Publications by authors named "Hang Fan"

86 Publications

Engineering high coenzyme Q tomato.

Metab Eng 2021 Sep 21;68:86-93. Epub 2021 Sep 21.

Shanghai Key Laboratory of Plant Functional Genomics and Resources, Plant Science Research Center, Shanghai Chenshan Botanical Garden, Shanghai, 201602, China. Electronic address:

Coenzyme Q (CoQ) is vital for energy metabolism in living organisms. In humans, CoQ deficiency causes diseases and must be replenished via diet; however, CoQ content in plant foods is primarily low. Here, we report the breeding of high CoQ tomato lines by expressing four enzymes with a fruit-specific promoter, which modifies the chloroplast chorismate pathway, enhances cytosolic isoprenoid biosynthesis, and up-regulates the first two reactions in mitochondrion that construct the CoQ polyisoprenoid tail. We show that, while the level of the aromatic precursor could be markedly elevated, head group prenylation is the key to increasing the final CoQ yield. In the HUCD lines expressing all four transgenes, the highest CoQ content (0.15 mg/g dry weight) shows a seven-fold increase from the wild-type level and reaches an extraordinarily rich CoQ food grade. Overviewing the changes in other terpenoids by transcriptome and metabolic analyses reveals variable contents of carotenoids and α-tocopherol in the HUCD lines. In addition to the enigmatic relations among different terpenoid pathways, high CoQ plants maintaining substantial levels of either vitamin can be selected. Our investigation paves the way for the development of CoQ-enriched crops as dietary supplements.
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http://dx.doi.org/10.1016/j.ymben.2021.09.007DOI Listing
September 2021

Difference of Intrahost Dynamics of the Second Human Pegivirus and Hepatitis C Virus in HPgV-2/HCV-Coinfected Patients.

Front Cell Infect Microbiol 2021 12;11:728415. Epub 2021 Aug 12.

Department of Epidemiology, School of Public Health, Southern Medical University, Guangzhou, China.

Background: The second human pegivirus (HPgV-2) and hepatitis C virus (HCV) belong to the Flaviviridae family and share some common genome features. However, the two viruses exhibit significantly different genetic diversity. The comparison of intrahost dynamics of HPgV-2 and HCV that mainly reflect virus-host interactions is needed to elucidate their intrahost difference of genetic diversity and the possible mechanisms.

Methods: Intrahost single nucleotide variations (iSNVs) were identified by means of next-generation sequencing from both cross-sectional and longitudinal samples from HPgV-2- and HCV-coinfected patients. The levels of human cytokines were quantified in the patient before and after HCV elimination by the treatment of direct-acting antivirals (DAA).

Results: Unlike HCV, the viral sequences of HPgV-2 are highly conserved among HPgV-2-infected patients. However, iSNV analysis confirmed the intrahost variation or quasispecies of HPgV-2. Almost all iSNVs of HPgV-2 did not accumulate or transmit within host over time, which may explain the highly conserved HPgV-2 consensus sequence. Intrahost variation of HPgV-2 mainly causes nucleotide transition in particular at the 3rd codon position and synonymous substitutions, indicating purifying or negative selection posed by host immune system. Cytokine data further indicate that HPgV-2 infection alone may not efficiently stimulate innate immune responses since proinflammatory cytokine expression dramatically decreased with elimination of HCV.

Conclusion: This study provided new insights into the intrahost genomic variations and evolutionary dynamics of HPgV-2 as well as the impact of host immune selection and virus polymerase on virus evolution. The different genetic diversity of HPgV-2 and HCV makes HPgV-2 a potential new model to investigate RNA virus diversity and the mechanism of viral polymerase in modulating virus replication.
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http://dx.doi.org/10.3389/fcimb.2021.728415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403064PMC
August 2021

Victimization and depressive symptoms among Chinese adolescents: A moderated mediation model.

J Affect Disord 2021 Nov 20;294:375-381. Epub 2021 Jul 20.

School of Humanities and Social Sciences, University of Science and Technology of China, No. 96 Jinzhai Road, Baohe District, Hefei 230022, PR China. Electronic address:

Background: Victimization as an inducing factor of depressive symptoms has been confirmed in previous studies. However, little is known about how and when it induces depressive symptoms in adolescents.

Methods: In total, 1174 Chinese adolescents were recruited to complete the Juvenile Victimization Questionnaire, Security Questionnaire, Positive Psychological Capital Questionnaire, and the Chinese version of the Center for Epidemiologic Studies Depression Scale.

Results: After controlling for gender and school type, the sense of security partially mediated the association between victimization and depressive symptoms. Moreover, direct association and the mediating effect of the sense of security were moderated by psychological capital. The moderating effect occurred in the second half of the mediating effect.

Limitations: Causal conclusions cannot be drawn based on cross-sectional research design. All measures were based on participant self-report.

Conclusions: The mediating model constructed in this study emphasized the important influence of stress, emotion, and psychological diathesis on adolescent depressive symptoms.
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http://dx.doi.org/10.1016/j.jad.2021.07.022DOI Listing
November 2021

Metatranscriptomic analysis identifies different viral-like sequences in two neotropical Mansoniini mosquito species.

Virus Res 2021 Aug 17;301:198455. Epub 2021 May 17.

Departamento de Entomologia, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Pernambuco, Brazil; Programa de Pós-graduação em Biociências e Biotecnologia em Saúde, Instituto Aggeu Magalhães, Fundação Oswaldo Cruz, Recife, Pernambuco, Brazil; Núcleo de Bioinformática, Fundação Oswaldo Cruz, Departamento de Entomologia, Recife, Pernambuco, Brazil. Electronic address:

Mosquitoes interact with a wide range of viruses including both arboviruses and insect-specific viruses. This study aimed to characterize the RNA viruses that are interacting with Mansonia wilsoni and Coquillettidia hermanoi mosquito species. The total RNA extracted from mosquito pools were sequenced on a Ion torrent platform. Viral contigs were identified against viral databases and their evolutionary relationship were reconstructed. We identified a total of 107 viral sequences, 11 of which were assigned as endogenous viral elements, and at least six known viral families were identified. Phylogenetic reconstructions were performed for 4 viral families. All Mansoniini viruses investigated through phylogenetic analysis are closely related to insect-specific viruses found in other mosquito species although with considerable divergence at the amino acid level, suggesting that we have detected new viral lineages. This study enhanced our understanding about the virome of two sylvatic Mansoniini mosquitoes.
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http://dx.doi.org/10.1016/j.virusres.2021.198455DOI Listing
August 2021

Convergent evolution of SARS-CoV-2 in human and animals.

Protein Cell 2021 Apr 30. Epub 2021 Apr 30.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, AMMS, Beijing, 100071, China.

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http://dx.doi.org/10.1007/s13238-021-00847-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085470PMC
April 2021

Clinical effect and antiviral mechanism of T-705 in treating severe fever with thrombocytopenia syndrome.

Signal Transduct Target Ther 2021 Apr 16;6(1):145. Epub 2021 Apr 16.

Department of Cancer, People's Liberation Army General Hospital, Beijing, P. R. China.

Severe fever with thrombocytopenia syndrome (SFTS) virus (SFTSV) is an emerging tick-borne virus with high fatality and an expanding endemic. Currently, effective anti-SFTSV intervention remains unavailable. Favipiravir (T-705) was recently reported to show in vitro and in animal model antiviral efficacy against SFTSV. Here, we conducted a single-blind, randomized controlled trial to assess the efficacy and safety of T-705 in treating SFTS (Chinese Clinical Trial Registry website, number ChiCTR1900023350). From May to August 2018, laboratory-confirmed SFTS patients were recruited from a designated hospital and randomly assigned to receive oral T-705 in combination with supportive care or supportive care only. Fatal outcome occurred in 9.5% (7/74) of T-705 treated patients and 18.3% (13/71) of controls (odds ratio, 0.466, 95% CI, 0.174-1.247). Cox regression showed a significant reduction in case fatality rate (CFR) with an adjusted hazard ratio of 0.366 (95% CI, 0.142-0.944). Among the low-viral load subgroup (RT-PCR cycle threshold ≥26), T-705 treatment significantly reduced CFR from 11.5 to 1.6% (P = 0.029), while no between-arm difference was observed in the high-viral load subgroup (RT-PCR cycle threshold <26). The T-705-treated group showed shorter viral clearance, lower incidence of hemorrhagic signs, and faster recovery of laboratory abnormities compared with the controls. The in vitro and animal experiments demonstrated that the antiviral efficacies of T-705 were proportionally induced by SFTSV mutation rates, particularly from two transition mutation types. The mutation analyses on T-705-treated serum samples disclosed a partially consistent mutagenesis pattern as those of the in vitro or animal experiments in reducing the SFTSV viral loads, further supporting the anti-SFTSV effect of T-705, especially for the low-viral loads.
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http://dx.doi.org/10.1038/s41392-021-00541-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050330PMC
April 2021

Classification of the Gut Microbiota of Patients in Intensive Care Units During Development of Sepsis and Septic Shock.

Genomics Proteomics Bioinformatics 2020 Dec 17;18(6):696-707. Epub 2021 Feb 17.

Department of Critical Care Medicine, Peking Union Medical College Hospital, Beijing 100730, China. Electronic address:

The gut microbiota of intensive care unit (ICU) patients displays extreme dysbiosis associated with increased susceptibility to organ failure, sepsis, and septic shock. However, such dysbiosis is difficult to characterize owing to the high dimensional complexity of the gut microbiota. We tested whether the concept of enterotype can be applied to the gut microbiota of ICU patients to describe the dysbiosis. We collected 131 fecal samples from 64 ICU patients diagnosed with sepsis or septic shock and performed 16S rRNA gene sequencing to dissect their gut microbiota compositions. During the development of sepsis or septic shock and during various medical treatments, the ICU patients always exhibited two dysbiotic microbiota patterns, or ICU-enterotypes, which could not be explained by host properties such as age, sex, and body mass index, or external stressors such as infection site and antibiotic use. ICU-enterotype I (ICU E1) comprised predominantly Bacteroides and an unclassified genus of Enterobacteriaceae, while ICU-enterotype II (ICU E2) comprised predominantly Enterococcus. Among more critically ill patients with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores > 18, septic shock was more likely to occur with ICU E1 (P = 0.041). Additionally, ICU E1 was correlated with high serum lactate levels (P = 0.007). Therefore, different patterns of dysbiosis were correlated with different clinical outcomes, suggesting that ICU-enterotypes should be diagnosed as independent clinical indices. Thus, the microbial-based human index classifier we propose is precise and effective for timely monitoring of ICU-enterotypes of individual patients. This work is a first step toward precision medicine for septic patients based on their gut microbiota profiles.
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http://dx.doi.org/10.1016/j.gpb.2020.06.011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8377022PMC
December 2020

Rapid, accurate, multifunctional and self-assisted vision assessment and screening with interactive desktop autostereoscopy.

Ann Transl Med 2021 Jan;9(1):23

State Key Laboratory of Optoelectronic Materials and Technology, School of Physics, Sun Yat-sen University, Guangzhou, China.

Background: This study aimed to develop an interactive vision screening tool based on desktop autostereoscopy and evaluate its feasibility for testing visual acuity, colour vision, stereo vision and binocular balance clinically.

Methods: An interactive desktop autostereoscopy vision test was developed making it remarkably convenient for individuals to undergo multiple visual function assessments in a single test. With this rapid screening process, an individual's visual acuity, colour vision, stereo vision and binocular balance can be assessed within several minutes. A total of 155 healthy subjects were enrolled to compare the clinical repeatability, accuracy, inter-visit variability, likeability and efficiency between the autostereoscopy and traditional method.

Results: In the repeatability test, the visual acuity measured with autostereoscopy was 0.045±0.018 and 0.035±0.018 (P=0.702) for the first and second tests, respectively. The mean logarithm of the Minimum Angle of Resolution (logMAR) visual acuities measured with the Early Treatment Diabetic Retinopathy Study (EDTRS) chart and autostereoscopy test were 0.04±0.02 and 0.05±0.02, respectively, which were not significantly different (P=0.849). The correlation between these two kinds of tests was statistically significant (Spearman correlation coefficient =0.829, P<0.001). The results for colour vision, stereo vision, and binocular vision are presented, and the effectiveness of the autostereoscopic method is supported with qualitative data comparing its results with those of the traditional methods. In the likeability test, the EDTRS chart and autostereoscopy test had scores of 2.21±0.53 and 3.04±0.07, while the traditional and autostereoscopy tests for colour vision, stereo vision, and binocular vision had scores of 2.02±0.59 and 3.36±0.93, respectively (P<0.001). Regarding visual fatigue, the mean scores were 0.69±0.04 and 0.42±0.04 (P<0.001) with the EDTRS chart and autostereoscopy test, respectively. Regarding work efficiency, the average testing times per person was 59.65±0.66 and 48.92±0.86 s (P<0.001) with the EDTRS chart and autostereoscopy test, respectively.

Conclusions: The autostereoscopy test was conclusively shown to be valid, efficient and repeatable for the measurement of visual acuity, colour vision, stereo vision, and binocular vision, and the process was subjectively well-liked and comfortable.
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http://dx.doi.org/10.21037/atm-20-3555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7859821PMC
January 2021

Liuzijue qigong versus traditional breathing training for patients with post-stroke dysarthria complicated by abnormal respiratory control: Results of a single-center randomized controlled trial.

Clin Rehabil 2021 Jul 1;35(7):999-1010. Epub 2021 Feb 1.

Department of Rehabilitation, Shanghai Shenyuan Rehabilitation Hospital, Shanghai, China.

Objective: The aim of the study was to investigate whether liuzijue qigong could improve the ability of respiratory control and comprehensive speech in patients with stroke dysarthria.

Design: A randomized controlled trial.

Setting: The research was carried out in the department of rehabilitation.

Participants: Altogether, a total of 98 stroke patients with dysarthria participated in the study.

Interventions: Patients were randomly divided into two groups (the experimental group: basic articulation + liuzijue qigong, 48 patients or the control group: basic articulation + traditional breathing training, 50 patients). All therapies were conducted once a day, five times a week for three weeks.

Main Measures: : Speech breathing level of the modified Frenchay Dysarthria Assessment. : the modified Frenchay Dysarthria Assessment, maximum phonation time, maximal counting ability, /s/, /z/, s/z ratio, and the loudness level. All outcome measures were assessed twice (at baseline and after three weeks).

Results: At three weeks, There were significant difference between the two groups in the change of speech breathing level (81% vs 66%,  = 0.011), the modified Frenchay Dysarthria Assessment (5.54 (4.68-6.40) vs 3.66 (2.92-4.40),  = 0.001), maximum phonation time (5.55 (4.92-6.18) vs 3.01(2.31-3.71),  < 0.01), maximal counting ability (3.08(2.45-3.71) vs 2.10 (1.53-2.67),  = 0.018), and /s/ (3.08 (2.39-3.78) vs 1.87 (1.23-2.51),  = 0.004), while no significant differences were found in the change of /z/ (3.08 (2.31-3.86) vs 2.10 (1.5-2.64),  = 0.08), / ratio (1.26 (0.96-1.55) vs 1.03 (0.97-1.09),  = 0.714), and the change of loudness level (69% vs 60%,  = 0.562).

Conclusions: Liuzijue qigong, combined with basic articulation training, could improve the respiratory control ability, as well as the comprehensive speech ability of stroke patients with dysarthria.

Trial Registration: ChiCTR-INR-16010215.
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http://dx.doi.org/10.1177/0269215521992473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193589PMC
July 2021

A narrative review of progress in diagnosis and treatment of small cell lung cancer patients with hyponatremia.

Transl Lung Cancer Res 2020 Dec;9(6):2469-2478

Department of Respiratory and Critical Care Medicine, Jinling Hospital, Southeast University of Medicine, Nanjing, China.

Small cell lung cancer (SCLC) is one of the malignant cancers of lung tumors, and hyponatremia, defined as serum sodium concentration (Na) lower than 135 mmol/L, is the most common complication of solid tumors, with an incidence of up to 18.9% and a negative impact on quality of life in SCLC. As a prognostic index of SCLC, timely monitoring and correcting of hyponatremia is of great clinical significance for prolonging the survival period of patients. In the explore of new drugs for small cell lung cancer, it is necessary to include hyponatremia as an evaluation index in clinical studies. As the occurrence of hyponatremia is sometimes unavoidable owing to SCLC specific neurological characteristics, early monitoring to detect the presence of hyponatremia and timely correction are helpful to improve the prognosis of patients. There are many predisposing factors for hyponatremia, including heterotopia of antidiuretic hormone (ADH), use of platinum-based chemotherapy drugs, and intracranial metastasis, among others. Patients with small cell lung cancer are usually asymptomatic in the early stage, while it is of great significance to find a suitable clinical index to judge whether it is a malignant inducement or not. In the clinical setting, due to different electrolyte levels and therapeutic scheduling for the primary disease, an individualized plan is often made, mainly comprising water restriction, infusion, and medications. This review includes related clinical studies and describes the common symptoms and predisposing factors of hyponatremia in patients with SCLC, and their impact on quality of life and prognosis.
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http://dx.doi.org/10.21037/tlcr-20-1147DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815354PMC
December 2020

The relationship between health-promoting lifestyles and depression in the elderly: roles of aging perceptions and social support.

Qual Life Res 2021 Mar 17;30(3):721-728. Epub 2020 Oct 17.

Department and Institute of Psychology, Ningbo University, No. 818 Fenghua Road, Jiangbei District, Ningbo, 315211, China.

Purpose: At present, it is not clear about the influence of health-promoting lifestyle, aging perceptions, social support, and other psychosocial factors on elderly depression. This study aims to explore the mediating role of aging perceptions between health-promoting lifestyle and elderly depression, and the moderating role of social support in the mediating process.

Methods: A cross-sectional survey was conducted among 359 elderly people in six districts of a city. The Chinese version of the Health-Promoting Lifestyle Profile-II (HPLP-IIR), the Brief Aging Perceptions Questionnaire (B-PQ), the Center for Epidemiological Studies Depression Scale (CES-DR), and the Social Support Rate Scale (SSRS) were conducted and recollected on the spot. Stepwise analysis was used to test the mediating effect and moderating effect, and age and gender variables were controlled.

Results: The results showed the following: (1) health-promoting lifestyle is an important influencing factor of elderly depression; (2) aging perceptions plays a mediating role in the relationship between health-promoting lifestyle and elderly depression, accounting for 31.8% of the total utility; and (3) social support plays a moderating role between aging perceptions and elderly depression, with a high level of social support. The effect of aging perceptions on depression is less than that of the elderly with low social support level.

Conclusion: Health-promoting lifestyle influence the depression of elderly people through aging perceptions and social support moderates the influence of aging perceptions on the elderly depression.
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http://dx.doi.org/10.1007/s11136-020-02674-4DOI Listing
March 2021

Biological characteristics and genome analysis of a novel phage vB_KpnP_IME279 infecting Klebsiella pneumoniae.

Folia Microbiol (Praha) 2020 Dec 16;65(6):925-936. Epub 2020 Oct 16.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.

Klebsiella pneumoniae (family Enterobacteriaceae) is a gram-negative bacterium that has strong pathogenicity to humans and can cause sepsis, pneumonia, and urinary tract infection. In recent years, the unreasonable use of antibacterial drugs has led to an increase in drug-resistant strains of K. pneumoniae, a serious threat to public health. Bacteriophages, viruses that infect bacteria, are ubiquitous in the natural environment. They are considered to be the most promising substitute for antibiotics because of their high specificity, high efficiency, high safety, low cost, and short development cycle. In this study, a novel phage designated vB_KpnP_IME279 was successfully isolated from hospital sewage using a multidrug-resistant strain of K. pneumoniae as an indicator. A one-step growth curve showed that vB_KpnP_IME279 has a burst size of 140 plaque-forming units/cell and a latent period of 20 min at its optimal multiplicity of infection (MOI = 0.1). Phage vB_KpnP_IME279 survives in a wide pH range between 3 and 11 and is stable at temperatures ranging from 40 to 60 °C. Ten of the 20 strains of K. pneumoniae including the host bacteria were lysed by the phage vB_KpnP_IME279, and the multilocus sequence typing and wzi typing of the 10 strains were ST11, ST37, ST375, wzi209, wzi52, and wzi72, respectively. The genome of vB_KpnP_IME279 is 42,518 bp long with a G + C content of 59.3%. Electron microscopic observation showed that the phage belongs to the family Podoviridae. BLASTN alignment showed that the genome of the phage has low similarity with currently known phages. The evolutionary relationship between phage vB_KpnP_IME279 and other Podoviridae was analyzed using a phylogenetic tree based on sequences of phage major capsid protein and indicates that the phage vB_KpnP_IME279 belongs to the Podoviridae subfamily. These data enhance understanding of K. pneumoniae phages and will help in development of treatments for multidrug-resistant bacteria using phages.
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http://dx.doi.org/10.1007/s12223-020-00775-8DOI Listing
December 2020

A glance at the gut microbiota of five experimental animal species through fecal samples.

Sci Rep 2020 10 6;10(1):16628. Epub 2020 Oct 6.

Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences, Beijing, China.

Experimental animals including the ferret, marmoset, woodchuck, mini pig, and tree shrew have been used in biomedical research. However, their gut microbiota have not been fully investigated. In this study, the gut microbiota of these five experimental animals were analyzed with 16S rRNA sequencing. The phyla Firmicutes, Bacteroidetes, and Fusobacteria were present in the gut microbiota of all the species. Specific phyla were present in different animals: Proteobacteria in the ferret, Tenericutes in the marmoset, and Spirochaetes in the mini pig. Fusobacterium and unidentified Clostridiales were the dominant genera in the ferret, whereas Libanicoccus, Lactobacillus, Porphyromonas, and Peptoclostridium were specific to marmoset, mini pig, woodchuck, and tree shrew, respectively. A clustering analysis showed that the overall distribution of microbial species in the guts of these species mirrored their mammalian phylogeny, and the microbiota of the marmoset and tree shrew showed the closest bray_curtis distances to that of humans. PICRUSt functional prediction separated the woodchuck from the other species, which may reflect its herbivorous diet. In conclusion, both the evolutionary phylogeny and daily diet affect the gut microbiota of these experimental animals, which should not be neglected for their usage in biomedical research.
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http://dx.doi.org/10.1038/s41598-020-73985-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538948PMC
October 2020

Identification of a Novel Phage-Derived Depolymerase and Its Therapeutic Application in Mice.

Front Microbiol 2020 21;11:1407. Epub 2020 Jul 21.

Department of Respiratory and Critical Care Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China.

The rapid expansion of clinical isolates exhibiting resistance to most or all available antibiotics is a global concern. Current treatments for infections caused by this bacterium have become less effective, and the need to explore new alternative therapies is urgent. Depolymerases derived from phages are emerging as attractive anti-virulence agents. In this study, a previously isolated phage (designated as vB_AbaM_IME285) was characterized, and genomic study was carried out using various bioinformatics tools. A gene predicted as encoding for the depolymerase was cloned and expressed, and the depolymerase activity of the recombinant enzyme (Dp49) was identified both and in experimental mice. The results showed that phage IME285 formed translucent halos around the plaques when inoculated onto a lawn of the host bacteria, exibiting depolymerase activity against this strain. On the basis of complete genome sequencing and bioinformatics analysis, ORF49 was speculated to be a gene encoding for the putative capsule depolymerase. The expressed recombinant Dp49 displayed an effective depolymerase activity and had a spectrum of activity similar to its parental phage IME285, which was active against 25 out of 49 strains. It was found that Dp49 greatly improved the inhibitory effect of serum on bacterial growth , and the administration of this enzyme significantly increased the survival rates of -infected mice in the animal experiment. In conclusion, the phage-encoded depolymerase Dp49 might be a promising alternative means of controlling infections mediated by multidrug-resistant .
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http://dx.doi.org/10.3389/fmicb.2020.01407DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7396526PMC
July 2020

Comparative Effect of Liuzijue Qigong and Conventional Respiratory Training on Trunk Control Ability and Respiratory Muscle Function in Patients at an Early Recovery Stage From Stroke: A Randomized Controlled Trial.

Arch Phys Med Rehabil 2021 03 12;102(3):423-430. Epub 2020 Aug 12.

Department of Rehabilitation, Shanghai Xuhui Central Hospital, Shanghai, China.

Objectives: To compare the effects of Liuzijue Qigong and conventional respiratory training on trunk control ability and respiratory muscle functions in patients at an early recovery stage from stroke.

Design: A single-blind, randomized controlled trial.

Setting: A hospital.

Participants: Patients (N=60) within 2 months poststroke.

Interventions: The experimental group (n=30) received conventional rehabilitation training combined with Liuzijue exercise, and the control group (n=30) received conventional rehabilitation training combined with conventional respiration training. The training in the 2 groups was conducted 5 times per week for 3 weeks.

Main Outcome Measures: Trunk Impairment Scale (TIS), maximum inspiratory pressure (MIP), maximum expiratory pressure (MEP), forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), peak expiratory flow (PEF), maximum expiratory mid-flow (MMEF), diaphragmatic movement, the change of intra-abdominal pressure (IAP), Berg Balance Scale (BBS), and Modified Barthel Index (MBI). All outcome measures were assessed twice (at baseline and 3 weeks).

Results: Both groups significantly improved in TIS, MIP, FVC, PEF, and the change of IAP, BBS, and MBI when pre- and postassessments (P<.05) were compared. Compared with the control group, there was a significant difference in the experimental group in the static sitting balance subscale (P=.014), dynamic balance subscale (P=.001), coordination subscale (P<.001), TIS total scores (P<.001; effect size [ES]=0.9), MIP (P=.012; 95% confidence interval [CI], 2.23-17.69; ES=0.67), MEP (P=.015; 95% CI, 1.85-16.57; ES=0.65), change of IAP (P=.001), and MBI (P=.016; 95% CI, 1.51-14.16; ES=0.64). No significant differences were found between the 2 groups in FEV1 (P=.24), FVC (P=.43), PEF (P=.202), MMEF (P=.277), the diaphragmatic movement of quiet breathing (P=.146), deep breathing (P=.102), and BBS (P=.124).

Conclusions: Liuzijue exercise showed more changes than conventional respiratory training in improving trunk control ability, respiratory muscle functions, and activities of daily living ability in patients at an early recovery stage from stroke.
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http://dx.doi.org/10.1016/j.apmr.2020.07.007DOI Listing
March 2021

A Thermostable mRNA Vaccine against COVID-19.

Cell 2020 09 23;182(5):1271-1283.e16. Epub 2020 Jul 23.

Suzhou Abogen Biosciences Co., Ltd., Suzhou 215123, China. Electronic address:

There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.
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http://dx.doi.org/10.1016/j.cell.2020.07.024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377714PMC
September 2020

Adaptation of SARS-CoV-2 in BALB/c mice for testing vaccine efficacy.

Science 2020 09 30;369(6511):1603-1607. Epub 2020 Jul 30.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, China.

The ongoing coronavirus disease 2019 (COVID-19) pandemic has prioritized the development of small-animal models for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We adapted a clinical isolate of SARS-CoV-2 by serial passaging in the respiratory tract of aged BALB/c mice. The resulting mouse-adapted strain at passage 6 (called MASCp6) showed increased infectivity in mouse lung and led to interstitial pneumonia and inflammatory responses in both young and aged mice after intranasal inoculation. Deep sequencing revealed a panel of adaptive mutations potentially associated with the increased virulence. In particular, the N501Y mutation is located at the receptor binding domain (RBD) of the spike protein. The protective efficacy of a recombinant RBD vaccine candidate was validated by using this model. Thus, this mouse-adapted strain and associated challenge model should be of value in evaluating vaccines and antivirals against SARS-CoV-2.
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http://dx.doi.org/10.1126/science.abc4730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574913PMC
September 2020

Identification and Molecular Characterization of a New Omono River Virus Isolated from Culex Tritaeniorhynchus in Yunnan, China.

Virol Sin 2021 Feb 20;36(1):152-154. Epub 2020 Jul 20.

Beijing Advanced Innovation Center for Soft Matter Science and Engineering (BAIC-SM), College of Life Science and Technology, Beijing University of Chemical Technology, Beijing, 100029, China.

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http://dx.doi.org/10.1007/s12250-020-00247-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7973334PMC
February 2021

Distribution and characteristics of Beilong virus among wild rodents and shrews in China.

Infect Genet Evol 2020 11 4;85:104454. Epub 2020 Jul 4.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, PR China; Beijing Key Laboratory of Vector Borne and Natural Focus Infectious Diseases, Beijing, PR China. Electronic address:

Beilong virus (BeiV), a member of the newly recognized genus Jeilongvirus of family Paramyxoviridae, has been reported with limited geographic and host scopes, only in Hongkong, China and from two rat species. Here, by next-generation sequencing (NGS) on dominant wild small animal species in 4 provinces in China, we obtained a complete sequence of BeiV strain from Rattus norvegicus in Guangdong, neighboring HongKong, China. We then made an expanded epidemiological investigation in 11 provinces to obtain the geographic distribution and genetic features of this virus. Altogether 7168 samples from 2005 animals (1903 rodents, 100 shrews, 2 mustelidaes) that belonged to 33 species of Cricetidae, Muridae, Sciuridae and Dipodidae family of Rodentia, 3 species of Soricidae family of Soricomorpha, 2 species of Mustelidae family of Carnivora were examined by RT-PCR and sequencing. A positive rate of 3.7% (266/7168) was obtained that was detected from 22 animal species, including 5 species of Cricetidae family, 12 species of Muridae family, 2 species of Sciuridae family and 3 species of Soricidae family. Phylogenetic analyses based on 154 partial Large gene sequences grouped the current BeiV into two lineages, that were related to their geographic regions and animal hosts. Our study showed the wide distribution of BeiV in common species of wild rodents and shrews in China, highlighting the necessity of epidemiological study in wider regions.
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http://dx.doi.org/10.1016/j.meegid.2020.104454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335238PMC
November 2020

Complete genome sequence of a novel bovine hepacivirus from Yunnan, China.

Arch Virol 2020 Jun 7;165(6):1489-1494. Epub 2020 Apr 7.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, People's Republic of China.

We detected a novel bovine hepacivirus N (HNV) subtype, IME_BovHep_01, in the serum of cattle in Tengchong, Yunnan, China, by high-throughput sequencing. The complete genome of IME_BovHep_01, was sequenced using an Illumina MiSeq sequencer and found to be 8850 nt in length, encoding one hypothetical protein. BLASTn analysis showed that the genome sequence shared similarity with the bovine hepacivirus isolate BovHepV_209/Ger/2014, with 88% query coverage and 70.8% identity. However, the highest similarity was to bovine hepacivirus N strain BRBovHep_RS963, for which only a partial genome sequence is available, with 68% query coverage and 81.5% identity. Sequence comparisons and phylogenetic analysis suggested that IME_BovHep_01 is a novel HNV subtype. Importantly, IME_BovHep_01 is the first member of this new genotype for which the complete genome sequence was determined.
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http://dx.doi.org/10.1007/s00705-020-04611-9DOI Listing
June 2020

Importing coronavirus disease 2019 (COVID-19) into China after international air travel.

Travel Med Infect Dis 2020 May - Jun;35:101620. Epub 2020 Mar 25.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 100071, Beijing, PR China. Electronic address:

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http://dx.doi.org/10.1016/j.tmaid.2020.101620DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102655PMC
July 2020

Virome diversity analysis reveals novel enteroviruses and a human picobirnavirus in stool samples from African green monkeys with diarrhea.

Infect Genet Evol 2020 08 10;82:104279. Epub 2020 Mar 10.

Chinese PLA Medical School, Beijing 100853, China; Fifth Medical Center of Chinese PLA General Hospital, Beijing 100039, China. Electronic address:

It is important to identify viruses in animals because most infectious diseases in humans are caused by viruses of zoonotic origin. African green monkey is a widely used non-human primate model in biomedical investigations. In this study, total RNAs were extracted from stool samples of 10 African green monkeys with diarrhea. High-throughput sequencing was used to characterize viromes. PCR and Sanger sequencing were used to determine the full genome sequences. Great viral diversity was observed. The dominant viruses were enteroviruses and picobirnaviruses. Six enterovirus genomes and a picobirnavirus RNA-dependent RNA polymerase sequence were characterized. Five enteroviruses belonged to two putative new genotypes of species Enterovirus J. One enterovirus belonged to EV-A92. The picobirnavirus RNA-dependent RNA polymerase sequence had the highest nucleotide similarity (93.48%) with human picobirnavirus isolate GPBV6C2. The present study helped to identify the potential zoonotic viruses in African green monkeys. Further investigations are required to elucidate their pathogenic roles in animals and humans.
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http://dx.doi.org/10.1016/j.meegid.2020.104279DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7102571PMC
August 2020

Characteristics and complete genome sequence of the virulent Vibrio alginolyticus phage VAP7, isolated in Hainan, China.

Arch Virol 2020 Apr 4;165(4):947-953. Epub 2020 Mar 4.

Department of Graduate, Hebei North University, Zhangjiakou, 075000, China.

A novel Vibrio alginolyticus phage, VAP7, was isolated from seawater collected from Sanya, Hainan province, China. Whole-genome sequencing analysis revealed that phage VAP7 has a linear, double-stranded DNA genome of 144,685 bp with an average G+C content of 41.9% and a high degree of sequence similarity to Vibrio phage VP-1. Annotation results identified 193 open reading frames and one transfer RNA-encoding gene in the phage genome. The morphology and the results of phylogenetic analysis suggest that VAP7 should be classified as a new member of the family Ackermannviridae. Moreover, phage VAP7 grew over a wide pH (5.0-10.0) and temperature (4-40 °C) range. Host-range experiments revealed that VAP7 could infect 31 Vibrio alginolyticus strains. Thus, VAP7 infecting Vibrio alginolyticus strains represents a potential new candidate for use in phage therapy.
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http://dx.doi.org/10.1007/s00705-020-04535-4DOI Listing
April 2020

High prevalence and viremia of human pegivirus 2 in the HIV-infected population in Honghe Prefecture, Yunnan Province.

Arch Virol 2020 Mar 21;165(3):619-626. Epub 2020 Jan 21.

Department of AIDS Research, State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, 20 Dongda Street, Fengtai District, Beijing, 100071, China.

Human pegivirus 2 (HPgV-2) is a recently recognized pegivirus of the family Flaviviridae. To investigate the epidemic features of HPgV-2 circulating in the human immunodeficiency virus (HIV)-infected population, we tested for antibodies and viral RNA of HPgV-2 and hepatitis C virus (HCV) with retrospective plasma samples collected from 771 HIV infections with multiple risk behaviors in Honghe Prefecture of Yunnan Province. A total of 195 subjects (25.29%) were seroreactive to HPgV-2, and 41 (5.32%) were RNA positive. Although the positive rate of HPgV-2 antibodies in HIV/HCV-coinfected individuals (27.69%) was significantly higher than that of HIV monoinfections (20.82%) (p = 0.036), this is the first report of HPgV-2 viremia in HIV-infected individuals without HCV infection and the presence of two HPgV-2 lineages in China. Our data indicate that HPgV-2 can also be transmitted sexually, which might be facilitated when combined with HCV infection, injecting drug use, and risky sexual behavior, which appear to have a synergistic effect on HPgV-2 infection. Phylogenetic analysis of 26 near-full-length genome sequences showed that the HPgV-2 strains in China are divided into two clusters.
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http://dx.doi.org/10.1007/s00705-019-04512-6DOI Listing
March 2020

Impacts of Physical and Biological Processes on Spatial and Temporal Variability of Particulate Organic Carbon in the North Pacific Ocean during 2003-2017.

Sci Rep 2019 11 11;9(1):16493. Epub 2019 Nov 11.

Institute of Oceanology, Chinese Academy of Sciences, Qingdao, 266071, Shandong, China.

The North Pacific Ocean is a significant carbon sink region, but little is known about the dynamics of particulate organic carbon (POC) and the influences of physical and biological processes in this region at the basin scale. Here, we analysed high-resolution surface POC data derived from MODIS-Aqua during 2003-2017, together with satellite-derived sea surface chlorophyll and temperature (SST). There are large spatial and temporal variations in surface POC in the North Pacific. Surface POC is much lower in the subtropical region (<50 mg m) than in the subarctic region (>100 mg m), primarily resulting from the south-to-north variability in biological production. Our analyses show significant seasonal and interannual variability in surface POC. In particular, there is one peak in winter-spring in the western subtropical region and two peaks in late spring and fall in the western subarctic region. Surface POC is positively correlated with chlorophyll (r = ~1) and negatively correlated with SST (r = ~-0.45, P < 0.001) south of 45°N, indicating the strong influence of physically driven biological activity on the temporal variability of POC in the subtropical region. There is a significantly positive but relatively lower correlation coefficient (0.6-0.8) between POC and chlorophyll and an overall non-significantly positive correlation between POC and SST north of 45°N, reflecting the reduction in the POC standing stock due to the fast sinking of large particles. The climate modes of the Pacific Decadal Oscillation, El Niño-Southern Oscillation and North Pacific Gyre Oscillation have large impacts on POC in various seasons in the subtropical region and weak influences in the subarctic region. Surface POC was anomalously high after 2013 (increased by ~15%) across the basin, which might be the result of complex interactions of physical and biological processes associated with an anomalous warming event (the Blob).
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http://dx.doi.org/10.1038/s41598-019-53025-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6848136PMC
November 2019

WNT5B exerts oncogenic effects and is negatively regulated by miR-5587-3p in lung adenocarcinoma progression.

Oncogene 2020 02 30;39(7):1484-1497. Epub 2019 Oct 30.

Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine, Nanjing, 210002, Jiangsu, China.

WNT5B glycoprotein belongs to the Wnt protein family. Limited investigations revealed a possible role of WNT5B in malignancies, such as triple-negative breast cancer and oral squamous cell carcinoma. However, whether WNT5B contributes to the progression of lung adenocarcinoma (LAD) remains unclear. Here, we initially determine that WNT5B is highly expressed in LAD and is positively correlated with lymph node metastasis and TNM stage. Consistently, clinical analysis reveals WNT5B as an independent prognostic biomarker in LAD. Silencing WNT5B suppresses the proliferation of LAD both in vitro and in vivo by interfering G1/S cell-cycle progression and modulating amino acid metabolism, revealing its remarkable oncogenic role in LAD. Of note, we also identified miR-5587-3p as a negative upstream regulator of WNT5B in LAD, which may help develop therapies targeting LAD patients with high WNT5B expression. Taken together, our results revealed an oncogenic role of WNT5B in LAD, which could be a prognostic biomarker and promising therapeutic target for LAD patients.
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http://dx.doi.org/10.1038/s41388-019-1071-4DOI Listing
February 2020

Genetic diversity, virulence factors and farm-to-table spread pattern of Vibrio parahaemolyticus food-associated isolates.

Food Microbiol 2019 Dec 13;84:103270. Epub 2019 Jul 13.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China. Electronic address:

Vibrio parahaemolyticus is the leading bacterial cause of seafood-associated gastroenteritis worldwide. Moreover, infections and outbreaks caused by V. parahaemolyticus has kept increasing over the last two decades. In this study, we investigated the genetic diversity, virulence factors and farm-to-table spread pattern of V. parahaemolyticus by analyzing 383 genomes of food-associated isolates. These strains were isolated from diverse sample types from six provinces of China in 2014, being classified into three tiers of the farm-to-table spread process: food production, circulation and consumption. The genetic diversity of V. parahaemolyticus in different classifications, including geographical location, sample type, source and spread tier, was similar, as the median number of pairwise SNPs within each classification was between 33,013 and 33,659. Specifically, there was no clear boundaries in genetic diversity of the isolates from inland vs. coastal provinces, as well as of those from freshwater vs. seawater products. Moreover, the virulence genes and genomic islands were only found in a small number of isolates, indicating a low disease risk of the food-associated isolates in this study. By further exploring 28 recently emerged clonal groups, we identified seven farm-to-table spread events, showing a common pattern of single-source radial spread accompanied with occasional gene gain/loss events. Generally speaking, our work highlighted the colonization of V. parahaemolyticus in inland provinces and freshwater environment, and provided a snapshot of the farm-to-table spread pattern of V. parahaemolyticus food-associated isolates. Our results showed the feasibility of tracking the farm-to-table spread of foodborne pathogen, which would help construct the whole genome sequencing-based molecular tracking network in the future.
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http://dx.doi.org/10.1016/j.fm.2019.103270DOI Listing
December 2019

Effect of Parent-Child Attachment on College Students' Social Anxiety: A Moderated Mediation Model.

Psychol Rep 2020 Dec 23;123(6):2196-2214. Epub 2019 Jul 23.

Department and Institute of Psychology, 47862Ningbo University, Ningbo, China.

This study investigated the relationship between parent-child attachment and social anxiety in college students, as well as the mediating role of psychological resilience and the moderating role of online social support. In total, 614 college students were recruited by the cluster sampling method. The results showed that (1) parent-child attachment was negatively correlated with college students' social anxiety and positively correlated with their psychological resilience, (2) psychological resilience played a mediating role between parent-child attachment and college students' social anxiety, and (3) online social support regulated the first half and second half of the mediation process in which parent-child attachment affected college students' social anxiety through psychological resilience. These findings revealed the mechanism of parent-child attachment affecting social anxiety, which had important theoretical and empirical value for enhancing the strength of college students' psychological resilience and alleviating social anxiety.
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http://dx.doi.org/10.1177/0033294119862981DOI Listing
December 2020

Characterization and complete genome sequence analysis of phage GP4, a novel lytic Bcep22-like podovirus.

Arch Virol 2019 Sep 18;164(9):2339-2343. Epub 2019 Jun 18.

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, 100071, China.

We isolated a novel lytic phage of Ralstonia solanacearum, GP4. The GP4 phage has a latent period of ~ 2 h at its optimal multiplicity of infection and is stable at temperatures ranging from 40-70 °C. GP4 lysed 16 strains of R. solanacearum belonging to phylotype IV. High-throughput sequencing revealed that GP4 has a linear dsDNA genome that consists of 61,129 bp, contains 83 open reading frames, and encodes a tRNA for cysteine. The GP4 genome has low similarity to other phage sequences in the GenBank database. Phylogenetic analysis indicated that GP4 can be taxonomically classified as a member of the Bcep22-like subfamily of the family Podoviridae.
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http://dx.doi.org/10.1007/s00705-019-04309-7DOI Listing
September 2019
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