Publications by authors named "Jingyi Yang"

126 Publications

Conductive polyethersulfone membrane facilely prepared by simultaneous phase inversion method for enhanced anti-fouling and separation under low driven-pressure.

J Environ Manage 2021 Jul 24;297:113363. Epub 2021 Jul 24.

Shenzhen Key Laboratory of Water Resource Utilization and Environmental Pollution Control, Harbin Institute of Technology, Shenzhen, Guangdong Province, 518055, China. Electronic address:

Electrically conductive membranes have been regarded as a new alternative to overcome the crucial drawbacks of membranes, including permeability-selectivity trade-off and fouling. It is still challenging to prepare conductive membranes with good mechanical strength, high conductivity and stable separation performance by reliable materials and methods. This work developed a facile method of simultaneous phase inversion to prepare electrically conductive polyethersulfone (PES) membranes with carboxylic multiwalled carbon nanotubes (MWCNT) and graphene (Gr). The resultant MWCNT/Gr/PES nanocomposite membranes are composed of the upper MWCNT/Gr layer with good conductivity and the base PES layer providing mechanical support. MWCNT as nanofillers effectively turns the insulting PES layers to be electrically conductive. With the dispersing and bridging functions of Gr, the MWCNT/Gr layer shows an enhanced electric conductivity of 0.10 S/cm. This MWCNT/Gr/PES membrane in an electro-filtration cell achieves excellent retention of Cu(II) ions up to 98 % and a high flux of 94.5 L m∙h∙bar under a low driven-pressure of 0.1 MPa. The conductive membrane also shows improved anti-fouling capability during protein filtration, due mainly to the electrostatic repulsion and hydrogen evolution reaction on the electrode. This facile strategy has excellent potential in electro-assistant membrane filtration for fouling control and effective separation.
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http://dx.doi.org/10.1016/j.jenvman.2021.113363DOI Listing
July 2021

A safe and effective mucosal RSV vaccine in mice consisting of RSV phosphoprotein and flagellin variant.

Cell Rep 2021 Jul;36(3):109401

Vaccine and Immunology Research Center, Translational Medical Research Institute, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China; Mucosal Immunity Research Group, State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China. Electronic address:

Respiratory syncytial virus (RSV) is a major cause of serious acute lower respiratory tract infection in infants and the elderly. The lack of a licensed RSV vaccine calls for the development of vaccines with other targets and vaccination strategies. Here, we construct a recombinant protein, designated P-KFD1, comprising RSV phosphoprotein (P) and the E.-coli-K12-strain-derived flagellin variant KFD1. Intranasal immunization with P-KFD1 inhibits RSV replication in the upper and lower respiratory tract and protects mice against lung disease without vaccine-enhanced disease (VED). The P-specific CD4 T cells provoked by P-KFD1 intranasal (i.n.) immunization either reside in or migrate to the respiratory tract and mediate protection against RSV infection. Single-cell RNA sequencing (scRNA-seq) and carboxyfluorescein succinimidyl ester (CFSE)-labeled cell transfer further characterize the Th1 and Th17 responses induced by P-KFD1. Finally, we find that anti-viral protection depends on either interferon-γ (IFN-γ) or interleukin-17A (IL-17A). Collectively, P-KFD1 is a promising safe and effective mucosal vaccine candidate for the prevention of RSV infection.
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http://dx.doi.org/10.1016/j.celrep.2021.109401DOI Listing
July 2021

The complete chloroplast genome sequence of C. H. Wright.

Mitochondrial DNA B Resour 2021 6;6(8):2235-2236. Epub 2021 Jul 6.

College of Forestry, Guizhou University, Guiyang, China.

C. H. Wright is a climbing shrub that can be used for herbal medicine. The complete chloroplast genome sequence of was determined in this study. It is 158,246 bp in length with a GC content of 37.12%, and consists of a pair of inverted repeat (IR) regions of 27,175 bp, a large single copy (LSC) region of 85,229 bp, and a small single copy (SSC) region of 18,667 bp. The genome encoded 132 genes, including 86 protein-coding genes, 38 tRNA genes, and 8 rRNA genes. The phylogenetic analysis showed that is phylogenetically closely related to and .
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http://dx.doi.org/10.1080/23802359.2021.1947914DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266230PMC
July 2021

Structure-Based Discovery of Novel Nonpeptide Inhibitors Targeting SARS-CoV-2 M.

J Chem Inf Model 2021 Jul 19. Epub 2021 Jul 19.

School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, China.

The continual spread of novel coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), posing a severe threat to the health worldwide. The main protease (M, alias 3CL) of SARS-CoV-2 is a crucial enzyme for the maturation of viral particles and is a very attractive target for designing drugs to treat COVID-19. Here, we propose a multiple conformation-based virtual screening strategy to discover inhibitors that can target SARS-CoV-2 M. Based on this strategy, nine M structures and a protein mimetics library with 8960 commercially available compounds were prepared to carry out ensemble docking for the first time. Five of the nine structures are apo forms presented in different conformations, whereas the other four structures are holo forms complexed with different ligands. The surface plasmon resonance assay revealed that 6 out of 49 compounds had the ability to bind to SARS-CoV-2 M. The fluorescence resonance energy transfer experiment showed that the biochemical half-maximal inhibitory concentration (IC) values of the six compounds could hamper M activities ranged from 0.69 ± 0.05 to 2.05 ± 0.92 μM. Evaluation of antiviral activity using the cell-based assay indicated that two compounds (Z1244904919 and Z1759961356) could strongly inhibit the cytopathic effect and reduce replication of the living virus in Vero E6 cells with the half-maximal effective concentrations (EC) of 4.98 ± 1.83 and 8.52 ± 0.92 μM, respectively. The mechanism of the action for the two inhibitors were further elucidated at the molecular level by molecular dynamics simulation and subsequent binding free energy analysis. As a result, the discovered noncovalent reversible inhibitors with novel scaffolds are promising antiviral drug candidates, which may be used to develop the treatment of COVID-19.
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http://dx.doi.org/10.1021/acs.jcim.1c00355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8315252PMC
July 2021

Comparative Microbial Profiles of Caries and Black Extrinsic Tooth Stain in Primary Dentition.

Caries Res 2021 Jul 9:1-12. Epub 2021 Jul 9.

Department of Paediatric Dentistry, Peking University School and Hospital of Stomatology & National Clinical Research Center for Oral Diseases & National Engineering Laboratory for Digital and Material Technology of Stomatology & Beijing Key Laboratory of Digital Stomatology, Beijing, China.

Extrinsic black tooth stain (BS) is a common oral disease associated with lower caries experience in preschool children, although the microbiotic features contributing to the low risk of caries in this group remain elusive. In this study, we aimed at identifying the dominant bacteria in dental plaque to indicate the incidence of caries in the primary dentition. Subjects were divided into 3 groups based on the clinical examination: group CF, children without pigment who had no caries lesions or restorations (n = 18); group CS, children who were diagnosed with severe early childhood caries (n = 17); and group BS, children with pigment (black extrinsic stain) without caries or restorations (n = 15). The total microbial genomic DNA was extracted and subjected to bacterial 16S ribosomal RNA gene sequencing using an Illumina HiSeq platform. The differential dominant bacteria were determined using Wilcoxon rank-sum testing and linear discriminant analysis effect size (LEfSe). Co-occurrence network analysis was performed using sparse correlations for compositional data, calculation and functional features were predicted using PICRUSt. Interestingly, our results showed that the relative abundance of Pseudopropionibacterium, Actinomyces, Rothia, and Cardiobacterium was from high to low and that of Porphyromonas was low to high in the BS, CF, and CS groups, consistent with the clinical incidence of caries in the 3 groups. Moreover, an increased level of Selenomonas_3, Fusobacterium, and Leptotrichia was associated with high caries prevalence. We found that the interactions among genera in the BS and CS plaque communities are less complex than those in the CF communities at the taxon level. Functional features, including cofactor and vitamin metabolism, glycan biosynthesis and metabolism, and translation, significantly increased in caries plaque samples. These bacterial competition- and commensalism-induced changes in microbiota would result in a change of their symbiotic function, finally affecting the balance of oral microflora.
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http://dx.doi.org/10.1159/000517006DOI Listing
July 2021

Recent Advances in Computer-aided Antiviral Drug Design Targeting HIV-1 Integrase and Reverse Transcriptase Associated Ribonuclease H.

Curr Med Chem 2021 Jul 7. Epub 2021 Jul 7.

School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, China.

Acquired immunodeficiency syndrome (AIDS) has been a chronic, life-threatening disease for a long time. However, a broad range of antiretroviral drug regimens are applicable for the successful suppression of virus replication in human immunodeficiency virus type 1 (HIV-1) infected people. The mutation-induced drug resistance problems during the treatment of AIDS forced people to continuously look for new antiviral agents. HIV-1 integrase (IN) and reverse transcriptase associated ribonuclease (RT-RNase H), two pivotal enzymes in HIV-1 replication progress, has gain popularity as drug-able targets for designing novel HIV-1 antiviral drugs. During the development of HIV-1 IN and/or RT-RNase H inhibitors, computer-aided drug design (CADD), including homology modeling, pharmacophore, docking, molecular dynamics (MD) simulation, and binding free energy calculation, represents a significant tool to accelerate the discovery of new drug candidates and reduce costs in antiviral drug development. In this review, we summarized the recent advances in the design of single-and dual-target inhibitors against HIV-1 IN or/and RT-RNase H as well as the prediction of mutation-induced drug resistance based on computational methods. We highlighted the results of the reported literature and proposed some perspectives on the design of novel and more effective antiviral drugs in the future.
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http://dx.doi.org/10.2174/0929867328666210708090123DOI Listing
July 2021

Integrated Genomic Analyses of Cutaneous T Cell Lymphomas Reveal the Molecular Bases for Disease Heterogeneity.

Blood 2021 Jun 11. Epub 2021 Jun 11.

Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States.

Cutaneous T cell lymphomas (CTCLs) are a clinically heterogeneous collection of lymphomas of the skin-homing T cell. To identify molecular drivers of disease phenotypes, we assembled a cohort of CTCLs with representative samples from diverse disease subtypes and stages. Via DNA/RNA-sequencing, immunophenotyping, and ex vivo functional assays, we identified the landscape of putative driver genes, elucidated genetic relationships between CTCLs across disease stages, and inferred molecular subtypes in patients with stage-matched leukemic disease. Collectively, our analysis identified 86 putative driver genes, including 19 genes not previously implicated in this disease. 2 mutations have never been previously described for any cancer. Functionally, multiple mutations augment T cell receptor-dependent proliferation, highlighting the importance of this pathway in lymphomagenesis. To identify putative genetic causes of disease heterogeneity, we examined the distribution of driver genes across clinical cohorts. There are broad similarities across disease stages. Many driver genes are shared by mycosis fungoides (MF) and Sezary syndrome (SS). However, there are significantly more structural variants in leukemic disease, leading to highly recurrent deletions of putative tumor suppressors that are uncommon in early-stage skin-centered MF. For example, TP53 is deleted in 7% and 87% of MF and SS, respectively. In both human and mouse samples, PD1 mutations drive aggressive behavior. PD1 wild-type lymphomas show features of T cell exhaustion. PD1 deletions are sufficient to reverse the exhaustion phenotype, promote a FOXM1-driven transcriptional signature, and predict significantly worse survival. Collectively, our findings clarify CTCL genetics and provide novel insights into pathways driving diverse disease phenotypes.
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http://dx.doi.org/10.1182/blood.2020009655DOI Listing
June 2021

Accurate Tumor Segmentation via Octave Convolution Neural Network.

Front Med (Lausanne) 2021 19;8:653913. Epub 2021 May 19.

The State Key Laboratory of Precision Measurement Technology and Instruments, Department of Precision Instrument, Tsinghua University, Beijing, China.

Three-dimensional (3D) liver tumor segmentation from Computed Tomography (CT) images is a prerequisite for computer-aided diagnosis, treatment planning, and monitoring of liver cancer. Despite many years of research, 3D liver tumor segmentation remains a challenging task. In this paper, we propose an effective and efficient method for tumor segmentation in liver CT images using encoder-decoder based octave convolution networks. Compared with other convolution networks utilizing standard convolution for feature extraction, the proposed method utilizes octave convolutions for learning multiple-spatial-frequency features, thus can better capture tumors with varying sizes and shapes. The proposed network takes advantage of a fully convolutional architecture which performs efficient end-to-end learning and inference. More importantly, we introduce a deep supervision mechanism during the learning process to combat potential optimization difficulties, and thus the model can acquire a much faster convergence rate and more powerful discrimination capability. Finally, we integrate octave convolutions into the encoder-decoder architecture of UNet, which can generate high resolution tumor segmentation in one single forward feeding without post-processing steps. Both architectures are trained on a subset of the LiTS (Liver Tumor Segmentation) Challenge. The proposed approach is shown to significantly outperform other networks in terms of various accuracy measures and processing speed.
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http://dx.doi.org/10.3389/fmed.2021.653913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8169966PMC
May 2021

Highly selective and robust single-atom catalyst Ru/NC for reductive amination of aldehydes/ketones.

Nat Commun 2021 Jun 2;12(1):3295. Epub 2021 Jun 2.

CAS Key Laboratory of Science and Technology on Applied Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China.

Single-atom catalysts (SACs) have emerged as a frontier in heterogeneous catalysis due to the well-defined active site structure and the maximized metal atom utilization. Nevertheless, the robustness of SACs remains a critical concern for practical applications. Herein, we report a highly active, selective and robust Ru SAC which was synthesized by pyrolysis of ruthenium acetylacetonate and N/C precursors at 900 °C in N followed by treatment at 800 °C in NH. The resultant Ru-N structure exhibits moderate capability for hydrogen activation even in excess NH, which enables the effective modulation between transimination and hydrogenation activity in the reductive amination of aldehydes/ketones towards primary amines. As a consequence, it shows superior amine productivity, unrivalled resistance against CO and sulfur, and unexpectedly high stability under harsh hydrotreating conditions compared to most SACs and nanocatalysts. This SAC strategy will open an avenue towards the rational design of highly selective and robust catalysts for other demanding transformations.
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http://dx.doi.org/10.1038/s41467-021-23429-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8172939PMC
June 2021

Brain Tumor Segmentation via Multi-Modalities Interactive Feature Learning.

Front Med (Lausanne) 2021 13;8:653925. Epub 2021 May 13.

Department of Radiology, The 1st Medical Center, Chinese PLA General Hospital, Beijing, China.

Automatic segmentation of brain tumors from multi-modalities magnetic resonance image data has the potential to enable preoperative planning and intraoperative volume measurement. Recent advances in deep convolutional neural network technology have opened up an opportunity to achieve end-to-end segmenting the brain tumor areas. However, the medical image data used in brain tumor segmentation are relatively scarce and the appearance of brain tumors is varied, so that it is difficult to find a learnable pattern to directly describe tumor regions. In this paper, we propose a novel cross-modalities interactive feature learning framework to segment brain tumors from the multi-modalities data. The core idea is that the multi-modality MR data contain rich patterns of the normal brain regions, which can be easily captured and can be potentially used to detect the non-normal brain regions, i.e., brain tumor regions. The proposed multi-modalities interactive feature learning framework consists of two modules: cross-modality feature extracting module and attention guided feature fusing module, which aim at exploring the rich patterns cross multi-modalities and guiding the interacting and the fusing process for the rich features from different modalities. Comprehensive experiments are conducted on the BraTS 2018 benchmark, which show that the proposed cross-modality feature learning framework can effectively improve the brain tumor segmentation performance when compared with the baseline methods and state-of-the-art methods.
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http://dx.doi.org/10.3389/fmed.2021.653925DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158657PMC
May 2021

Rapid isolation and immune profiling of SARS-CoV-2 specific memory B cell in convalescent COVID-19 patients via LIBRA-seq.

Signal Transduct Target Ther 2021 05 17;6(1):195. Epub 2021 May 17.

School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen, China.

B cell response plays a critical role against SARS-CoV-2 infection. However, little is known about the diversity and frequency of the paired SARS-CoV-2 antigen-specific BCR repertoire after SARS-CoV-2 infection. Here, we performed single-cell RNA sequencing and VDJ sequencing using the memory and plasma B cells isolated from five convalescent COVID-19 patients, and analyzed the spectrum and transcriptional heterogeneity of antibody immune responses. Via linking BCR to antigen specificity through sequencing (LIBRA-seq), we identified a distinct activated memory B cell subgroup (CD11c CD95) had a higher proportion of SARS-CoV-2 antigen-labeled cells compared with memory B cells. Our results revealed the diversity of paired BCR repertoire and the non-stochastic pairing of SARS-CoV-2 antigen-specific immunoglobulin heavy and light chains after SARS-CoV-2 infection. The public antibody clonotypes were shared by distinct convalescent individuals. Moreover, several antibodies isolated by LIBRA-seq showed high binding affinity against SARS-CoV-2 receptor-binding domain (RBD) or nucleoprotein (NP) via ELISA assay. Two RBD-reactive antibodies C14646P3S and C2767P3S isolated by LIBRA-seq exhibited high neutralizing activities against both pseudotyped and authentic SARS-CoV-2 viruses in vitro. Our study provides fundamental insights into B cell response following SARS-CoV-2 infection at the single-cell level.
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http://dx.doi.org/10.1038/s41392-021-00610-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8127497PMC
May 2021

Understanding the Polypharmacological Profiles of Triple Reuptake Inhibitors by Molecular Simulation.

ACS Chem Neurosci 2021 06 12;12(11):2013-2026. Epub 2021 May 12.

School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, China.

The triple reuptake inhibitors (TRIs) class is a class of effective inhibitors of human monoamine transporters (hMATs), which includes dopamine, norepinephrine, and serotonin transporters (hDATs, hNETs, and hSERTs). Due to the high degree of structural homology of the binding sites of those transporters, it is a great challenge to design potent TRIs with fine-tuned binding profiles. The molecular determinants responsible for the binding selectivity of TRIs to hDATs, hNETs, and hSERTs remain elusive. In this study, the solved X-ray crystallographic structure of hSERT in complex with escitalopram was used as a basis for modeling nine complexes of three representative TRIs (SEP225289, NS2359, and EB1020) bound to their corresponding targets. Molecular dynamics (MD) and effective post-trajectory analysis were performed to estimate the drug binding free energies and characterize the selective profiles of each TRI to hMATs. The common binding mode of studied TRIs to hMATs was revealed by hierarchical clustering analysis of the per-residue energy. Furthermore, the combined protein-ligand interaction fingerprint and residue energy contribution analysis indicated that several conserved and nonconserved "Warm Spots" such as S149, V328, and M427 in hDAT, F317, F323, and V325 in hNET and F335, F341, and V343 in hSERT were responsible for the TRI-binding selectivity. These findings provided important information for rational design of a single drug with better polypharmacological profiles through modulating multiple targets.
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http://dx.doi.org/10.1021/acschemneuro.1c00127DOI Listing
June 2021

Surface-enhanced Raman spectroscopic chemical imaging reveals distribution of pectin and its co-localization with xyloglucan inside onion epidermal cell wall.

PLoS One 2021 5;16(5):e0250650. Epub 2021 May 5.

Department of Agricultural and Biosystems Engineering, Iowa State University, Ames, IA, United States of America.

The primary plant cell wall is a complex matrix composed of interconnected polysaccharides including cellulose, hemicellulose, and pectin. Changes of this dynamic polysaccharide system play a critical role during plant cell development and differentiation. A better understanding of cell wall architectures can provide insight into the plant cell development. In this study, a Raman spectroscopic imaging approach was developed to visualize the distribution of plant cell wall polysaccharides. In this approach, Surface-enhanced Raman scattering (SERS through self-assembled silver nanoparticles) was combined with Raman labels (4-Aminothiophenol. 4ATP) and targeted enzymatic hydrolysis to improve the sensitivity, specificity, and throughput of the Raman imaging technique, and to reveal the distribution of pectin and its co-localization with xyloglucan inside onion epidermal cell (OEC) wall. This technique significantly decreased the required spectral acquisition time. The resulted Raman spectra showed a high Raman signal. The resulted Raman images successfully revealed and characterized the pectin distribution and its co-localization pattern with xyloglucan in OEC wall.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0250650PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099099PMC
May 2021

Mucosal epithelial cells: the initial sentinels and responders controlling and regulating immune responses to viral infections.

Cell Mol Immunol 2021 Jul 29;18(7):1628-1630. Epub 2021 Apr 29.

Vaccine and Immunology Research Center, Translational Medical Research Institute, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.

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http://dx.doi.org/10.1038/s41423-021-00650-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8082051PMC
July 2021

Computational design and modeling of nanobodies toward SARS-CoV-2 receptor binding domain.

Chem Biol Drug Des 2021 07 13;98(1):1-18. Epub 2021 May 13.

School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing, China.

The ongoing pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global health concern and pose a serious threat to humanity. There is an urgent need for developing therapeutic drugs and (or) biologics to prevent the spread of the virus. The life cycle of SARS-CoV-2 shows that the virus enters host cells by first binding to angiotensin-converting enzyme 2 (ACE2) through its spike protein receptor-binding domain (RBD). Therefore, blocking the binding between of ACE2 and SARS-CoV-2 RBD can inhibit the virus infection in the host cells. In this study, by grafting the complementarity-determining regions (CDRs) of developed SARS-CoV, MERS-CoVs specific neutralizing antibodies (nAbs) include monoclonal antibodies (mAbs) as well as SARS-CoV-2 mAbs onto a known stable nanobody (Nb) scaffold, and a total of 16 Nbs sequences were designed. Five Nbs, namely CS01, CS02, CS03, CS10, and CS16, were selected based on the free energy landscape of protein docking verified by the recently reported Nb-RBD cocrystal structures. CS01, CS02, and CS03 occupied the ACE2 binding site of RBD, while CS10 and CS16 were proposed to inhibit the interaction between RBD and ACE2 through an allosteric mechanism. Based on the structures of the five Nbs in complex with RBD, seven brand-new Nbs with enhanced binding affinities (CS02_RD01, CS03_RD01, CS03_RD02, CS03_RD03, CS03_RD04, CS16_RD01, and CS16_RD02) were generated by redesign of residues on the interface of the five Nbs contact with SARS-CoV-2 RBD. In addition, the identified "hot spots" on the interface of each complex provide useful information to understand the binding mechanism of designed Nbs to SARS-CoV-2 RBD. In sum, the predicted stabilities and high binding affinities of the 11 (re)designed Nbs indicating the potential of the developed computational framework in this work to design effective agents to block the infection of SARS-CoV-2.
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http://dx.doi.org/10.1111/cbdd.13847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250495PMC
July 2021

Highly active and stable Ir nanoclusters derived from Ir/MgAlO single-atom catalysts.

J Chem Phys 2021 Apr;154(13):131105

CAS Key Laboratory of Science and Technology on Applied Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Single-atom catalysts (SACs) prepared by the atom trapping method often possess high stability yet have limited advantages regarding catalytic performance due to the strong metal-support interaction. Using these SACs as seeds to develop supported nanoclusters or nanoparticles has, however, been proven to be effective in improving the catalysts' intrinsic activity. Herein, we have prepared extremely stable Ir SACs supported by MgAlO via atomic trapping and used them as seeds to fabricate highly active and stable Ir nanocluster catalysts by high-temperature reduction. The activity toward NO decomposition increased by more than ten times compared with that of the parent Ir SACs. This study provides a new avenue to design and develop highly active and stable catalysts for industrial use.
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http://dx.doi.org/10.1063/5.0048565DOI Listing
April 2021

Highly efficient Co single-atom catalyst for epoxidation of plant oils.

J Chem Phys 2021 Apr;154(13):131103

CAS Key Laboratory of Science and Technology on Applied Catalysis, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China.

Epoxidation of bio-derived plant oils is a sustainable route to manufacturing plasticizers, additives in lubricants, and other chemicals. The traditional synthetic approaches suffer from the employment of corrosive mineral acid or expensive peroxides (e.g., HO). In this work, we report the epoxidation of plant oils using O as the terminal oxidant catalyzed by Co-N-C/SiO single-atom catalyst. The single-atom dispersion of cobalt is confirmed by high-angle annular dark field-STEM and x-ray absorption fine structure techniques. In the epoxidation of methyl oleate under mild reaction conditions (35 °C, 0.1 MPa O), 99% selectivity to the desired product is achieved at full conversion. Even for crude oils, Co-N-C/SiO is also effective and good yields of the corresponding epoxides are obtained. In addition, the catalyst is easily recovered and can be reused five times without obvious decay in catalytic activity/selectivity. A superoxide radical involved reaction mechanism is proposed on the basis of kinetic study and EPR experiment.
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http://dx.doi.org/10.1063/5.0046166DOI Listing
April 2021

Broad phenotypic alterations and potential dysfunction of lymphocytes in individuals clinically recovered from COVID-19.

J Mol Cell Biol 2021 07;13(3):197-209

Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508, China.

Although millions of patients have clinically recovered from COVID-19, little is known about the immune status of lymphocytes in these individuals. In this study, the peripheral blood mononuclear cells of a clinically recovered (CR) cohort were comparatively analyzed with those of an age- and sex-matched healthy donor cohort. We found that CD8+ T cells in the CR cohort had higher numbers of effector T cells and effector memory T cells but lower Tc1 (IFN-γ+), Tc2 (IL-4+), and Tc17 (IL-17A+) cell frequencies. The CD4+ T cells of the CR cohort were decreased in frequency, especially the central memory T cell subset. Moreover, CD4+ T cells in the CR cohort showed lower programmed cell death protein 1 (PD-1) expression and had lower frequencies of Th1 (IFN-γ+), Th2 (IL-4+), Th17 (IL-17A+), and circulating follicular helper T (CXCR5+PD-1+) cells. Accordingly, the proportion of isotype-switched memory B cells (IgM-CD20hi) among B cells in the CR cohort showed a significantly lower proportion, although the level of the activation marker CD71 was elevated. For CD3-HLA-DR- lymphocytes in the CR cohort, in addition to lower levels of IFN-γ, granzyme B and T-bet, the correlation between T-bet and IFN-γ was not observed. Additionally, by taking into account the number of days after discharge, all the phenotypes associated with reduced function did not show a tendency toward recovery within 4‒11 weeks. The remarkable phenotypic alterations in lymphocytes in the CR cohort suggest that  severe acute respiratory syndrome coronavirus 2 infection profoundly affects lymphocytes and potentially results in dysfunction even after clinical recovery.
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http://dx.doi.org/10.1093/jmcb/mjab014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7989217PMC
July 2021

Characteristics of T-cell responses in COVID-19 patients with prolonged SARS-CoV-2 positivity - a cohort study.

Clin Transl Immunology 2021 4;10(3):e1259. Epub 2021 Mar 4.

Shanghai Public Health Clinical Center Fudan University Shanghai China.

Objective: SARS-CoV-2 has caused a worldwide pandemic of COVID-19. The existence of prolonged SARS-CoV-2 positivity (PP) has further increased the burden on the health system. Since T cells are vital for viral control, we aimed to evaluate the characteristics of T-cell responses associated with PP.

Methods: We established a PP cohort and two age- and sex-matched control cohorts: a regular clinical recovery (CR) cohort and a healthy donor (HD) cohort. The mean time for RNA negativity conversion in the PP cohort was markedly longer than that in the CR cohort (66.2 vs 25.3 days), while the time from illness onset to sampling was not significantly different. T-cell responses in the PP cohort were assayed, analysed and compared with those in the CR and HD cohorts by flow cytometry and ELISpot analysis of peripheral blood mononuclear cells.

Results: Compared with the CR cohort, the proliferation, activation and functional potential of CD8 and CD4 T cells in the PP cohort were not significantly different. However, the frequencies and counts of Teff and Tem in CD8 but not in CD4 T cells of the PP cohort were prominently lower. Moreover, a weaker SARS-CoV-2 N protein-specific IFN-γ T-cell response and a higher frequency of Tregs were detected in the PP cohort.

Conclusion: Suppressed CD8 T-cell differentiation is associated with PP and may be an indicator for the prediction of prolonged SARS-CoV-2 positivity in COVID-19 patients. The association between suppressed CD8 T-cell differentiation and elevated Tregs warrants studies in the future.
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http://dx.doi.org/10.1002/cti2.1259DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7932004PMC
March 2021

Carrier-Free Immobilization of α-Galactosidase as Nano-Biocatalysts for Synthesizing Prebiotic α-Galacto-Oligosaccharides.

Molecules 2021 Feb 25;26(5). Epub 2021 Feb 25.

School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.

α-Galacto-oligosaccharides (α-GOSs) have great functions as prebiotics and therapeutics. This work established the method of batch synthesis of α-GOSs by immobilized α-galactosidase for the first time, laying a foundation for industrial applications in the future. The α-galactosidase from L63 was immobilized as cross-linked enzyme aggregates (CLEAs) nano-biocatalyst through enzyme precipitating and cross-linking steps without using carriers. Among the tested agents, the ammonium sulfate showed high precipitation efficacy and induced regular structures of α-galactosidase CLEAs (Aga-CLEAs) that had been analyzed by scanning electron microscopy and Fourier-transform infrared spectroscopy. Through optimization by response surface methodology, the ammonium sulfate-induced Aga-CLEAs achieved a high activity recovery of around 90% at 0.55 U/mL of enzymes and 36.43 mM glutaraldehyde with cross-linking for 1.71 h. Aga-CLEAs showed increased thermal stability and organic solvent tolerance. The storage ability was also improved since it maintained 74.5% activity after storing at 4 °C for three months, significantly higher than that of the free enzyme (21.6%). Moreover, Aga-CLEAs exhibited excellent reusability in the α-GOSs synthesis from galactose, retaining above 66% of enzyme activity after 10 batch reactions, with product yields all above 30%.
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http://dx.doi.org/10.3390/molecules26051248DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7956481PMC
February 2021

MXene Coupled with CRISPR-Cas12a for Analysis of Endotoxin and Bacteria.

Anal Chem 2021 03 2;93(10):4676-4681. Epub 2021 Mar 2.

Research Center of Molecular Recognition and Biosensing, School of Life Sciences, Shanghai University, Shanghai 200444, P. R. China.

With hydrophilic surface and high density of functional groups, MXene can efficiently adsorb single-stranded DNA to enhance target-induced strand release and quench the fluorescence. Herein, MXene is coupled with CRISPR-Cas12a to sensitively detect LPS and bacteria. Specifically, the aptamer is well designed to initiate the trans-cleavage activity of CRISPR-Cas12a to indiscriminately cleave single-stranded DNA, resulting it to be far away from MXene and the recovery of fluorescence. The target can effectually induce the release of the aptamer strand from the hybrid duplex with the assistance of MXene. The formed aptamer/target complex will inhibit the activation of CRISPR-Cas12a and its trans-cleavage on single-stranded DNA. The established method can selectively and sensitively quantify LPS and Gram-negative bacteria in different samples with detection limits of 11 pg/mL and 23 CFU/mL, respectively. Our study provides a new insight for exploration of universal analytical methods based on MXene coupled with CRISPR-Cas12a.
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http://dx.doi.org/10.1021/acs.analchem.1c00371DOI Listing
March 2021

A deep learning algorithm using CT images to screen for Corona virus disease (COVID-19).

Eur Radiol 2021 Aug 24;31(8):6096-6104. Epub 2021 Feb 24.

Department of Biochemistry and Molecular Biology, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Key Laboratory of Breast Cancer Prevention and Therapy, Ministry of Education, Tianjin Clinical Research Center for Cancer, Tianjin Medical University Cancer Institute and Hospital, Tianjin, 300060, China.

Objective: The outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) has caused more than 26 million cases of Corona virus disease (COVID-19) in the world so far. To control the spread of the disease, screening large numbers of suspected cases for appropriate quarantine and treatment are a priority. Pathogenic laboratory testing is typically the gold standard, but it bears the burden of significant false negativity, adding to the urgent need of alternative diagnostic methods to combat the disease. Based on COVID-19 radiographic changes in CT images, this study hypothesized that artificial intelligence methods might be able to extract specific graphical features of COVID-19 and provide a clinical diagnosis ahead of the pathogenic test, thus saving critical time for disease control.

Methods: We collected 1065 CT images of pathogen-confirmed COVID-19 cases along with those previously diagnosed with typical viral pneumonia. We modified the inception transfer-learning model to establish the algorithm, followed by internal and external validation.

Results: The internal validation achieved a total accuracy of 89.5% with a specificity of 0.88 and sensitivity of 0.87. The external testing dataset showed a total accuracy of 79.3% with a specificity of 0.83 and sensitivity of 0.67. In addition, in 54 COVID-19 images, the first two nucleic acid test results were negative, and 46 were predicted as COVID-19 positive by the algorithm, with an accuracy of 85.2%.

Conclusion: These results demonstrate the proof-of-principle for using artificial intelligence to extract radiological features for timely and accurate COVID-19 diagnosis.

Key Points: • The study evaluated the diagnostic performance of a deep learning algorithm using CT images to screen for COVID-19 during the influenza season. • As a screening method, our model achieved a relatively high sensitivity on internal and external CT image datasets. • The model was used to distinguish between COVID-19 and other typical viral pneumonia, both of which have quite similar radiologic characteristics.
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http://dx.doi.org/10.1007/s00330-021-07715-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7904034PMC
August 2021

Low-Grade Nasopharyngeal Papillary Adenocarcinoma: A Review of 28 Patients in a Single Institution.

Cancer Manag Res 2021 10;13:1271-1278. Epub 2021 Feb 10.

Department of Otolaryngology, Eye and ENT Hospital of Fudan University, Shanghai, 200031, People's Republic of China.

Purpose: Low-grade nasopharyngeal papillary adenocarcinoma (LGNPPA) is a rare nasopharyngeal tumor. This study aimed to analyze the clinical and histopathological features of the disease, and to share our experience of its treatment.

Patients And Methods: We collected demographic data, clinical symptoms, tumor location, pathological features, immunohistochemical results, treatments, and outcomes of 28 patients with pathologically confirmed LGNPPA between 2009 and 2019.

Results: The median age of the 28 patients was 41.5 years, with a female: male ratio of 1.5:1 (17 females, 11 males). The most common symptom was blood-stained rhinorrhea. The neoplasms were located on the roof of the nasopharynx (RON) in 13 patients, the posterior margin of the nasal septum (PMONP) in 12 patients, the lateral wall of the nasopharynx in one case, and both the RON and PMONP in two patients. Fourteen patients were diagnosed with thyroid-like LGNPPA. Immunohistochemically, the tumors were uniformly positive for cytokeratin 7, cytokeratin 8, vimentin, epithelial membrane antigen, and pan-cytokeratin, and negative for thyroglobulin. Twenty-three patients underwent pure endoscopic surgery, three patients underwent preoperative radiotherapy, and two patients underwent radiotherapy postoperatively. All patients were alive without evidence of lymphatic or distant metastases in the follow-up period (range: 7 to 121 months). Two patients (7%, 2/28) experienced disease recurrence.

Conclusion: LGNPPA is an indolent tumor with an excellent prognosis. Endonasal endoscopic excision was an effective treatment. It is important to distinguish thyroid-like LGNPPA from metastatic papillary thyroid carcinoma because these diseases have similar microscopic features but different prognoses.
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http://dx.doi.org/10.2147/CMAR.S288007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7882443PMC
February 2021

Risk of second primary malignancy after minor salivary gland cancer: A Surveillance, Epidemiology, and End Results database analysis.

Head Neck 2021 06 15;43(6):1769-1779. Epub 2021 Feb 15.

Department of Otolaryngology, Eye, Ear, Nose, and Throat Hospital, Fudan University, Shanghai, China.

Background: Minor salivary gland cancer (MiSGC) is a group of tumors with varied disease course in the head and neck. We evaluated the risk of a second primary malignancy (SPM) in MiSGC patients and identified possible prognostic factors for survival using a large population database.

Methods: We used the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data to evaluate the risk and prognosis of SPM in patients diagnosed with MiSGC.

Results: The risk of SPM increased in MiSGC patients compared with the endemic rate. The risk of SPM was slightly greater in female patients and who underwent radiotherapy. Age at primary diagnosis, sex, race, year of diagnosis, SEER stage, radiotherapy, SPM, histology, and tumor site were significant survival prognostic indicators of MiSGC patients.

Conclusion: Radiotherapy and female sex were risk factors for SPM after MiSGC. Long-term surveillance for SPM was important in MiSGC patients.
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http://dx.doi.org/10.1002/hed.26641DOI Listing
June 2021

Alterations in Phenotypes and Responses of T Cells Within 6 Months of Recovery from COVID-19: A Cohort Study.

Virol Sin 2021 Feb 9. Epub 2021 Feb 9.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, CAS, Wuhan, 430071, China.

The COVID-19 pandemic, caused by the SARS-CoV-2 infection, is a global health crisis. While many patients have clinically recovered, little is known about long-term alterations in T cell responses of COVID-19 convalescents. In this study, T cell responses in peripheral blood mononuclear cells of a long-time COVID-19 clinically recovered (20-26 weeks) cohort (LCR) were measured via flow cytometry and ELISpot. The T cell responses of LCR were comparatively analyzed against an age and sex matched short-time clinically recovered (4-9 weeks) cohort (SCR) and a healthy donor cohort (HD). All volunteers were recruited from Wuhan Jinyintan Hospital, China. Phenotypic analysis showed that activation marker PD-1 expressing on CD4 T cells of LCR was still significantly lower than that of HD. Functional analysis indicated that frequencies of Tc2, Th2 and Th17 in LCR were comparable to those of HD, but Tc17 was higher than that of HD. In LCR, compared to the HD, there were fewer IFN-γ producing T cells but more IL-2 secreting T cells. In addition, the circulating Tfh cells in LCR were still slightly lower compared to HD, though the subsets composition had recovered. Remarkably, SARS-CoV-2 specific T cell responses in LCR were comparable to that of SCR. Collectively, T cell responses experienced long-term alterations in phenotype and functional potential of LCR cohort. However, after clinical recovery, SARS-CoV-2 specific T cell responses could be sustained at least for six months, which may be helpful in resisting re-infection.
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http://dx.doi.org/10.1007/s12250-021-00348-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871951PMC
February 2021

Genomic landscape of cutaneous follicular lymphomas reveals 2 subgroups with clinically predictive molecular features.

Blood Adv 2021 02;5(3):649-661

Department of Pathology, Massachusetts General Hospital, Boston, MA.

Primary cutaneous follicle center lymphomas (PCFCLs) are indolent B-cell lymphomas that predominantly remain skin restricted and manageable with skin-directed therapy. Conversely, secondary cutaneous involvement by usual systemic follicular lymphoma (secondary cutaneous follicular lymphoma [SCFL]) has a worse prognosis and often necessitates systemic therapy. Unfortunately, no histopathologic or genetic features reliably differentiate PCFCL from SCFL at diagnosis. Imaging may miss low-burden internal disease in some cases of SCFLs, leading to misclassification as PCFCL. Whereas usual systemic FL is well characterized genetically, the genomic landscapes of PCFCL and SCFL are unknown. Herein, we analyzed clinicopathologic and immunophenotypic data from 30 cases of PCFCL and 10 of SCFL and performed whole-exome sequencing on 18 specimens of PCFCL and 6 of SCFL. During a median follow-up of 7 years, 26 (87%) of the PCFCLs remained skin restricted. In the remaining 4 cases, systemic disease developed within 3 years of diagnosis. Although the SCFLs universally expressed BCL2 and had BCL2 rearrangements, 73% of the PCFCLs lacked BCL2 expression, and only 8% of skin-restricted PCFCLs had BCL2 rearrangements. SCFLs showed low proliferation fractions, whereas 75% of PCFCLs had proliferation fractions >30%. Of the SCFLs, 67% had characteristic loss-of-function CREBBP or KMT2D mutations vs none in skin-restricted PCFCL. Both SCFL and skin-restricted PCFCL showed frequent TNFRSF14 loss-of-function mutations and copy number loss at chromosome 1p36. These data together establish PCFCL as a unique entity with biological features distinct from usual systemic FL and SCFL. We propose 3 criteria based on BCL2 rearrangement, chromatin-modifying gene mutations (CREBBP, KMT2D, EZH2, and EP300), and proliferation index to classify cutaneous FL specimens based on the likelihood of concurrent or future systemic spread.
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http://dx.doi.org/10.1182/bloodadvances.2020002469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876877PMC
February 2021

Genomic landscape of cutaneous follicular lymphomas reveals 2 subgroups with clinically predictive molecular features.

Blood Adv 2021 02;5(3):649-661

Department of Pathology, Massachusetts General Hospital, Boston, MA.

Primary cutaneous follicle center lymphomas (PCFCLs) are indolent B-cell lymphomas that predominantly remain skin restricted and manageable with skin-directed therapy. Conversely, secondary cutaneous involvement by usual systemic follicular lymphoma (secondary cutaneous follicular lymphoma [SCFL]) has a worse prognosis and often necessitates systemic therapy. Unfortunately, no histopathologic or genetic features reliably differentiate PCFCL from SCFL at diagnosis. Imaging may miss low-burden internal disease in some cases of SCFLs, leading to misclassification as PCFCL. Whereas usual systemic FL is well characterized genetically, the genomic landscapes of PCFCL and SCFL are unknown. Herein, we analyzed clinicopathologic and immunophenotypic data from 30 cases of PCFCL and 10 of SCFL and performed whole-exome sequencing on 18 specimens of PCFCL and 6 of SCFL. During a median follow-up of 7 years, 26 (87%) of the PCFCLs remained skin restricted. In the remaining 4 cases, systemic disease developed within 3 years of diagnosis. Although the SCFLs universally expressed BCL2 and had BCL2 rearrangements, 73% of the PCFCLs lacked BCL2 expression, and only 8% of skin-restricted PCFCLs had BCL2 rearrangements. SCFLs showed low proliferation fractions, whereas 75% of PCFCLs had proliferation fractions >30%. Of the SCFLs, 67% had characteristic loss-of-function CREBBP or KMT2D mutations vs none in skin-restricted PCFCL. Both SCFL and skin-restricted PCFCL showed frequent TNFRSF14 loss-of-function mutations and copy number loss at chromosome 1p36. These data together establish PCFCL as a unique entity with biological features distinct from usual systemic FL and SCFL. We propose 3 criteria based on BCL2 rearrangement, chromatin-modifying gene mutations (CREBBP, KMT2D, EZH2, and EP300), and proliferation index to classify cutaneous FL specimens based on the likelihood of concurrent or future systemic spread.
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http://dx.doi.org/10.1182/bloodadvances.2020002469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7876877PMC
February 2021

A Lightweight Internet Sharing Scheme for Sectional Medical Images according to Existing Hospital Network Facilities and Basic Information Security Rules.

J Healthc Eng 2020 4;2020:8838390. Epub 2020 Dec 4.

College of Biomedical Engineering and Imaging Medicine, Army Medical University, Chongqing, China.

Background: With the outbreak of COVID-19, large-scale telemedicine applications can play an important role in the epidemic areas or less developed areas. However, the transmission of hundreds of megabytes of Sectional Medical Images (SMIs) from hospital's Intranet to the Internet has the problems of efficiency, cost, and security. This article proposes a novel lightweight sharing scheme for permitting Internet users to quickly and safely access the SMIs from a hospital using an Internet computer anywhere but without relying on a virtual private network or another complex deployment.

Methods: A four-level endpoint network penetration scheme based on the existing hospital network facilities and information security rules was proposed to realize the secure and lightweight sharing of SMIs over the Internet. A "Master-Slave" interaction to the interactive characteristics of multiplanar reconstruction and maximum/minimum/average intensity projection was designed to enhance the user experience. Finally, a prototype system was established.

Results: When accessing SMIs with a data size ranging from 251.6 to 307.04 MB with 200 kBps client bandwidth (extreme test), the network response time to each interactive request remained at approximately 1 s, the original SMIs were kept in the hospital, and the deployment did not require a complex process; the imaging quality and interactive experience were recognized by radiologists.

Conclusions: This solution could serve Internet medicine at a low cost and may promote the diversified development of mobile medical technology. Under the current COVID-19 epidemic situation, we expect that it could play a low-cost and high-efficiency role in remote emergency support.
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http://dx.doi.org/10.1155/2020/8838390DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737442PMC
January 2021

Dynamics of denitrification performance and denitrifying community under high-dose acute oxytetracycline exposure and various biorecovery strategies in polycaprolactone-supported solid-phase denitrification.

J Environ Manage 2021 Feb 9;279:111763. Epub 2020 Dec 9.

College of Civil Engineering and Architecture, Zhejiang University of Technology, Hangzhou, 310014, PR China.

Solid-phase denitrification (SPD) is a promising technology for nitrate-rich water purification. This study aimed to examine the variation in denitrification performance and denitrifying community under high-dose acute oxytetracycline (OTC) exposure and various biorecovery strategies. The denitrification performance was impaired significantly after one-day OTC shock at 50 mg L in a continuous-flow SPD system supported by a polycaprolactone (PCL) carrier but could rapidly recover without the addition of OTC. When 50 mg L OTC stress was applied for a longer time in the batch tests, a natural recovery period of more than 20 days was required to reach more than 95% nitrate reduction. Under the same conditions, the addition of both mature biofilm-attached PCL carrier and fresh biofilm-free PCL carrier significantly shortened the recovery time for efficient nitrate reduction, mainly due to the increase in organic availability from the PCL carriers. However, the composition of the microbial community notably changed due to the effects of OTC according to high-throughput sequencing and metagenomic analysis. Genes encoding NAR and NIR were much more sensitive than those encoding NOR and NOS to OTC shock. Tetracycline resistance gene (TRG) enrichment was 15.86% higher in the biofilm that experienced short-term OTC shock than in the control biofilm in the continuous-flow SPD system.
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http://dx.doi.org/10.1016/j.jenvman.2020.111763DOI Listing
February 2021

Development and validation of a postoperative nomogram for predicting overall survival after endoscopic surgical management of olfactory neuroblastoma.

EClinicalMedicine 2020 Dec 30;29-30:100577. Epub 2020 Nov 30.

Department of Otolaryngology, Eye and ENT Hospital, Fudan University, Shanghai 200031, PR China.

Background: Olfactory neuroblastoma (ONB) is a rare malignancy arising in the nasal vault. Endoscopic resection has been reported to improve overall survival (OS). At present, clinicopathological predictors of the prognosis of ONB remain undefined.

Methods: Data including demographics, clinical characteristics and follow-up information of ONB patients treated with endoscopic surgery were collected. Risk factors on OS rates were investigated by LASSO and Cox analyses. A nomogram was developed and evaluated with internal validation. Risk groups were established according to patients' points in the nomogram.

Findings: 154 ONB patients treated with surgery were included in this single center study. A nomogram based on multivariate Cox regression model including multiple tumor history, orbital invasion, carotid canal invasion, modified Kadish stage, delivery sequence of RT and surgery, sequence of chemotherapy and surgery was developed. The bias-corrected C-index (0.886 [95% CI: 0.843-0.943]) was significantly higher than of conventional staging classifications. The AUC of nomogram regarding 1-, 2- and 5-year OS probabilities reached 0.912, 0.929 and 0.957, respectively. The risk levels based on nomogram points were more discriminative than conventional classifications.

Interpretation: Validation analysis showed good predictive accuracy and discriminative ability of the nomogram. Therefore, the nomogram could be utilized to individually predict survival probability for ONB patients after endoscopic resection.

Funding: This study was funded by the Chinese Academy of Medical Sciences (No. 2019-I2M-5-003), the Shanghai Science and Technology Commission (No. 19411950600), the Shanghai Hospital Development Center (No. SHDC12018118) and the Eye, Ear, Nose and Throat Hospital of Fudan University (No. SYB202006).
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http://dx.doi.org/10.1016/j.eclinm.2020.100577DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7711220PMC
December 2020
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