fcell.2020.593685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693433PMC
November 2020

SKP1 promotes YAP-mediated colorectal cancer stemness via suppressing RASSF1.

Cancer Cell Int 2020 Dec 3;20(1):579. Epub 2020 Dec 3.

Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No. 600 Yishan Road, Xuhui District, Shanghai, 200233, People's Republic of China.

Background: Cancer stem cells (CSCs) have been recognized as an important drug target, however, the underlying mechanisms have not been fully understood. SKP1 is a traditional drug target for cancer therapy, while, whether SKP1 promotes colorectal cancer (CRC) stem cells (CRC-SCs) and the underlying mechanisms have remained elusive.

Methods: Human CRC cell lines and primary human CRC cells were used in this study. Gene manipulation was performed by lentivirus system. The mRNA and protein levels of target genes were examined by qRT-PCR and western blot. The sphere-forming and in vitro migration capacities were determined by sphere formation and transwell assay. The self-renewal was determined by limiting dilution assay. The tumorigenicity and metastasis of cancer cells were examined by xenograft model. The promoter activity was examined by luciferase reporter assay. Nuclear run-on and Chromatin immunoprecipitation-PCR (ChIP-PCR) assay were employed to examine the transcription and protein-DNA interaction. Co-immunoprecipitation assay was used to test protein-protein interaction. The relationship between gene expression and survival was analyzed by Kaplan-meier analysis. The correlation between two genes was analyzed by Spearman analysis. Data are represented as mean ± SD and the significance was determined by Student's t test.

Results: SKP1 was upregulated in CRC-SCs and predicted poor prognosis of colon cancer patients. Overexpression of SKP1 promoted the stemness of CRC cells reflected by increased sphere-forming, migration and self-renewal capacities as well as the expression of CSCs markers. In contrast, SKP1 depletion produced the opposite effects. SKP1 strengthened YAP activity and knockdown of YAP abolished the effect of SKP1 on the stemness of CRC cells. SKP1 suppressed RASSF1 at both mRNA and protein level. Overexpression of RASSF1 abolished the effect of SKP1 on YAP activity and CRC stemness.

Conclusion: Our results demonstrated that SKP1 suppresses RASSF1 at both mRNA and protein level, attenuates Hippo signaling, activates YAP, and thereby promoting the stemness of CRC cells.
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http://dx.doi.org/10.1186/s12935-020-01683-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7713163PMC
December 2020

A Two-Stage Fall Recognition Algorithm Based on Human Posture Features.

Sensors (Basel) 2020 Dec 5;20(23). Epub 2020 Dec 5.

School of Traffic & Transportation Engineering, Central South University, Changsha 410000, China.

Falls are seriously threatening the health of elderly. In order to reduce the potential danger caused by falls, this paper proposes a two-stage fall recognition algorithm based on human posture features. For preprocessing, we construct the new key features: deflection angles and spine ratio to describe the changes of human posture based on the human skeleton extracted by OpenPose. In the first stage, based on the variables: tendency symbol and steady symbol integrated by the scattered key features, we divide the human body state into three states: stable state, fluctuating state, and disordered state. By analyzing whether the body is in a stable state, the ADL (activities of daily living) actions with high stability can be preliminarily excluded. In the second stage: to further identify the confusing ADL actions and the fall actions, we innovatively design a time-continuous recognition algorithm. When human body is constantly in an unstable state, the human posture features: compare value γ, energy value ε, state score τ are proposed to form a feature vector, and support vector machine (SVM), K nearest neighbors (KNN), decision tree (DT), random forest (RF) are utilized for classification. Experiment results demonstrate that SVM with linear kernel function can distinguish falling actions best and our approach achieved a detection accuracy of 97.34%, precision of 98.50%, and the recall, F1 score are 97.33%, 97.91% respectively. Compared with previous state-of-art algorithms, our algorithm can achieve the highest recognition accuracy. It proves that our fall detection method is effective.
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http://dx.doi.org/10.3390/s20236966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7729773PMC
December 2020

LncRNA TMPO-AS1 Promotes Proliferation and Invasion by Sponging miR-383-5p in Glioma Cells.

Cancer Manag Res 2020 23;12:12001-12009. Epub 2020 Nov 23.

Department of Neurosurgery, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266000, People's Republic of China.

Purpose: Glioma is one of the most common malignant tumors affecting human health. Long non-coding RNA (lncRNA) TMPO-AS1 participates in the pathogenesis of various cancers. However, the role of lncRNA TMPO-AS1 in glioma remains largely unknown. This study aims to uncover the role of TMPO-AS1 and explore its potential mechanism in glioma.

Methods: Expression levels of TMPO-AS1 and miR-383-5p in glioma cell lines were measured by real-time quantitative PCR (RT-qPCR). CCK-8, colony formation, wound-healing, and Transwell assays were conducted to determine cell proliferation, migration and invasion abilities, respectively. Western blotting was applied to detect the expression of corresponding proteins. Immunofluorescence assay was performed to measure the expression of Ki67. The binding condition between TMPO-AS1 and miR-383-5p was verified by dual-luciferase reporter assay.

Results: We found that TMPO-AS1 was up-regulated while miR-383-5p was down-regulated in glioma cell lines, and knockdown of TMPO-AS1 significantly suppressed glioma cell proliferation, migration and invasion abilities. miR-383-5p was demonstrated to be a direct target of TMPO-AS1. Besides, inhibition of miR-383-5p abolished the effects of TMPO-AS1 knockdown on glioma cells.

Conclusion: In summary, our study revealed that inhibition of lncRNA TMPO-AS1 could suppress glioma progression through targeting miR-383-5p. TMPO-AS1 might be used as a therapeutic target for glioma treatment.
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http://dx.doi.org/10.2147/CMAR.S282539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7696628PMC
November 2020

Traffic-related organic and inorganic air pollution and risk of development of childhood asthma: A meta-analysis.

Environ Res 2021 03 18;194:110493. Epub 2020 Nov 18.

Tianjin Key Laboratory of Urban Transport Emission Research, State Environmental Protection Key Laboratory of Urban Ambient Air Particulate Matter Pollution Prevention and Control, College of Environmental Science and Engineering, Nankai University, Tianjin, 300350, PR China. Electronic address:

The effect of early childhood exposure to traffic-related air pollution (TRAP) on the development of asthma remains unclear. The aim of this study was to clarify potential associations between TRAP (fine particulate matter, PM; nitrogen dioxide, NO; Benzene and total volatile organic pollutants, TVOCs) and childhood asthma by integrating the results from previous studies. Elsevier, LISTA (EBSCO) and Web of Science databases were searched for relevant studies. Adjusted odds ratio (OR) with corresponding 95% confidence interval (CI) for the association between traffic-related air pollutants and health effects were recovered from individual studies and summary effect estimates (meta-OR) were generated in Review Manager 5.3. Twenty-seven studies were included in the meta-analysis and the results showed that TRAP increased the risk of asthma among children: PM (meta-OR = 1.07, 95% CI:1.00-1.13), NO (meta-OR = 1.11, 95% CI:1.06-1.17), Benzene (meta-OR: 1.21, 95% CI:1.13-1.29) and TVOC (meta-OR:1.06, 95% CI: 1.03-1.10). Sensitivity analyses supported these findings. In addition, regional analysis showed that ORs of inorganic TRAP (PM and NO) on the risk of childhood asthma were significantly higher in Asia than those in Europe and North America. Subsequent research should focus on the association between organic pollutants in TRAP and childhood asthma. Furthermore, the disentanglement between TRAP and other pollutant sources may be investigated in future studies.
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http://dx.doi.org/10.1016/j.envres.2020.110493DOI Listing
March 2021

Optically Controllable 2D Material/Complex Oxide Heterointerface.

Adv Sci (Weinh) 2020 Nov 20;7(21):2002393. Epub 2020 Aug 20.

Department of Chemistry National University of Singapore 3 Science Drive 3 Singapore 117543 Singapore.

Heterostructures play a vital role in functional devices on the basis of the individual constituents. Non-conventional heterostructures formed by stacking 2D materials onto structurally distinct materials are of great interest in achieving novel phenomena that are both scientifically and technologically relevant. Here, a heterostructure based on a 2D (molybdenum ditelluride) MoTe and an amorphous strontium titanium oxide (a-STO) thin film is reported. The heterostructure functions as a high-performance photodetector, which exhibits anomalous negative photoresponse in the pristine device due to the scattering effect from the light-induced O ions. The photoresponsivity and the specific detectivity are found to be >10 AW and >10 Jones, respectively, which are significantly higher than those in standard MoTe devices. Moreover, through tuning the light programming time, the photodetection behavior of the MoTe/a-STO heterostructure experiences a dynamic evolution from negative to positive. This is due to the optically controllable modulation of the interfacial states, which is further confirmed by the X-ray photoelectron spectroscopy and photoluminescence measurements. It is envisioned that the 2D material/a-STO heterostructure could be a potential platform for exploring new functional devices.
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http://dx.doi.org/10.1002/advs.202002393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7610330PMC
November 2020

Socioeconomic disparity in the association between long-term exposure to PM and mortality in 2640 Chinese counties.

Environ Int 2021 01 5;146:106241. Epub 2020 Nov 5.

Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. Electronic address:

Background: Although the association between long-term exposure to PM and mortality has been evaluated intensively, little is known about the socioeconomic disparity in the association.

Methods: We collected data on annual all-cause mortality, PM concentration, socioeconomic and demographic characteristics of 2640 counties from the two most recent Chinese censuses in 2000 and 2010. We applied the difference-in-differences (DID) method to estimate PM-mortality association for counties at different quartiles of literacy rate, college rate, urbanization rate and GDP per capita, respectively.

Results: Overall, every 10 µg/m increase in annual average PM was associated with 3.8% (95% confidence interval [CI]: 3.0-5.0) increase of all-cause mortality. The stratified analysis suggested higher health impact of exposure in counties with lower socioeconomic status. For counties of the lowest quartile (Q) of literacy rate, college rate, urbanization rate and GDP per capita, the effect estimates were 6.0% (95% CI: 4.2-7.7), 4.4% (95% CI: 2.8-6.0), 3.5% (95% CI: 2.0-5.1) and 4.9% (95% CI: 2.7-7.1), respectively. There was strong evidence for elevated risk in mortality associated with PM of all socioeconomic factors in the lowest quartile (Q) compared with the highest quartile counties (Q) (p-value for difference < 0.05).

Conclusions: There was socioeconomic disparity in the PM-mortality association in China. Dwellers living in less developed counties are more vulnerable to long-term exposure to ambient PM than those living in developed counties.
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http://dx.doi.org/10.1016/j.envint.2020.106241DOI Listing
January 2021

Improving smallholder farmers' maize yields and economic benefits under sustainable crop intensification in the North China Plain.

Sci Total Environ 2021 Apr 20;763:143035. Epub 2020 Oct 20.

State Key Laboratory of Crop Biology and College of Agronomy, Shandong Agricultural University, Tai'an 271018, Shandong, China.

To meet the food demands of a growing population, the maize production systems deployed by smallholders in China have tended towards extremely intensive planting and excessive use of fertilizers, which have caused serious environmental impacts. This study investigated the balance between the maize yield and nitrogen (N) input in the North China Plain (NCP), which is one of the most important grain-producing region in China. Our study compared yield simulations generated by the DSSAT-CERES-Maize model with actual data from a number of multi-site field experiments and an extensive household surveys encompassing 1671 farmers. The smallholders' maize cultivars, plant population, and amount of N input on the crop yield and how these affects the economic benefits were analyzed. The results showed that the average traditional farming methods' yield was 72% of the attainable yield, which means that farmers have ample room to improve their yields. We also found that the maize yields varied widely between farmers, and that most of them applied excessive amounts of N but failing to achieve an optimal yield due to poor fertilization management techniques. The study found that the economic benefits achieved by the farmers were low, but after deploying high-yield (HY) methods, the yield was increased by 34.9% and the economic benefits by 14.4%. The greenhouse gas (GHG) emissions associated with the traditional farming methods were high and could potentially be reduced by 48.6%. All in all, farmers should be given guidance on how to appropriately increase the plant population, reduce the input of N fertilizer, and optimize farmland management measures, so that China can achieve intensive but sustainable agricultural production at a lower environmental cost. It was concluded that there are still numerous biological and abiotic factors that restrict production increases by smallholders. These factors vary from region to region and require further investigation.
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http://dx.doi.org/10.1016/j.scitotenv.2020.143035DOI Listing
April 2021

Phase Diagram and Superconducting Dome of Infinite-Layer Nd_{1-x}Sr_{x}NiO_{2} Thin Films.

Phys Rev Lett 2020 Oct;125(14):147003

Department of Physics, Faculty of Science, National University of Singapore, Singapore 117551, Singapore.

Infinite-layer Nd_{1-x}Sr_{x}NiO_{2} thin films with Sr doping level x from 0.08 to 0.3 are synthesized and investigated. We find a superconducting dome x between 0.12 and 0.235 accompanied by a weakly insulating behavior in both under- and overdoped regimes. The dome is akin to that in the electron-doped 214-type and infinite-layer cuprate superconductors. For x≥0.18, the normal state Hall coefficient (R_{H}) changes the sign from negative to positive as the temperature decreases. The temperature of the sign changes decreases monotonically with decreasing x from the overdoped side and approaches the superconducting dome at the midpoint, suggesting a reconstruction of the Fermi surface with the dopant concentration across the dome.
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http://dx.doi.org/10.1103/PhysRevLett.125.147003DOI Listing
October 2020

Lung Expression of Human Angiotensin-Converting Enzyme 2 Sensitizes the Mouse to SARS-CoV-2 Infection.

Am J Respir Cell Mol Biol 2021 01;64(1):79-88

Tulane National Primate Research Center, Covington, Louisiana; and.

Preclinical mouse models that recapitulate some characteristics of coronavirus disease (COVID-19) will facilitate focused study of pathogenesis and virus-host responses. Human agniotensin-converting enzyme 2 (hACE2) serves as an entry receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to infect people via binding to envelope spike proteins. Herein we report development and characterization of a rapidly deployable COVID-19 mouse model. C57BL/6J (B6) mice expressing hACE2 in the lung were transduced by oropharyngeal delivery of the recombinant human adenovirus type 5 that expresses hACE2 (Ad5-hACE2). Mice were infected with SARS-CoV-2 at Day 4 after transduction and developed interstitial pneumonia associated with perivascular inflammation, accompanied by significantly higher viral load in lungs at Days 3, 6, and 12 after infection compared with Ad5-empty control group. SARS-CoV-2 was detected in pneumocytes in alveolar septa. Transcriptomic analysis of lungs demonstrated that the infected Ad5-hACE mice had a significant increase in IFN-dependent chemokines and , and genes associated with effector T-cell populations including C. Pathway analysis showed that several Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched in the data set, including cytokine-cytokine receptor interaction, the chemokine signaling pathway, the NOD-like receptor signaling pathway, the measles pathway, and the IL-17 signaling pathway. This response is correlative to clinical response in lungs of patients with COVID-19. These results demonstrate that expression of hACE2 via adenovirus delivery system sensitized the mouse to SARS-CoV-2 infection and resulted in the development of a mild COVID-19 phenotype, highlighting the immune and inflammatory host responses to SARS-CoV-2 infection. This rapidly deployable COVID-19 mouse model is useful for preclinical and pathogenesis studies of COVID-19.
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http://dx.doi.org/10.1165/rcmb.2020-0354OCDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7781002PMC
January 2021

A novel noble-metal-free MoC-InS heterojunction photocatalyst with efficient charge separation for enhanced photocatalytic H evolution under visible light.

J Colloid Interface Sci 2021 Jan 28;582(Pt B):488-495. Epub 2020 Aug 28.

Beijing Key Laboratory for Science and Application of Functional Molecular and Crystalline Materials, University of Science and Technology Beijing, Beijing 100083, China.

Currently, designing novel noble-metal-free photocatalysts with efficient carriers migration and catalytically active sites have been a researching hotspot in photocatalytic hydrogen evolution. In this paper, a novel noble-metal-free MoC-InS heterojunction was synthesized by a simple hydrothermal method. Morphology characterization revealed InS was attached to MoC. Electrochemical results showed MoC improved the interface conductivity, and promoted the transportation of photogenerated carriers. Under visible light, the optimal MoC-InS composite achieved a H generation rate of 535.58 μmol h g, which was 175.6 and 25.8 times higher than pristine InS (3.05 μmol h g) and InS-1% Pt (20.73 μmol h g). In addition, a reasonable mechanism of the elevated photocatalytic activity was also discussed. This study demonstrates commercial MoC has an important effect of separating carriers and replacing Pt as co-catalyst in heterojunctions. This research also provides a method to design and synthesize new noble-metal-free photocatalysts for excellent hydrogen production activity.
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http://dx.doi.org/10.1016/j.jcis.2020.08.083DOI Listing
January 2021

A Brain-Inspired Adaptive Space Representation Model Based on Grid Cells and Place Cells.

Comput Intell Neurosci 2020 11;2020:1492429. Epub 2020 Aug 11.

Information and Navigation College, Air Force Engineering University, Xi'an, Shaanxi 710077, China.

Grid cells and place cells are important neurons in the animal brain. The information transmission between them provides the basis for the spatial representation and navigation of animals and also provides reference for the research on the autonomous navigation mechanism of intelligent agents. Grid cells are important information source of place cells. The supervised learning and unsupervised learning models can be used to simulate the generation of place cells from grid cell inputs. However, the existing models preset the firing characteristics of grid cell. In this paper, we propose a united generation model of grid cells and place cells. First, the visual place cells with nonuniform distribution generate the visual grid cells with regional firing field through feedforward network. Second, the visual grid cells and the self-motion information generate the united grid cells whose firing fields extend to the whole space through genetic algorithm. Finally, the visual place cells and the united grid cells generate the united place cells with uniform distribution through supervised fuzzy adaptive resonance theory (ART) network. Simulation results show that this model has stronger environmental adaptability and can provide reference for the research on spatial representation model and brain-inspired navigation mechanism of intelligent agents under the condition of nonuniform environmental information.
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http://dx.doi.org/10.1155/2020/1492429DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439180PMC
July 2021

Target Area Extraction Algorithm for the In Vivo Fluorescence Imaging of Small Animals.

ACS Omega 2020 Aug 3;5(32):20100-20106. Epub 2020 Aug 3.

CAS Key Laboratory of Bio-Medical Diagnostics, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, P. R. China.

Bio-optical imaging can noninvasively describe specific biochemical reaction events in small animals using endogenous or exogenous imaging reagents to label cells, proteins, or DNA. The fluorescence optical bio-imaging system excites the fluorescent group to a high energy state by excitation light and then generates emission light. However, many substances in the organism will also emit fluorescence after being excited by the excitation light, and the nonspecific fluorescence generated will affect the detection sensitivity. This paper designs and develops a set of high-level biosafety in vivo fluorescence imaging system for small animals suitable for virology research and proposes a target area extraction algorithm for fluorescence images. The fluorescence image target extraction algorithm first maps the nonlinear separation data in the low-dimensional space to the high-dimensional space. Then, based on the analysis of the characteristics of the fluorescent region, a method for discriminating the target fluorescent region based on the two-step entropy function is proposed, and the real target fluorescent region is obtained according to the set connected region. Based on the experiment of collecting and analyzing the in vivo fluorescent images of mice, it is verified that the proposed algorithm can automatically extract the target fluorescent region better than the classical linear model. It shows that the proposed algorithm is less affected by background fluorescence, and the estimated separated spectrum based on this method is closer to the real target spectrum.
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http://dx.doi.org/10.1021/acsomega.0c01733DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439258PMC
August 2020

Room-Temperature Colossal Magnetoresistance in Terraced Single-Layer Graphene.

Adv Mater 2020 Sep 2;32(37):e2002201. Epub 2020 Aug 2.

NUSNNI, National University of Singapore, Singapore, 117411, Singapore.

Disorder-induced magnetoresistance (MR) effect is quadratic at low perpendicular magnetic fields and linear at high fields. This effect is technologically appealing, especially in 2D materials such as graphene, since it offers potential applications in magnetic sensors with nanoscale spatial resolution. However, it is a great challenge to realize a graphene magnetic sensor based on this effect because of the difficulty in controlling the spatial distribution of disorder and enhancing the MR sensitivity in the single-layer regime. Here, a room-temperature colossal MR of up to 5000% at 9 T is reported in terraced single-layer graphene. By laminating single-layer graphene on a terraced substrate, such as TiO -terminated SrTiO , a universal one order of magnitude enhancement in the MR compared to conventional single-layer graphene devices is demonstrated. Strikingly, a colossal MR of >1000% is also achieved in the terraced graphene even at a high carrier density of ≈10 cm . Systematic studies of the MR of single-layer graphene on various oxide- and non-oxide-based terraced surfaces demonstrate that the terraced structure is the dominant factor driving the MR enhancement. The results open a new route for tailoring the physical property of 2D materials by engineering the strain through a terraced substrate.
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http://dx.doi.org/10.1002/adma.202002201DOI Listing
September 2020

Dioscin Protects against Aβ1-42 Oligomers-Induced Neurotoxicity via the Function of SIRT3 and Autophagy.

Chem Pharm Bull (Tokyo) 2020 ;68(8):717-725

Department of Geriatrics, Hwa Mei Hospital, University of Chinese Academy of Sciences, Ningbo Institute of Life and Health Industry, University of Chinese Academy of Sciences.

Alzheimer's disease (AD) is a common neurodegenerative disease with high incidence among old people. Dioscin is a product extracted from natural herbs, which has multiple pharmacological activities. In this study, we investigated the potential effects of disocin on amyloid-β peptide (Aβ1-42) oligomers-treated HT22 cells. Aβ1-42 oligomers induced great neurotoxicity to HT22 cells as examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The results of terminal deoxynucleoitidyl transferase-mediated deoxyuridine triphosphate biotin nich end labeling (TUNEL) staining and flow cytometry indicated that Aβ1-42 oligomers led to increased apoptosis and generation of reactive oxygen species (ROS) in HT22 cells. However, dioscin could remarkably inhibit the neurotoxicity induced by Aβ1-42 oligomers, as well as decrease the apoptosis and ROS generation. Sirtuin-3 (SIRT3) staining and quantification indicated that dioscin upregulated the expression of neuroprotective SIRT3. Moreover, dioscin induced the formation of autophagosomes and autolysosomes in HT22 cells. Dioscin also enhanced the levels of Beclin-1 and LC3-II while decreased the level of p62. These results suggested that dioscin could activate autophagy in HT22 cells. It was also found that knocking down SIRT3 resulted in the downregulation of Beclin-1, LC3-II and the aggregation of p62, suggesting that SIRT3 was an important regulator in autophagy. Furthermore, we found that knocking down SIRT3 or inhibiting autophagy suppressed the protective effects of dioscin on Aβ1-42 oligomers-induced neurotoxicity, apoptosis and ROS generation. These results revealed that SIRT3 and autophagy functioned together in the neuroprotective mechanisms of dioscin. Therefore, dioscin might be a promising drug to protect against Aβ1-42 oligomers-induced neurotoxicity and reduce neuron damage or death in AD.
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http://dx.doi.org/10.1248/cpb.c20-00046DOI Listing
February 2021

Long Non-coding RNA MRUL Contributes to Osteosarcoma Progression Through the miR-125a-5p/FUT4 Axis.

Front Genet 2020 25;11:672. Epub 2020 Jun 25.

Department of Medical Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.

Osteosarcoma (OS) originates in the skeletal system and has a rising global incidence. Long Non-coding RNAs (lncRNAs) are key regulators of human cancers development and progression. However, their roles in the development of OS are not well understood. This research aimed to investigate the effect of a long non-coding RNA (lncRNA), MRUL, on OS and revealed its potential molecular mechanisms. The bioinformatics analysis demonstrated that lncRNA MRUL was involved in regulating nucleic acid-templated transcription, cellular macromolecule biosynthetic process, immune response, and inflammatory response. In this work, the expression of lncRNA MRUL was detected by quantitative real-time polymerase chain reaction (qRT-RCR) in both cancer tissues and cell lines. We found that lncRNA MRUL was up-regulated in cancer tissues and cell lines. Functional experiments showed that knockdown of lncRNA MRUL inhibited OS cell proliferation, and metastasis. At the same time, we found that lncRNA MRUL interacted with miR-125a-5p to suppress FUT4 expression. Moreover, inhibition of miR-125a-5p abrogated the biological roles of lncRNA MRUL knockdown on OS cell proliferation, migration, and invasion. In conclusion, these results demonstrated that OS-upregulated lncRNA MRUL promoted cell proliferation, and metastasis via negatively regulating miR-125a-5p, and imply that lncRNA MRUL may be a potential biomarker for OS.
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http://dx.doi.org/10.3389/fgene.2020.00672DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330113PMC
June 2020
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