Publications by authors named "Tao Hu"

781 Publications

Role of genetics in amyotrophic lateral sclerosis: a large cohort study in Chinese mainland population.

J Med Genet 2021 Sep 20. Epub 2021 Sep 20.

Department of Neurology, Neurological Diseases and Brain Function Laboratory, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Background: A large number of new causative and risk genes for amyotrophic lateral sclerosis (ALS) have been identified mostly in patients of European ancestry. In contrast, we know relatively little regarding the genetics of ALS in other ethnic populations. This study aims to provide a comprehensive analysis of the genetics of ALS in an unprecedented large cohort of Chinese mainland population and correlate with the clinical features of rare variants carriers.

Methods: A total of 1587 patients, including 64 familial ALS (FALS) and 1523 sporadic ALS (SALS), and 1866 in-house controls were analysed by whole-exome sequencing and/or testing for G4C2 repeats in . Forty-one ALS-associated genes were analysed.

Findings: 155 patients, including 26 (40.6%) FALS and 129 (8.5%) SALS, carrying rare pathogenic/likely pathogenic (P/LP) variants of ALS causative genes were identified. was the most common mutated gene, followed by , , , and . By burden analysis, rare variants in , and contributed to the collective risk for ALS (p<2.5e-6) at the gene level, but at the allelic level p.Gly294Val and p.Arg521Cys and p.Arg521His were the most important single variants causing ALS. Clinically, P/LP variants in and were associated with poor prognosis, in linked with younger age of onset, and repeats tended to affect cognition.

Conclusions: Our data provide essential information for understanding the genetic and clinical features of ALS in China and for optimal design of genetic testing and evaluation of disease prognosis.
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http://dx.doi.org/10.1136/jmedgenet-2021-107965DOI Listing
September 2021

A predictive nomogram: a cross-sectional study on a simple-to-use model for screening 12-year-old children for severe caries in middle schools.

BMC Oral Health 2021 Sep 20;21(1):457. Epub 2021 Sep 20.

Department of Preventive Dentistry, State Key Laboratory of Oral Diseases, National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, Sichuan, China.

Background: A nomogram is a tool that transforms complex regression equations into simple and visual graphs and enables clinicians and patients to conveniently compute output probabilities without needing medical knowledge and complex formulas. The aim of this study was to develop and validate a predictive nomogram to screen for severe caries among 12-year-old children based on risk factors in Sichuan Province, China.

Methods: A cross-sectional study of 4573 12-year-olds was conducted up to May 2016 in middle schools from three districts and three counties in Sichuan Province, China. All the children underwent oral examinations and completed questionnaires to assess general information, oral impacts on daily performance, dietary habits, subjective health conditions, history of dental trauma, frequency of toothache, dental visits, and knowledge, attitudes, and behaviours toward oral hygiene. Univariate analysis and multivariate logistic regression analysis were used to determine which variables were significantly associated with severe caries (operationalized as DMFT ≥ 3). A nomogram was developed and validated by using the 'rms' package and two cross-validation methods.

Results: Severe caries was found in 537 of the 4573 children (11.74%). Multivariate logistic regression analysis revealed that the following variables predicted a higher risk of severe caries: 'female' [odds ratio (OR) = 1.985, 95% confidence interval (95% CI): 1.63-2.411], 'urban' (OR = 2.389, 95% CI: 1.96-2.91), 'non-only child' (OR = 1.317, 95% CI: 1.07-1.625), 'very poor self-assessment of oral health status' (OR = 2.157, 95% CI: 1.34-3.467) and 'visited a dentist less than 6 months' (OR = 1.861, 95% CI: 1.38-2.505). Multivariate logistic regression analysis also indicated that the following variables predicted a lower risk of severe caries: 'middle level of urbanization' (OR = 0.395, 95% CI: 0.32-0.495) and 'high level of urbanization' (OR = 0.466, 95% CI: 0.37-0.596). Both the fivefold and leave-one-out cross-validation methods indicated that the nomogram model built by these 6 variables displayed good disease recognition ability.

Conclusions: The nomogram was a simple-to-use model to screen children for severe caries. This model was found to facilitate non-dental professionals in assessing risk values without oral examinations and making referrals to dental professionals.
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http://dx.doi.org/10.1186/s12903-021-01819-2DOI Listing
September 2021

Kinetic resolution of -aryl β-amino alcohols asymmetric aminations of anilines.

Chem Commun (Camb) 2021 Sep 16;57(74):9394-9397. Epub 2021 Sep 16.

School of Physical Science and Technology, ShanghaiTech University, Shanghai 201210, China.

An efficient kinetic resolution of -aryl β-amino alcohols has been developed asymmetric -aminations of anilines with azodicarboxylates enabled by chiral phosphoric acid catalysis. Broad substrate scope and high kinetic resolution performances were afforded with this method. Control experiments supported the critical roles of the NH and OH group in these reactions.
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http://dx.doi.org/10.1039/d1cc03117aDOI Listing
September 2021

Sodium-Based Dual-Ion Battery Based on the Organic Anode and Ionic Liquid Electrolyte.

ACS Appl Mater Interfaces 2021 Sep 14. Epub 2021 Sep 14.

School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou 510640, China.

Combining the advantages of dual-ion batteries (DIBs) and sodium-ion batteries (SIBs), we herein develop a superior sodium-based dual-ion battery (Na-DIB) based on the PTCDA organic anode and ionic liquid (IL) electrolyte. The system shows the highest specific discharge capacity of 177 mAh g at 0.5C and excellent capacity retention over 100% at 2C after 200 cycles. Notably, even at an ultrahigh rate of 20C, the battery still maintains a considerable capacity of 60 mAh g with a coulombic efficiency (CE) close to 100 and 94% capacity retention after 1000 cycles. Moreover, the self-discharge of the system has been investigated and shown to have an extremely low value of 0.18% h. Consequently, this work presents an excellent Na-DIB system, which could be a promising candidate for large-scale applications.
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http://dx.doi.org/10.1021/acsami.1c10836DOI Listing
September 2021

Lipid Accumulation Product Combined With Urine Glucose Excretion Improves the Efficiency of Diabetes Screening in Chinese Adults.

Front Endocrinol (Lausanne) 2021 23;12:691849. Epub 2021 Aug 23.

Department of Endocrinology, Zhongda Hospital, Institute of Diabetes, Medical School, Southeast University, Nanjing, China.

Background: To compare the efficacy of lipid accumulation product (LAP) and urine glucose excretion (UGE) in predicting diabetes and evaluate whether the combination of LAP and UGE would help to improve the efficacy of using LAP alone or UGE alone in identifying diabetes.

Methods: Data from 7485 individuals without prior history of diabetes who participated in a cross-sectional survey in Jiangsu, China, were analyzed. Each participant underwent an oral glucose-tolerance test. Operating characteristic curves (ROC) and logistic regression analyses were used to evaluate the performance of LAP and UGE in identification of newly diagnosed diabetes (NDM) and prediabetes (PDM).

Results: For subjects with NDM, the area under the ROC curve was 0.72 for LAP and 0.85 for UGE, whereas for PDM, these values were 0.62 and 0.61, respectively. Furthermore, LAP exhibited a comparable sensitivity with UGE in detecting NDM (76.4% 76.2%, p = 0.31). In predicting PDM, LAP showed a higher sensitivity than UGE (66.4% 42.8%, p < 0.05). The combination of LAP and UGE demonstrated a significantly higher sensitivity than that of LAP alone and UGE alone for identification of NDM (93.6%) and PDM (80.1%). Moreover, individuals with both high LAP and high UGE had significantly increased risk of NDM and PDM than those with both low LAP and low UGE.

Conclusions: The combination of LAP and UGE substantially improved the efficacy of using LAP and using UGE alone in detecting diabetes, and may be a novel approach for mass screening in the general population.
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http://dx.doi.org/10.3389/fendo.2021.691849DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8419462PMC
August 2021

Metabolite identification of iridin in rats by using UHPLC-MS/MS and pharmacokinetic study of its metabolite irigenin.

J Chromatogr B Analyt Technol Biomed Life Sci 2021 Aug 28;1181:122914. Epub 2021 Aug 28.

Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address:

Iridin, one of the main bioactive components isolated from Belamcanda chinensis (L.) DC, exerts various pharmacological activities, such as anti-inflammation, antioxidant, and antitumor. However, the metabolism and pharmacokinetics of iridin are still unknown. After 100 mg/kg administration of iridin orally, the plasma, urine, and fecal bio-samples from Sprague-Dawley (SD) rats were collected and detected by ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The pharmacokinetics of the major metabolite irigenin (aglycon of iridin) and a total of thirteen metabolites of iridin were identified, including five metabolites in plasma, ten metabolites in urine, and six metabolites in feces. The most principal metabolic pathway of iridin was glucuronidation after demethylation and was mediated by UDP-glucuronosyltransferases (UGTs) 1A7, 1A8, 1A9 and 1A10. This study highlights the first-time investigation of the metabolism of iridin in vivo, and the pharmacokinetics of irigenin (the major metabolite of iridin) in rats. These results provide robust evidence for further research and clinical application of iridin.
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http://dx.doi.org/10.1016/j.jchromb.2021.122914DOI Listing
August 2021

Elucidation of Distinct Modular Assemblies of Smoothened Receptor by Bitopic Ligand Measurement.

J Med Chem 2021 Sep 7. Epub 2021 Sep 7.

iHuman Institute, ShanghaiTech University, Ren Building, 393 Middle Huaxia Road, Shanghai 201210, China.

Class F G protein-coupled receptors are characterized by a large extracellular domain (ECD) in addition to the common transmembrane domain (TMD) with seven α-helixes. For smoothened receptor (SMO), structural studies revealed dissected ECD and TMD, and their integrated assemblies. However, distinct assemblies were reported under different circumstances. Using an unbiased approach based on four series of cross-conjugated bitopic ligands, we explore the relationship between the active status and receptor assembly. Different activity dependency on the linker length for these bitopic ligands corroborates the various occurrences of SMO assembly. These results reveal a rigid "near" assembly for active SMO, which is in contrast to previous results. Conversely, inactive SMO adopts a free ECD, which would be remotely captured at "far" assembly by cholesterol. Altogether, we propose a mechanism of cholesterol flow-caused SMO activation involving an erection of ECD from far to near assembly.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01220DOI Listing
September 2021

Rational Remodeling of Atypical Scaffolds for the Design of Photoswitchable Cannabinoid Receptor Tools.

J Med Chem 2021 Sep 3. Epub 2021 Sep 3.

iHuman Institute, ShanghaiTech University, Pudong, Shanghai 201210, China.

Azobenzene-embedded photoswitchable ligands are the widely used chemical tools in photopharmacological studies. Current approaches to azobenzene introduction rely mainly on the isosteric replacement of typical azologable groups. However, atypical scaffolds may offer more opportunities for photoswitch remodeling, which are chemically in an overwhelming majority. Herein, we investigate the rational remodeling of atypical scaffolds for azobenzene introduction, as exemplified in the development of photoswitchable ligands for the cannabinoid receptor 2 (CB2). Based on the analysis of residue-type clusters surrounding the binding pocket, we conclude that among the three representative atypical arms of the CB2 antagonist, AM10257, the adamantyl arm is the most appropriate for azobenzene remodeling. The optimizing spacer length and attachment position revealed with excellent thermal bistability, decent photopharmacological switchability between its two configurations, and high subtype selectivity. This structure-guided approach gave new impetus in the extension of new chemical spaces for tool customization for increasingly diversified photo-pharmacological studies and beyond.
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http://dx.doi.org/10.1021/acs.jmedchem.1c01088DOI Listing
September 2021

A simulation-extrapolation approach for regression analysis of misclassified current status data with the additive hazards model.

Stat Med 2021 Sep 2. Epub 2021 Sep 2.

Department of Statistics, University of Missouri, Columbia, Missouri, USA.

Current status data arise when each subject is observed only once and the failure time of interest is only known to be either smaller or larger than the observation time rather than observed exactly. For the situation, due to the use of imperfect diagnostic tests, the failure status could often suffer misclassification or one observes misclassified data, which may result in severely biased estimation if not taken into account. In this article, we discuss regression analysis of such misclassified current status data arising from the additive hazards model, and a simulation-extrapolation (SIMEX) approach is developed for the estimation. Furthermore, the asymptotic properties of the proposed estimators are established, and a simulation study is conducted to assess the empirical performance of the method, which indicates that the proposed procedure performs well. In particular, it can correct the estimation bias given by the naive method that ignores the existence of misclassification. An application to a medical study on gonorrhea is also provided.
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http://dx.doi.org/10.1002/sim.9184DOI Listing
September 2021

Conjugation of Zika virus EDIII with CRM, 8-arm PEG and mannan for development of an effective Zika virus vaccine.

Int J Biol Macromol 2021 Aug 30;190:713-721. Epub 2021 Aug 30.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China. Electronic address:

Zika virus (ZIKV) induces neurological and autoimmune complications such as microcephaly and Guillain-Barre syndrome. Effective vaccines are necessary to prevent the ZIKV infection. E protein of ZIKV is responsible for virus attachment, entry, and fusion. The domain III of E protein (EDIII) contains the neutralizing epitopes and is ideal to act as an antigen for ZIKV vaccine. However, EDIII is poorly immunogenic. CRM is a carrier protein and can activate T helper cells for EDIII. Mannan is a ligand of TLR-4 or TLR-2. Eight-arm PEG can link multiple EDIII molecules in one entity. In the present study, EDIII was covalently conjugated with CRM, 8-arm PEG and mannan to improve the immunogenicity of EDIII. The conjugate (CRM-EDIII-PM) elicited high EDIII-specific antibody titers in the BALB/c mice. Th1-type cytokines (IFN-γ and IL-2) and Th2-type cytokines (IL-5 and IL-10) were secreted at a marked level. Thus, CRM-EDIII-PM could stimulate potent humoral and cellular immune response to EDIII. The serum exposure of CRM-EDIII-PM to the immune system was prolonged. Moreover, CRM-EDIII-PM did not lead to apparent toxicity to the organs. Therefore, CRM-EDIII-PM was expected as a promising vaccine candidate for its ability to induce strong immune responses.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.08.177DOI Listing
August 2021

2021 Taxonomic update of phylum Negarnaviricota (Riboviria: Orthornavirae), including the large orders Bunyavirales and Mononegavirales.

Arch Virol 2021 Aug 31. Epub 2021 Aug 31.

RNA Viruses Section, Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

In March 2021, following the annual International Committee on Taxonomy of Viruses (ICTV) ratification vote on newly proposed taxa, the phylum Negarnaviricota was amended and emended. The phylum was expanded by four families (Aliusviridae, Crepuscuviridae, Myriaviridae, and Natareviridae), three subfamilies (Alpharhabdovirinae, Betarhabdovirinae, and Gammarhabdovirinae), 42 genera, and 200 species. Thirty-nine species were renamed and/or moved and seven species were abolished. This article presents the updated taxonomy of Negarnaviricota as now accepted by the ICTV.
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http://dx.doi.org/10.1007/s00705-021-05143-6DOI Listing
August 2021

Three Novel Avastroviruses Identified in Dead Wild Crows.

Virol Sin 2021 Aug 30. Epub 2021 Aug 30.

CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Center for Influenza Research and Early-Warning (CASCIRE), CAS-TWAS Center of Excellence for Emerging Infectious Diseases (CEEID), Chinese Academy of Sciences, Beijing, 100101, China.

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http://dx.doi.org/10.1007/s12250-021-00416-5DOI Listing
August 2021

N130, N175 and N207 are N-linked glycosylation sites of duck Tembusu virus NS1 that are important for viral multiplication, viremia and virulence in ducklings.

Vet Microbiol 2021 Oct 25;261:109215. Epub 2021 Aug 25.

Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang District, Chengdu City, Sichuan Province, 611130, China; Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang District, Chengdu City, Sichuan Province, 611130, China; Key Laboratory of Animal Disease and Human Health of Sichuan Province, Wenjiang District, Chengdu City, Sichuan Province, 611130, China. Electronic address:

Duck Tembusu virus (DTMUV) is an emerging mosquito-borne flavivirus that has caused acute egg-drop syndrome in egg-laying ducks. DTMUV nonstructural protein 1 (NS1) contains three potential predicted N-linked glycosylation sites at residues 130, 175 and 207. In this study, we found that mutations at these sites affect the molecular weight of recombinant NS1, as assessed by western blot assays; however, the mutations do not affect their subcellular localization in the cytoplasm, as assessed by colocalization assays. Four recombinant viruses substituting the asparagine (N) residues at N130, N175, N207 or N130/N175/N207 of NS1 with alanine (A) residues were generated using rDTMUV-i, an infectious cDNA clone of the DTMUV CQW1 strain. Deglycosylation assays of the mutant virus NS1 were performed using endoglycosidases Endo H or PNGase F treatment in both mammalian and avian cells. The NS1-WT, NS1-N130A, NS1-N175A and NS1-N207A showed a shift in migration to 37 kDa after digestion with both endoglycosidases, which further confirmed that N130, N175 and N207 were the glycosylation sites of DTMUV NS1. Compared to the parental rDTMUV, the single mutants impaired viral multiplication in vitro, while the nonglycosylated virus rDTMUV-NS1-N130A/N175A/N207A showed a 5-fold to 178-fold decrease in viral titers and smaller plaque sizes. Notably, all mutant viruses were still highly virulent to duck embryos, but the embryos inoculated with rDTMUV-NS1-N130A/N175A/N207A started to die on the fourth day, which exhibited a prolonged time to death compared to that of rDTMUV. Moreover, rDTMUV-NS1-N130A/N175A/N207A was attenuated in vivo, showing no mortality and producing significantly lower viral titers in heart, spleen, kidney, brain and thymus as well as 2-fold to 3-fold lower viremia at 3 and 5 days post infection. Overall, our results indicated that N130, N175 and N207 are N-linked glycosylation sites of DTMUV NS1, which play crucial roles in viral multiplication, viremia and virulence in vitro and in vivo.
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http://dx.doi.org/10.1016/j.vetmic.2021.109215DOI Listing
October 2021

Characterizing microRNA-mediated modulation of gene expression noise and its effect on synthetic gene circuits.

Cell Rep 2021 Aug;36(8):109573

Ministry of Education Key Laboratory of Bioinformatics; Center for Synthetic and Systems Biology; Bioinformatics Division, Beijing National Research Center for Information Science and Technology; Department of Automation, Tsinghua University, Beijing 100084, China. Electronic address:

MicroRNAs (miRNAs) have been shown to modulate gene expression noise, but less is known about how miRNAs with different properties may regulate noise differently. Here, we investigate the role of competing RNAs and the composition of miRNA response elements (MREs) in modulating noise. We find that weak competing RNAs could introduce lower noise than strong competing RNAs. In comparison with a single MRE, both repetitive and composite MREs can reduce the noise at low expression, but repetitive MREs can elevate the noise remarkably at high expression. We further observed the behavior of a synthetic cell-type classifier with miRNAs as inputs and find that miRNAs and MREs that could introduce higher noise tend to enhance cell state transition. These results provide a systematic and quantitative understanding of the function of miRNAs in controlling gene expression noise and the utilization of miRNAs to modulate the behavior of synthetic gene circuits.
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http://dx.doi.org/10.1016/j.celrep.2021.109573DOI Listing
August 2021

Catalytically Cleavable Detergent for Membrane Protein Studies.

ACS Omega 2021 Aug 4;6(32):21087-21093. Epub 2021 Aug 4.

iHuman Institute, ShanghaiTech University, Y Building, 393 Middle Huaxia Road, Shanghai 201210, China.

Throughout the studies of membrane proteins (MPs), proper detergents are essential for the preparation of stable aqueous samples. To date, universally applicable detergents have not yet been reported to accommodate the distinct requirements for the highly diversified MPs and at the different stages of MP manipulation. Detergent exchange often has to be performed. We report herein the catalytically cleavable detergents (CatCDs) that can be efficiently removed to facilitate a complete exchange. To this end, functional groups, like propargyl and allyl, are introduced as branched chains or built in the hydrophobic chain close to the hydrophilic head. The representative CatCDs can be used as usual detergents in the extraction and purification of MPs and later be removed upon the addition of catalytic palladium. Mediated by , reconstitution of a transporter protein MsbA into a series of detergents was achieved. The extension of these designs could facilitate the future optimization of other biophysics studies.
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http://dx.doi.org/10.1021/acsomega.1c02894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8375090PMC
August 2021

Replication/Assembly Defective Avian Flavivirus With Internal Deletions in the Capsid Can Be Used as an Approach for Living Attenuated Vaccine.

Front Immunol 2021 4;12:694959. Epub 2021 Aug 4.

Institute of Preventive Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Avian Tembusu virus (TMUV) is a novel flavivirus causing severe egg drop and fatal encephalitis in avian in Asia. In the present study, we screened the structural and functional requirements of TMUV capsid protein (CP) for viral morphogenesis using reverse genetics methods in combination with replicon packaging assays. TMUV-CP showed dramatic functional and structural flexibility, and even though 44 residues were removed from the N-terminus, it was still capable of packaging replicon RNA; in addition, 33 residues were deleted from the C-terminus (containing nearly the entire α4-helix), and infectious particles were still produced, although α4-α4' is supposedly vital for CP dimerization and nucleocapsid formation. We further analyzed two mutants (ΔC20-43 and ΔC64-96 viruses) with relatively large deletions that still replicated well in BHK-21 cells. Our data indicate that internal deletions within CP impaired viral replication or assembly, resulting in attenuated virus proliferation in cells and attenuated virulence in duck embryos, and these deletion mutations are quite stable in cell culture. An assay indicated that both ΔC20-43 virus and ΔC64-96 virus were highly attenuated in ducklings but still immunogenic. Single-dose immunization with ΔC20-43 virus or ΔC64-96 virus could protect ducklings from a lethal challenge with good antigen clearance. Together, our data shed light on replication/assembly defective TMUV with internal deletions in CP and provide an effective approach to attenuate viral virulence in live vaccines without changing the antigen composition.
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http://dx.doi.org/10.3389/fimmu.2021.694959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8371329PMC
August 2021

Revascularization by percutaneous coronary intervention in a case of left main coronary artery atresia.

Catheter Cardiovasc Interv 2021 Aug 19. Epub 2021 Aug 19.

Department of Cardiology, Xijing Hospital, Air Force Medical University, China.

Left main coronary artery atresia (LMCAA) is a rare congenital anomaly of the coronary artery that may have an unfavorable prognosis if left untreated. Surgical revascularization by either coronary artery bypass grafting or coronary reconstruction osteoplasty is unanimously recognized as the treatment of choice for this condition. Here, we first report a case of LMCAA treated with revascularization by percutaneous coronary intervention (PCI) through a retrograde approach. Intravascular ultrasound revealed an unusual coronary structure for the left main artery. PCI appears to be a feasible and effective alternative to surgery for the treatment of LMCAA, particularly if a minimally invasive method is desired.
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http://dx.doi.org/10.1002/ccd.29931DOI Listing
August 2021

Correction to: Integrative taxonomy and molecular phylogeny of three poorly known tintinnine ciliates, with the establishment of a new genus (Protista; Ciliophora; Oligotrichea).

BMC Ecol Evol 2021 Aug 11;21(1):158. Epub 2021 Aug 11.

College of Fisheries, & Key Laboratory of Mariculture, Ministry of Education, Ocean University of China, Qingdao, 266003, China.

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http://dx.doi.org/10.1186/s12862-021-01875-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8359533PMC
August 2021

ODT FLOW: Extracting, analyzing, and sharing multi-source multi-scale human mobility.

PLoS One 2021 5;16(8):e0255259. Epub 2021 Aug 5.

Department of Health Promotion, Education, and Behavior, University of South Carolina, Columbia, South Carolina, United States of America.

In response to the soaring needs of human mobility data, especially during disaster events such as the COVID-19 pandemic, and the associated big data challenges, we develop a scalable online platform for extracting, analyzing, and sharing multi-source multi-scale human mobility flows. Within the platform, an origin-destination-time (ODT) data model is proposed to work with scalable query engines to handle heterogenous mobility data in large volumes with extensive spatial coverage, which allows for efficient extraction, query, and aggregation of billion-level origin-destination (OD) flows in parallel at the server-side. An interactive spatial web portal, ODT Flow Explorer, is developed to allow users to explore multi-source mobility datasets with user-defined spatiotemporal scales. To promote reproducibility and replicability, we further develop ODT Flow REST APIs that provide researchers with the flexibility to access the data programmatically via workflows, codes, and programs. Demonstrations are provided to illustrate the potential of the APIs integrating with scientific workflows and with the Jupyter Notebook environment. We believe the platform coupled with the derived multi-scale mobility data can assist human mobility monitoring and analysis during disaster events such as the ongoing COVID-19 pandemic and benefit both scientific communities and the general public in understanding human mobility dynamics.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0255259PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8341631PMC
August 2021

Revealing Public Opinion Towards COVID-19 Vaccines With Twitter Data in the United States: Spatiotemporal Perspective.

J Med Internet Res 2021 09 10;23(9):e30854. Epub 2021 Sep 10.

Geoinformation and Big Data Research Laboratory, Department of Geography, University of South Carolina, Columbia, SC, United States.

Background: The COVID-19 pandemic has imposed a large, initially uncontrollable, public health crisis both in the United States and across the world, with experts looking to vaccines as the ultimate mechanism of defense. The development and deployment of COVID-19 vaccines have been rapidly advancing via global efforts. Hence, it is crucial for governments, public health officials, and policy makers to understand public attitudes and opinions towards vaccines, such that effective interventions and educational campaigns can be designed to promote vaccine acceptance.

Objective: The aim of this study was to investigate public opinion and perception on COVID-19 vaccines in the United States. We investigated the spatiotemporal trends of public sentiment and emotion towards COVID-19 vaccines and analyzed how such trends relate to popular topics found on Twitter.

Methods: We collected over 300,000 geotagged tweets in the United States from March 1, 2020 to February 28, 2021. We examined the spatiotemporal patterns of public sentiment and emotion over time at both national and state scales and identified 3 phases along the pandemic timeline with sharp changes in public sentiment and emotion. Using sentiment analysis, emotion analysis (with cloud mapping of keywords), and topic modeling, we further identified 11 key events and major topics as the potential drivers to such changes.

Results: An increasing trend in positive sentiment in conjunction with a decrease in negative sentiment were generally observed in most states, reflecting the rising confidence and anticipation of the public towards vaccines. The overall tendency of the 8 types of emotion implies that the public trusts and anticipates the vaccine. This is accompanied by a mixture of fear, sadness, and anger. Critical social or international events or announcements by political leaders and authorities may have potential impacts on public opinion towards vaccines. These factors help identify underlying themes and validate insights from the analysis.

Conclusions: The analyses of near real-time social media big data benefit public health authorities by enabling them to monitor public attitudes and opinions towards vaccine-related information in a geo-aware manner, address the concerns of vaccine skeptics, and promote the confidence that individuals within a certain region or community have towards vaccines.
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http://dx.doi.org/10.2196/30854DOI Listing
September 2021

FaHSP17.8-CII orchestrates lead tolerance and accumulation in shoots via enhancing antioxidant enzymatic response and PSII activity in tall fescue.

Ecotoxicol Environ Saf 2021 Oct 28;223:112568. Epub 2021 Jul 28.

College of Agriculture, Henan University of Science and Technology, Luoyang, China. Electronic address:

Tall fescue (Festuca arundinacea Schreb.) shows huge potential for lead (Pb) phytoremediation, while little is known on the molecular mechanisms involved in Pb tolerance and accumulation. Here, genetic engineering strategy was firstly used to investigate Pb tolerance and accumulation in tall fescue. The transgenic tall fescue overexpressing a class II (CII) sHSP gene FaHSP17.8-CII was generated. After exposure to 1000 mg/L Pb(NO), two FaHSP17.8-CII overexpressing lines, OE#3 and OE#7, showed higher tolerance to Pb as illustrated by the reduced levels of electrolyte leakage (EL) and malondialdehyde (MDA) as compared to the wild-type (WT) plants under Pb stress. Moreover, the FaHSP17.8-CII overexpression lines, OE#3 and OE#7, exhibited 36.3% and 46.6% higher shoot Pb accumulation relative to the WT grasses. When the grasses were exposed to Pb stress, the two OE lines had higher CAT, POD and SOD activities as compared to WT. Additionally, overexpression of FaHSP17.8-CII improved the synthesis of chlorophyll and transcript abundance of FapsbC, FapsbD and FapsbE, and alleviated the photoinhibition of PSII in tall fescue under Pb stress. This study provides an initial genetic engineering strategy to improve Pb phytoremediation efficiency in tall fescue by FaHSP17.8-CII overexpression.
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http://dx.doi.org/10.1016/j.ecoenv.2021.112568DOI Listing
October 2021

Conjugation with inulin improves the environmental stability of haloalkane dehalogenase DhaA.

Enzyme Microb Technol 2021 Sep 21;149:109832. Epub 2021 May 21.

College of Life Sciences, Liaoning Normal University, Dalian, 116081, Liaoning Province, China. Electronic address:

Haloalkane dehalogenase DhaA catalyzes the hydrolytic cleavage of carbon-halogen bonds and produces alcohol, a proton and a halide. However, DhaA suffers from the poor environmental stability, such as sensitivity to high temperature, low pH, hypersaline and organic solvent. In order to improve the environmental stability of DhaA, DhaA was covalently conjugated with inulin, a hydrophilic polysaccharide in the present study. Each DhaA was averagely conjugated with 7∼8 inulin molecules. The conjugated inulin could form a hydration layer around DhaA, which increased the conformational rigidity and decreased the entropy of the enzyme. Conjugation of inulin maintained 75.5 % of the enzymatic activity of DhaA and slightly altered the structure of DhaA. As compared with DhaA, the conjugate (inu-DhaA) showed slightly different kinetic parameters (K of 2.9 μmol/L and K of 1.0 s). Inulin conjugation could delay the structural unfolding and/or slow the protonation process of DhaA under undesirable environment, including the long-term storage, low pH, hypersaline and organic solvent stability. As a result, the environmental stability of DhaA was markedly increased upon conjugation with inulin. Thus, inulin conjugation was an effective approach to enhance the environmental stability of DhaA.
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http://dx.doi.org/10.1016/j.enzmictec.2021.109832DOI Listing
September 2021

Graphene-mediated ferromagnetic coupling in the nickel nano-islands/graphene hybrid.

Sci Adv 2021 Jul 23;7(30). Epub 2021 Jul 23.

State Key Laboratory of Functional Materials for Informatics, Shanghai Institute of Microsystem and Information Technology, Chinese Academy of Sciences, 865 Changning Road, Shanghai 200050, China.

Nanoscale magnetic structures are fundamental to the design and fabrication of spintronic devices and have exhibited tremendous potential superior to the conventional semiconductor devices. However, most of the magnetic moments in nanostructures are unstable due to size effect, and the possible solution based on exchange coupling between nanomagnetism is still not clear. Here, graphene-mediated exchange coupling between nanomagnets is demonstrated by depositing discrete superparamagnetic Ni nano-islands on single-crystal graphene. The heterostructure exhibits ideal two-dimensional (2D) ferromagnetism with clear hysteresis loops and Curie temperature up to 80 K. The intrinsic ferromagnetism in graphene and antiferromagnetic exchange coupling between graphene and Ni nano-islands are revealed by x-ray magnetic circular dichroism and density functional theory calculations. The artificial 2D ferromagnets constitute a platform to study the coupling mechanism between complex correlated electronic systems and magnetism on the nanoscale, and the results and concept provide insights into the realization of spin manipulation in quantum computing.
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http://dx.doi.org/10.1126/sciadv.abg7054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8302123PMC
July 2021

circRNA derived from CLSPN (circCLSPN) is an oncogene in human glioblastoma multiforme by regulating cell growth, migration and invasion via ceRNA pathway.

J Biosci 2021 ;46

Department of Neurosurgery, Renmin Hospital of Wuhan Caidian District, Wuhan, Hubei, China.

Glioblastoma multiforme (GBM) is the most aggressive and prevalent brain tumor in adults. The circRNA derived from CLSPN (hsa_circ_0011591, circCLSPN) is remarkably upregulated in GBM; however its functional role was uncovered yet. First, we examined expression of circCLSPN using GSE109569 database and RT-qPCR, and circCLSPN level was upregulated in human GBM tumor tissues and cells (A172 and LN18); moreover, circCLSPN showed a stable structure stability. Then, a series of loss-of-functional experiments were performed using CCK-8 assay, colony formation assay, flow cytometry, scratch wound assay, and transwell assay. Consequently, circCLSPN silencing suppressed cell viability, colony formation ability, cell cycle progression, migration, and invasion of A172 and LN18 cells , and promoted apoptosis rate. Allied with those were decreased B cell lymphoma-2 (Bcl-2), matrix metalloproteinase-2 (MMP2) and MMP9 expression, and elevated Bcl-2-associated X protein (Bax) level. According to dual-luciferase reporter assay and RNA pull-down assay, miR-370-3p was identified to be targeted and sponged by circCLSPN, and further targeted and negatively regulated USP39. Functionally, overexpressing miR-370-3p could mimic effects of circCLSPN interference. Rescue experiments revealed that blocking miR-370-3p could partially reverse the suppression of circCLSPN knockdown on cell growth, migration and invasion, and role of miR- 370-3p overexpression was abrogated by restoring USP39. , circCLSPN knockdown hindered tumor growth of LN18 cells by affecting miR-370-3p, USP39, MMP2 and MMP9 expression. In conclusion, circCLSPN elicited an oncogenic role in tumorigenesis and malignant progression of human GBM cells through circCLSPN-miR-370-3p-USP39 pathway.
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January 2021

Substitutions at Loop Regions of TMUV E Protein Domain III Differentially Impair Viral Entry and Assembly.

Front Microbiol 2021 28;12:688172. Epub 2021 Jun 28.

Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, China.

Flavivirus envelope protein (E) plays an important role in cellular infection, especially in virulence and antigenicity. E domain III of Tembusu virus (TMUV) is highly conserved among flaviviruses and contains four loop regions. However, the functions of the loop regions of TMUV E domain III in the viral life cycle have not yet been discovered. In this study, using a reverse genetics system, we performed site-directed mutagenesis on loops I, II, III, and IV of TMUV E domain III. Mutant 6 (S388A.G389A.K390A) showed better proliferation than the wild-type virus, while mutants 1-5 exhibited decreased infectivity, as determined by immunofluorescence assay (IFA). Based on a TMUV replicon system, the mutations exhibited no apparent effect on TMUV RNA replication. Subcellular fractionation assays and packaging system assays indicated that mutations in loops II-IV (T332A, T332S, S365A.S366A.T367A, and S388A.G389A.K390A, respectively) disrupted virion assembly. Moreover, loops I-IV played an important role in virus binding and entry, while mutant 6 (S388A.G389A.K390A) exhibited robust activity in virus entry. Taken together, our findings indicated the critical role of the loop regions in TMUV E domain III in the virus entry and assembly process.
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http://dx.doi.org/10.3389/fmicb.2021.688172DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273266PMC
June 2021

Binding Features and Functions of ATG3.

Front Cell Dev Biol 2021 21;9:685625. Epub 2021 Jun 21.

School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.

Autophagy is an evolutionarily conserved catabolic process that is essential for maintaining cellular, tissue, and organismal homeostasis. Autophagy-related () genes are indispensable for autophagosome formation. is one of the key genes involved in autophagy, and its homologs are common in eukaryotes. During autophagy, ATG3 acts as an E2 ubiquitin-like conjugating enzyme in the ATG8 conjugation system, contributing to phagophore elongation. ATG3 has also been found to participate in many physiological and pathological processes in an autophagy-dependent manner, such as tumor occurrence and progression, ischemia-reperfusion injury, clearance of pathogens, and maintenance of organelle homeostasis. Intriguingly, a few studies have recently discovered the autophagy-independent functions of ATG3, including cell differentiation and mitosis. Here, we summarize the current knowledge of ATG3 in autophagosome formation, highlight its binding partners and binding sites, review its autophagy-dependent functions, and provide a brief introduction into its autophagy-independent functions.
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http://dx.doi.org/10.3389/fcell.2021.685625DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255673PMC
June 2021

The key amino acids of E protein involved in early flavivirus infection: viral entry.

Virol J 2021 07 3;18(1):136. Epub 2021 Jul 3.

Research Center of Avian Disease, College of Veterinary Medicine, Sichuan Agricultural University, Wenjiang District, Chengdu, 611130, Sichuan, China.

Flaviviruses are enveloped viruses that infect multiple hosts. Envelope proteins are the outermost proteins in the structure of flaviviruses and mediate viral infection. Studies indicate that flaviviruses mainly use envelope proteins to bind to cell attachment receptors and endocytic receptors for the entry step. Here, we present current findings regarding key envelope protein amino acids that participate in the flavivirus early infection process. Among these sites, most are located in special positions of the protein structure, such as the α-helix in the stem region and the hinge region between domains I and II, motifs that potentially affect the interaction between different domains. Some of these sites are located in positions involved in conformational changes in envelope proteins. In summary, we summarize and discuss the key envelope protein residues that affect the entry process of flaviviruses, including the process of their discovery and the mechanisms that affect early infection.
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http://dx.doi.org/10.1186/s12985-021-01611-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8254458PMC
July 2021

Evaluation of the Use of CT Attenuation for the Prediction of Subsequent Vertebral Fracture in Patients with Osteoporosis.

Pain Physician 2021 Jul;24(4):E493-E500

Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China.

Background: Subsequent vertebral fracture (SVF) is one of the most common complications of percutaneous vertebral augmentation (PVA), which leads to lower back pain in patients. Low bone mineral density (BMD) is an independent risk factor for SVF. BMD measured using computed tomography (CT) trabecular attenuation correlates closely with BMD.

Objectives: This study aims to analyze the risk factors of SVF after PVA and to estimate the predictive role of CT trabecular attenuation.

Study Design: A retrospective review.

Setting: Department of spinal surgery in an affiliated hospital of a medical university.

Methods: A total of 515 patients were retrospectively enrolled between January 2015 and December 2019 into a 5-year follow-up investigation. Trabecular attenuation (Hounsfield units [HU]) was retrospectively measured at L1 on preoperative lumbar or thoracic CT scans, and the receiver operating characteristic (ROC) curve was used to evaluate its value for the prediction of SVF. Kaplan-Meier analysis and Cox proportional hazards regression were performed to identify the risk factors for SVF.

Results: A total of 166 patients (32.2%) experienced SVF. ROC curve analysis demonstrated that an L1 trabecular attenuation of <= 95 HU has a sensitivity of 70.5% and a specificity of 79.9% for the prediction of SVF. Kaplan-Meier analysis showed that L1 trabecular attenuation <= 95 HU was significantly associated with lower SVF-free survival (P = 0.001; log-rank test). Multivariate analysis demonstrated that advanced age (hazard ratio [HR] = 1.03, P = 0.022), low body mass index (HR = 0.83, P = 0.001), diabetes status (HR = 1.50, P = 0.024), antiosteoporosis drugs use (HR = 0.65, P = 0.031), and decreased L1 trabecular attenuation (HR = 0.95, P = 0.001) were risk factors for SVF.

Limitations: A single-center retrospective study of a consecutive cohort of patients may include the inevitable bias. We periodically reviewed the full-length x-ray of the spine at every 3 months of follow-up visit, which we may miss some patients with SVF without low back pain.

Conclusions: SVF is highly prevalent in patients with osteoporotic vertebral fracture who undergo single-level PVA. Low L1 trabecular attenuation is associated with a significant reduction in SVF-free survival, and when their L1 trabecular attenuation is <= 95 HU, patients may be at higher risk of SVF.

Key Words: Computed tomography, Hounsfield units, vertebral fracture, osteoporosis, percutaneous vertebral augmentation.
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July 2021

Geographical Detector-Based Spatial Modeling of the COVID-19 Mortality Rate in the Continental United States.

Authors:
Han Yue Tao Hu

Int J Environ Res Public Health 2021 06 25;18(13). Epub 2021 Jun 25.

Department of Geography, Oklahoma State University, Stillwater, OK 74078, USA.

Investigating the spatial distribution patterns of disease and suspected determinants could help one to understand health risks. This study investigated the potential risk factors associated with COVID-19 mortality in the continental United States. We collected death cases of COVID-19 from 3108 counties from 23 January 2020 to 31 May 2020. Twelve variables, including demographic (the population density, percentage of 65 years and over, percentage of non-Hispanic White, percentage of Hispanic, percentage of non-Hispanic Black, and percentage of Asian individuals), air toxins (PM2.5), climate (precipitation, humidity, temperature), behavior and comorbidity (smoking rate, cardiovascular death rate) were gathered and considered as potential risk factors. Based on four geographical detectors (risk detector, factor detector, ecological detector, and interaction detector) provided by the novel Geographical Detector technique, we assessed the spatial risk patterns of COVID-19 mortality and identified the effects of these factors. This study found that population density and percentage of non-Hispanic Black individuals were the two most important factors responsible for the COVID-19 mortality rate. Additionally, the interactive effects between any pairs of factors were even more significant than their individual effects. Most existing research examined the roles of risk factors independently, as traditional models are usually unable to account for the interaction effects between different factors. Based on the Geographical Detector technique, this study's findings showed that causes of COVID-19 mortality were complex. The joint influence of two factors was more substantial than the effects of two separate factors. As the COVID-19 epidemic status is still severe, the results of this study are supposed to be beneficial for providing instructions and recommendations for the government on epidemic risk responses to COVID-19.
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http://dx.doi.org/10.3390/ijerph18136832DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8296863PMC
June 2021
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