Publications by authors named "Yanxia Wang"

181 Publications

Safety and immunogenicity of an inactivated COVID-19 vaccine, BBIBP-CorV, in people younger than 18 years: a randomised, double-blind, controlled, phase 1/2 trial.

Lancet Infect Dis 2021 Sep 15. Epub 2021 Sep 15.

Beijing Institute of Biological Products, Beijing, China.

Background: Although SARS-CoV-2 infection often causes milder symptoms in children and adolescents, young people might still play a key part in SARS-CoV-2 transmission. An efficacious vaccine for children and adolescents could therefore assist pandemic control. For further evaluation of the inactivated COVID-19 vaccine candidate BBIBP-CorV, we assessed the safety and immunogenicity of BBIBP-CorV in participants aged 3-17 years.

Methods: A randomised, double-blind, controlled, phase 1/2 trial was done at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan, China. In phases 1 and 2, healthy participants were stratified according to age (3-5 years, 6-12 years, or 13-17 years) and dose group. Individuals with a history of SARS-CoV-2 or SARS-CoV infection were excluded. All participants were randomly assigned, using stratified block randomisation (block size eight), to receive three doses of 2 μg, 4 μg, or 8 μg of vaccine or control (1:1:1:1) 28 days apart. The primary outcome, safety, was analysed in the safety set, which consisted of participants who had received at least one vaccination after being randomly assigned, and had any safety evaluation information. The secondary outcomes were geometric meant titre (GMT) of the neutralising antibody against infectious SARS-CoV-2 and were analysed based on the full analysis set. This study is registered with www.chictr.org.cn, ChiCTR2000032459, and is ongoing.

Findings: Between Aug 14, 2020, and Sept 24, 2020, 445 participants were screened, and 288 eligible participants were randomly assigned to vaccine (n=216, 24 for each dose level [2/4/8 μg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=72, 24 for each age cohort [3-5, 6-12, and 13-17 years]) in phase 1. In phase 2, 810 participants were screened and 720 eligible participants were randomly assigned and allocated to vaccine (n=540, 60 for each dose level [2/4/8 μg] in each of three age cohorts [3-5, 6-12, and 13-17 years]) or control (n=180, 60 for each age cohort [3-5, 6-12, and 13-17 years]). The most common injection site adverse reaction was pain (ten [4%] 251 participants in all vaccination groups of the 3-5 years cohort; 23 [9·1%] of 252 participants in all vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 20 [7·9%] of 252 participants in all vaccination groups of the 13-17 years cohort). The most common systematic adverse reaction was fever (32 [12·7%] of 251 participants in all vaccination groups and six [7·1%] of 84 participants in the control group of the 3-5 years cohort; 13 [5·2%] of 252 participants in the vaccination groups and one [1·2%] of 84 in the control group of the 6-12 years cohort; 26 [10·3%] of 252 participants in all vaccination groups and eight [9·5%] of 84 in the control group of the 13-17 years cohort). Adverse reactions were mostly mild to moderate in severity. The neutralising antibody GMT against the SARS-CoV-2 virus ranged from 105·3 to 180·2 in the 3-5 years cohort, 84·1 to 168·6 in the 6-12 years cohort, and 88·0 to 155·7 in the 13-17 years cohort on day 28 after the second vaccination; and ranged from 143·5 to 224·4 in the 3-5 years cohort, 127 to 184·8 in the 6-12 years cohort, and 150·7 to 199 in the 13-17 years cohort on day 28 after the third vaccination.

Interpretation: The inactivated COVID-19 vaccine BBIBP-CorV is safe and well tolerated at all tested dose levels in participants aged 3-17 years. BBIBP-CorV also elicited robust humoral responses against SARS-CoV-2 infection after two doses. Our findings support the use of a 4 μg dose and two-shot regimen BBIBP-CorV in phase 3 trials in the population younger than 18 years to further ascertain its safety and protection efficacy against COVID-19.

Funding: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan.

Translation: For the Chinese translation of the abstract see Supplementary Materials section.
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http://dx.doi.org/10.1016/S1473-3099(21)00462-XDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8443232PMC
September 2021

[Study on the structural changes of pharyngeal cavity after bariatric surgery in obese patients with obstructive sleep apnea].

Lin Chung Er Bi Yan Hou Tou Jing Wai Ke Za Zhi 2021 Jun;35(6):538-542

Department of Otorhinolaryngology,the Second Hospital of Hebei Medical University,Shijiazhuang,050000,China.

To study whether and how bariatric surgery changes the structure of the pharyngeal cavity in obese patients with obstructive sleep apnea(OSA). Forty-two patients who underwent laparoscopic sleeve gastrectomy were recruited. Morphological indicators(BMI, neck and waist circumference), PSG and acoustic pharyngometry indicators were evaluated pre-operatively and 3, 6, and 12 months post-operatively. All indicators including morphology, pharyngeal cavity structure and OSA severity changed significantly after surgery. Among them, BMI, neck circumference, waist circumference and AHI value were significantly reduced(<0.001), while pharyngeal cavity volume, pharynx volume, oropharyngeal junction area, glottis area and LSaO2 increased significantly(<0.001). The results of multiple comparisons showed that BMI, neck and waist circumference decreased significantly in the first 6 months, and no further decline occurred during 6 to 12 months postoperatively. The decrease in AHI and LSaO2 mainly occurred within the first 3 months postoperatively, while there was no statistically significant difference in these two indicatiors between 3 months vs. 6 months, 6 months vs. 12 months postoperatively. The area of the oropharyngeal junction increased significantly within 0 to 3 months after surgery, while the volume of the pharyngeal cavity and the area of the glottis increased at 6 months and 12 months after surgery. Bariatric surgery can significantly reduce body weight and reduce fat accumulation in the neck. It can also enlarge the volume and cross-sectional area of the pharyngeal cavity, and improve upper airway obstruction, therefore reduce the symptoms of sleep apnea in obese patients with OSA to a certain extent.
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http://dx.doi.org/10.13201/j.issn.2096-7993.2021.06.012DOI Listing
June 2021

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine in healthy adults aged 18 years or older: A randomized, double-blind, placebo-controlled, phase 1/2 trial.

EClinicalMedicine 2021 Aug 7;38:101010. Epub 2021 Jul 7.

National Engineering Technology Research Centre for Combined Vaccines, Wuhan Institute of Biological Products Co. Ltd., Wuhan, Hubei, China.

Background: We aimed to assess the safety and immunogenicity of an inactivated vaccine against COVID-19 in Chinese adults aged ≥18 years.

Methods: This is an ongoing randomized, double-blind, placebo-controlled, phase 1/2 clinical trial among healthy adults aged ≥18 years in Henan Province, China. Participants ( = 336 in 18-59 age group and  = 336 in ≥60 age group) were enrolled between April 12 and May 17 2020, and were equally randomized to receive vaccine or placebo (aluminum hydroxide adjuvant) in a three-dose schedule of 2·5, 5, or 10 µg on days 0, 28, and 56. Another 448 adults aged 18-59 years were equally allocated to four groups (a one-dose schedule of 10 µg, and two-dose schedules of 5 µg on days 0 and 14/21/28) and received vaccine or placebo (ratio 3:1 within each group). The primary outcomes were 7-day post-injection adverse reactions and neutralizing antibody titres on days 28 and 90 after the whole-course vaccination. Trial registration: www.chictr.org.cn #ChiCTR2000031809.

Findings: The 7-day adverse reactions occurred in 4·8% to 32·1% of the participants in various groups, and most adverse reactions were mild, transient, and self-limiting. Twenty participants reported 68 serious adverse events which were judged to be unrelated to the vaccine. The 90-day post-injection geometric mean titres of neutralizing antibody ranged between 87 (95% CI: 61-125) and 129 (99-169) for three-dose schedule among younger and older adults; 20 (14-27), 53 (38-75), and 44 (32-61) in 5 µg days 0 and 14/21/28 groups, respectively, and 7 (6-9) in one-dose 10 µg group. There were no detectable antibody responses in all placebo groups.

Interpretation: The inactivated vaccine against COVID-19 was well tolerated and immunogenic in both younger and older adults. The two-dose schedule of 5 µg on days 0 and 21/28 and three-dose schedules on days 0, 28, and 56 could be further evaluated for long-term safety and efficacy in the phase 3 trials.
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http://dx.doi.org/10.1016/j.eclinm.2021.101010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8260504PMC
August 2021

Ferromagnetic Dirac half-metallicity in transition metal embedded honeycomb borophene.

Phys Chem Chem Phys 2021 Aug 29;23(32):17150-17157. Epub 2021 Jun 29.

Key Laboratory of Material Modification by Laser, Ion and Electron Beams, Dalian University of Technology, Ministry of Education, Dalian 116024, China.

Exploring two-dimensional (2D) ferromagnetic materials with intrinsic Dirac half-metallicity is crucial for the development of next-generation spintronic devices. Based on first-principles calculations, here we propose a simple valence electron-counting rule to design such materials and endow them with good stability and desirable magnetic properties. Taking honeycomb borophene as a prototype, we demonstrate that embedding open-shell transition metal (like Cr) atoms in the hexagonal ring of boron atoms can provide two valence electrons to fully occupy the in-plane σ and out-of-plane π bands of B atoms. The remaining four valence electrons reside in d orbitals that split under C symmetry, yielding a magnetic moment of ∼2 μ per Cr atom. The resulting CrB monolayer exhibits a Dirac half-metal band structure, a high Curie temperature of 175 K, and a large out-of-plane magnetic anisotropy energy of 4 meV per Cr simultaneously. Our work establishes a feasible route for the experimental realization of ferromagnetic Dirac half-metallicity in 2D materials and provides new opportunity to realize high-speed devices with low consumption.
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http://dx.doi.org/10.1039/d1cp01708jDOI Listing
August 2021

Asymmetric Somatic Hybridization Affects Synonymous Codon Usage Bias in Wheat.

Front Genet 2021 11;12:682324. Epub 2021 Jun 11.

The Key Laboratory of Plant Development and Environmental Adaption, Ministry of Education, School of Life Science, Shandong University, Jinan, China.

Asymmetric somatic hybridization is an efficient strategy for crop breeding by introducing exogenous chromatin fragments, which leads to whole genomic shock and local chromosomal shock that induces genome-wide genetic variation including indel (insertion and deletion) and nucleotide substitution. Nucleotide substitution causes synonymous codon usage bias (SCUB), an indicator of genomic mutation and natural selection. However, how asymmetric somatic hybridization affects SCUB has not been addressed. Here, we explored this issue by comparing expressed sequence tags of a common wheat cultivar and its asymmetric somatic hybrid line. Asymmetric somatic hybridization affected SCUB and promoted the bias to A- and T-ending synonymous codon (SCs). SCUB frequencies in chromosomes introgressed with exogenous fragments were comparable to those in chromosomes without exogenous fragments, showing that exogenous fragments had no local chromosomal effect. Asymmetric somatic hybridization affected SCUB frequencies in indel-flanking sequences more strongly than in non-flanking sequences, and this stronger effect was present in both chromosomes with and without exogenous fragments. DNA methylation-driven SCUB shift was more pronounced than other SC pairs. SCUB shift was similar among seven groups of allelic chromosomes as well as three sub-genomes. Our work demonstrates that the SCUB shift induced by asymmetric somatic hybridization is attributed to the whole genomic shock, and DNA methylation is a putative force of SCUB shift during asymmetric somatic hybridization. Asymmetric somatic hybridization provides an available method for deepening the nature of SCUB shift and genetic variation induced by genomic shock.
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http://dx.doi.org/10.3389/fgene.2021.682324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226224PMC
June 2021

Enhanced lipid production by addition of malic acid in fermentation of recombinant Mucor circinelloides Mc-MT-2.

Sci Rep 2021 Jun 16;11(1):12674. Epub 2021 Jun 16.

Colin Ratledge Center for Microbial Lipids, School of Agricultural Engineering and Food Science, Shandong University of Technology, 266 Xincun West Road, Zibo, 255000, People's Republic of China.

In our previous work, we reported a novel approach for increasing lipid production in an oleaginous fungus Mucor circinelloides by overexpression of mitochondrial malate transporter protein. This transporter plays a vital role in fatty acid biosynthesis during malate and citrate transport systems in oleaginous fungi. In this study, the controlling metabolic supplementation strategy was used to improve the lipid production by overexpression of malate transporter protein in M. circinelloides strain coded as Mc-MT-2. The effects of different metabolic intermediates on lipid production in batch fermentation by Mc-MT-2 were investigated. The optimal lipid production was obtained at 0.8% malic acid after 24 h of fermentation. Furthermore, in fed-batch bioreactors containing glucose as a carbon source supplemented with malic acid, the highest cell growth, and lipid production were achieved. The resulting strain showed the fungal dry biomass of 16 g/L, a lipid content of 32%, lipid yield of 5.12 g/L in a controlled bench-top bioreactor, with 1.60-, 1.60- and 2.56-fold improvement, respectively, compared with the batch control without supplementation of malic acid. Our findings revealed that the addition of malic acid during fermentation might play an important role in lipid accumulation in the recombinant M. circinelloides Mc-MT-2. This study provides valuable insights for enhanced microbial lipid production through metabolic supplementation strategy in large scale and industrial applications.
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http://dx.doi.org/10.1038/s41598-021-92324-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208983PMC
June 2021

Safety and immunogenicity of a quadrivalent inactivated subunit non-adjuvanted influenza vaccine: A randomized, double-blind, active-controlled phase 1 clinical trial.

Vaccine 2021 06 1;39(29):3871-3878. Epub 2021 Jun 1.

Department of Research and Development, Ab&B Biotech Co., Ltd, Taizhou, Jiangsu, China; Department of Research and Development, Yither Biotech Co., Ltd, Shanghai, China. Electronic address:

Quadrivalent influenza inactivated vaccine (IIV4) is more likely to provide wider protection against yearly circulating influenza viruses than trivalent inactivated influenza vaccine (IIV3). In this study, a total of 320 participants were allocated to four age cohorts (6-35 months, 3-8 years, 9-17 years, and ≥ 18 years; 80 participants/cohort) according to their actual date of birth. Participants in each cohort were randomly assigned to two groups to receive intramuscular injection of the trial vaccine or the comparative vaccine in a one-dose (3-8 years, 9-17 years,and ≥ 18 years) schedule on day 0 or two-dose (6-35 months cohort) schedule on day 0 and 28. The first objective is to evaluate the safety and immunogenicity of the full-dose subunit non-adjuvanted IIV4 (FD-subunit NAIIV4) we developed versus an active-control, China-licensed split-virion NAIIV4, in people ≥ 3 years. The second objective is to evaluate the safety and immunogenicity of FD-subunit NAIIV4 versus the half-dose (HD-subunit NAIIV4) in toddlers aged 6-35 months. Results showed that all adverse reactions noted were rare, mild, and self-limited. In ≥ 3 years cohorts, systemic adverse reactions in FD-subunit NAIIV4 groups were less than the active control split-virion NAIIV4 groups ([Systemic adverse reaction rates (95%CI)], 15.0 (8.6-21.4) versus 19.2(12.1-26.2), p = 0.391). The overall seroprotection efficacy after vaccination were comparable between FD-subunit NAIIV4 and the active control split-virion NAIIV4([Seroprotection rates (95%CI)], H1N1, 99.2(81.3-100.0) versus 94.9(90.9-98.9), p = 0.117; H3N2, 81.7(74.7-88.6) versus 82.1(75.1-89.0), p = 0.939; BV, 75.8(68.2-83.5) versus 74.4(66.4-82.3), p = 0.793; BY, 94.2(90.0-98.4) versus 92.3(87.5-97.1), p = 0.568). Additionally, FD-subunit NAIIV4 has comparable safety and better seroprotection versus that of the half-dose in 6-35 months toddlers groups ([Total adverse reaction rates (95%CI)], 37.5(18.5-56.5) versus 47.5(26.1-68.9), p = 0.366) ([Seroprotection rates (95%CI)], H1N1, 85(56.4-100.0) versus 75.7(47.6-100.0), p = 0.117; H3N2, 50(28.1-71.9) versus 29.7(12.2-47.3), p = 0.070; BV, 75(48.2-100.0) versus 29.7(12.2-47.3), p < 0.001; BY, 75(48.2-100.0) versus 56.8(32.5-81.0), p = 0.091). As a result, the FD-subunit NAIIV4 we developed is safe and effective to provide broader and adequate protection against the circulating influenza viruses during 2018-2019, which could be an essential component of the global preventive strategy for influenza pandemic.
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http://dx.doi.org/10.1016/j.vaccine.2021.05.070DOI Listing
June 2021

The alveolar epithelial cells are involved in pulmonary vascular remodeling and constriction of hypoxic pulmonary hypertension.

Respir Res 2021 May 4;22(1):134. Epub 2021 May 4.

Department of Pathophysiology, School of Basic Medicine, Fourth Military Medical University, 169 Changle Western Street, Xi'an, Shaanxi, 710032, People's Republic of China.

Background: Hypoxic pulmonary hypertension (HPH) is a common type of pulmonary hypertension and characterized by pulmonary vascular remodeling and constriction. Alveolar epithelial cells (AECs) primarily sense alveolar hypoxia, but the role of AECs in HPH remains unclear. In this study, we explored whether AECs are involved in pulmonary vascular remodeling and constriction.

Methods: In the constructed rat HPH model, hemodynamic and morphological characteristics were measured. By treating AECs with hypoxia, we further detected the levels of superoxide dismutase 2 (SOD2), catalase (CAT), reactive oxygen species (ROS) and hydrogen peroxide (HO), respectively. To detect the effects of AECs on pulmonary vascular remodeling and constriction, AECs and pulmonary artery smooth cells (PASMCs) were co-cultured under hypoxia, and PASMCs and isolated pulmonary artery (PA) were treated with AECs hypoxic culture medium. In addition, to explore the mechanism of AECs on pulmonary vascular remodeling and constriction, ROS inhibitor N-acetylcysteine (NAC) was used.

Results: Hypoxia caused pulmonary vascular remodeling and increased pulmonary artery pressure, but had little effect on non-pulmonary vessels in vivo. Meanwhile, in vitro, hypoxia promoted the imbalance of SOD2 and CAT in AECs, leading to increased ROS and hydrogen peroxide (HO) production in the AECs culture medium. In addition, AECs caused the proliferation of co-cultured PASMCs under hypoxia, and the hypoxic culture medium of AECs enhanced the constriction of isolated PA. However, treatment with ROS inhibitor NAC effectively alleviated the above effects.

Conclusion: The findings of present study demonstrated that AECs were involved in pulmonary vascular remodeling and constriction under hypoxia by paracrine HO into the pulmonary vascular microenvironment.
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http://dx.doi.org/10.1186/s12931-021-01708-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8094493PMC
May 2021

Survey on Public Psychological Intervention Demand and Influence Factors Analysis.

Int J Environ Res Public Health 2021 04 30;18(9). Epub 2021 Apr 30.

Arts and Sciences School, Translation and Cultural Communication Research Institute, Shaanxi University of Science and Technology, Xi'an 710000, China.

Major public health emergencies would have a negative influence on the psychology of the public, and an effective psychological intervention can help them to relieve some emotions, such as tension and panic. However, differences in individual environments affect people's psychological intervention demands and intervention mode choices. Therefore, it is of great theoretical and practical value to analyze and identify the key factors affecting these demands and choices. Based on a nationwide sample of 24,188 respondents from the "Internet Survey of Residents' Behavioral Changes and Psychological Conditions during the Epidemic," the different characteristics of public psychological intervention demands and choices under different factors are explored in this paper. The results demonstrate that: (1) the psychological status of Chinese people was relatively stable during the epidemic period, and there were 1016 respondents who had subjective demands for a psychological intervention, (2) age, gender, occupation type, residence, family size, risk perception, psychological status, education level, and fixed expenditure all significantly affect public psychological intervention demands, and (3) risk perception, psychological status, age, gender, and family size will impact the choice of psychological intervention methods. The above results can provide a decision-making basis for the construction of a psychological intervention system in psychological crisis management during the post-epidemic prevention and control period, as well as reference and suggestions for handling psychological stress of similar sudden crisis events in the future.
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http://dx.doi.org/10.3390/ijerph18094808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124959PMC
April 2021

Tunable Electrocatalytic Behavior of Sodiated MoS Active Sites toward Efficient Sulfur Redox Reactions in Room-Temperature Na-S Batteries.

Adv Mater 2021 Apr 17;33(16):e2100229. Epub 2021 Mar 17.

College of Chemistry and Molecular Sciences, Hubei Key Laboratory of Electrochemical Power Sources, Wuhan University, Wuhan, 430072, P. R. China.

Room-temperature (RT) sodium-sulfur (Na-S) batteries hold great promise for large-scale energy storage due to the advantages of high energy density, low cost, and resource abundance. The research progress on RT Na-S batteries, however, has been greatly hindered by the sluggish kinetics of the sulfur redox reactions. Herein, an elaborate multifunctional architecture, consisting of N-doped carbon skeletons and tunable MoS sulfiphilic sites, is fabricated via a simple one-pot reaction followed by in situ sulfurization. Beyond the physical confinement and chemical binding of polarized N-doped carbonaceous microflowers, the MoS active sites play a key role in catalyzing polysulfide redox reactions, especially the conversion from long-chain Na S (4 ≤ n ≤ 8) to short-chain Na S and Na S. Significantly, the electrocatalytic activity of MoS can be tunable via adjusting the discharge depth. It is remarkable that the sodiated MoS exhibits much stronger binding energy and electrocatalytic behavior compared to MoS sites, effectively enhancing the formation of the final Na S product. Consequently, the S cathode achieves superior electrochemical performance in RT Na-S batteries, delivering a high capacity of 774.2 mAh g after 800 cycles at 0.2 A g , and an ultrahigh capacity retention with a capacity decay rate of only 0.0055% per cycle over 2800 cycles.
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http://dx.doi.org/10.1002/adma.202100229DOI Listing
April 2021

Anxiety and depression are risk factors for recurrent pregnancy loss: a nested case-control study.

Health Qual Life Outcomes 2021 Mar 8;19(1):78. Epub 2021 Mar 8.

Department of Scientific Research Center of Gansu Provincial Maternity and Child-Care Hospital, No.143. Qilihe North Rd., Lanzhou, 730050, Gansu, People's Republic of China.

Background: To evaluate the interaction of depression and anxiety with the development of recurrent pregnancy loss (RPL).

Methods: A nested case-control study involving 2558 participants was conducted with data from the prospective Miscarriage Woman Cohort study between 2017 and 2019 in the province of Gansu, China. The questionnaire data, self-rating anxiety scale and self-rating depression scale were collected after each participant's first miscarriage. Information on RPL outcomes was obtained from the medical records within the subsequent 2 years. All patients diagosed RPL were recruited as cases whilst a randomly selected group of women with only one miscarriage in the past were recruited as controls. The logistic regression and the interaction effects between anxiety and depression and RPL were analysed.

Results: The prevalence of anxiety (n = 325, 28.7% vs. n = 278, 19.5%) and depression symptoms (n = 550, 48.6% vs. n = 589, 41.3%) for the 1132 RPL cases were higher than 1426 non-RPL controls (P < 0.001). After adjusting for possible confounding variables, the odds ratio (OR) value, reflecting the multiplicative interaction, was 1.91 (95% CI 1.50-2.44, P < 0.001) for cases with both anxiety and depression symptoms compared with the non-RPL group. The relative excess risk of interaction value, reflecting the additive interaction between anxiety and depression to RPL was 1.15 (95% CI 0.32-4.21). Moreover, the adjusted OR for RPL cases with mild anxiety and severe depression was 2.77 (95% CI 1.07-44.14, P < 0.001), for RPL cases with severe anxiety and mild depression was 4.23 (95% CI 1.01-22.21, P < 0.001), for RPL cases with severe anxiety and moderate depression was 4.34 (95% CI 1.03-21.28, P < 0.001) and for RPL cases with severe anxiety and severe depression was 5.95 (95% CI 1.09-45.09, P < 0.05).

Conclusions: Either depression or anxiety alone could increase the risk of subsequent RPL. Anxiety and depression had a synergistic effect after the first miscarriage which increased the development of subsequent RPL disease.
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http://dx.doi.org/10.1186/s12955-021-01703-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7938475PMC
March 2021

Prognostic values, ceRNA network, and immune regulation function of SDPR in KRAS-mutant lung cancer.

Cancer Cell Int 2021 Jan 12;21(1):49. Epub 2021 Jan 12.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, People's Republic of China.

Background: Serum Deprivation Protein Response (SDPR) plays an important role in formation of pulmonary alveoli. However, the functions and values of SDPR in lung cancer remain unknown. We explored prognostic value, expression pattern, and biological function of SDPR in non-small cell lung cancer (NSCLC) and KRAS-mutant lung cancers.

Methods: SDPR expression was evaluated by quantitative real-time PCR (RT-qPCR), immunohistochemistry (IHC), and Western blot on human NSCLC cells, lung adenocarcinoma tissue array, KRAS-mutant transgenic mice, TCGA and GEO datasets. Prognostic values of SDPR were evaluated by Kaplan-Meier and Cox regression analysis. Bioinformatics implications of SDPR including SDPR-combined transcription factors (TFs) and microRNAs were predicted. In addition, correlations between SDPR, immune checkpoint molecules, and tumor infiltration models were illustrated.

Results: SDPR expression was downregulated in tumor cells and tissues. Low SDPR expression was an independent factor that correlated with shorter overall survival of patients both in lung cancer and KRAS-mutant subgroups. Meanwhile, ceRNA network was constructed to clarify the regulatory and biological functions of SDPR. Negative correlations were found between SDPR and immune checkpoint molecules (PD-L1, TNFRSF18, TNFRSF9, and TDO2). Moreover, diversity immune infiltration models were observed in NSCLC with different SDPR expression and copy number variation (CNV) patterns.

Conclusions: This study elucidated regulation network of SDPR in KRAS-mutant NSCLC, and it illustrated correlations between low SDPR expression and suppressed immune system, unfolding a prognostic factor and potential target for the treatment of lung cancer, especially for KRAS-mutant NSCLC.
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http://dx.doi.org/10.1186/s12935-021-01756-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7802324PMC
January 2021

Detection of locus-specific -methyladenosine modification based on Ag-assisted ligation and supersandwich signal amplification.

Analyst 2021 Feb;146(4):1355-1360

State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210023, P. R. China.

Emerging evidence reveals that the epitranscriptomic mark N6-methyladenosine (m6A) plays vital roles in organisms, including gene regulation and disease progression. However, developing sensitive methods to detect m6A modification, especially the identification of m6A marks at the single-site level, remains a challenge. Therefore, based on target-specific triggered signal amplification, we developed a highly sensitive electrochemical method to detect site-specific m6A modifications in DNA. In this work, the m6A site in DNA can restrict the ligation assisted by Ag+, and this restriction effect can activate the subsequent strand displacement reaction and hybridization chain reaction (HCR), thus achieving signal amplification from the m6A site, and finally realizing high sensitivity analysis of m6A methylation. Benefiting from the high specificity of base pairs and the extremely weak binding affinity between Ag+ and m6A, the proposed method was used for not only detecting the target DNA with a putative m6A site, but also identifying m6A marks at the single-site level in DNA. In addition, this study does not rely on antibodies and radiolabeling, so it has the advantage of cost-effectiveness. Therefore, we believe that the proposed strategy may provide a new perspective for methylation research, which can be used to test more clinical samples in further research.
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http://dx.doi.org/10.1039/d0an02214dDOI Listing
February 2021

Dihydroartemisinin Sensitizes Esophageal Squamous Cell Carcinoma to Cisplatin by Inhibiting Sonic Hedgehog Signaling.

Front Cell Dev Biol 2020 10;8:596788. Epub 2020 Dec 10.

Department of Gastroenterology, The Seventh Medical Center, Chinese PLA General Hospital, Beijing, China.

Platinum-based regimens have been routinely used in the clinical treatment of patients with esophageal squamous cell carcinoma (ESCC). However, administration of these drugs is frequently accompanied by drug resistance. Revealing the underlying mechanisms of the drug resistance and developing agents that enhance the sensitivity to platinum may provide new therapeutic strategies for the patients. In the present study, we found that the poor outcome of ESCC patients receiving platinum-based regimens was associated with co-expression of Shh and Sox2. The sensitivity of ESCC cell lines to cisplatin was related to their activity of Shh signaling. Manipulating of Shh expression markedly changed the sensitivity of ESCC cells to platinum. Continuous treatment with cisplatin resulted in the activation of Shh signaling and enhanced cancer stem cell-like phenotypes in ESCC cells. Dihydroartemisinin (DHA), a classic antimalarial drug, was identified as a novel inhibitor of Shh pathway. Treatment with DHA attenuated the cisplatin-induced activation of the Shh pathway in ESCC cells and synergized the inhibitory effect of cisplatin on proliferation, sphere and colony formation of ALDH-positive ESCC cells and growth of ESCC cell-derived xenograft tumors . Taken together, these results demonstrate that the Shh pathway is an important player in cisplatin-resistant ESCC and DHA acts as a promising therapeutic agent to sensitize ESCC to cisplatin treatment.
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http://dx.doi.org/10.3389/fcell.2020.596788DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7758349PMC
December 2020

Polyploidization is accompanied by synonymous codon usage bias in the chloroplast genomes of both cotton and wheat.

PLoS One 2020 19;15(11):e0242624. Epub 2020 Nov 19.

The Key Laboratory of Plant Development and Environmental Adaption, Ministry of Education, School of Life Science, Shandong University, Jinan, Shandong, China.

Synonymous codon usage bias (SCUB) of both nuclear and organellar genes can mirror the evolutionary specialization of plants. The polyploidization process exposes the nucleus to genomic shock, a syndrome which promotes, among other genetic variants, SCUB. Its effect on organellar genes has not, however, been widely addressed. The present analysis targeted the chloroplast genomes of two leading polyploid crop species, namely cotton and bread wheat. The frequency of codons in the chloroplast genomes ending in either adenosine (NNA) or thymine (NNT) proved to be higher than those ending in either guanidine or cytosine (NNG or NNC), and this difference was conserved when comparisons were made between polyploid and diploid forms in both the cotton and wheat taxa. Preference for NNA/T codons was heterogeneous among genes with various numbers of introns and was also differential among the exons. SCUB patterns distinguished tetraploid cotton from its diploid progenitor species, as well as bread wheat from its diploid/tetraploid progenitor species, indicating that SCUB in the chloroplast genome partially mirrors the formation of polyploidies.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0242624PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676672PMC
January 2021

Safety and immunogenicity of an inactivated SARS-CoV-2 vaccine, BBIBP-CorV: a randomised, double-blind, placebo-controlled, phase 1/2 trial.

Lancet Infect Dis 2021 01 15;21(1):39-51. Epub 2020 Oct 15.

Chinese Center for Disease Control and Prevention, Beijing, China.

Background: The ongoing COVID-19 pandemic warrants accelerated efforts to test vaccine candidates. We aimed to assess the safety and immunogenicity of an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine candidate, BBIBP-CorV, in humans.

Methods: We did a randomised, double-blind, placebo-controlled, phase 1/2 trial at Shangqiu City Liangyuan District Center for Disease Control and Prevention in Henan Province, China. In phase 1, healthy people aged 18-80 years, who were negative for serum-specific IgM/IgG antibodies against SARS-CoV-2 at the time of screening, were separated into two age groups (18-59 years and ≥60 years) and randomly assigned to receive vaccine or placebo in a two-dose schedule of 2 μg, 4 μg, or 8 μg on days 0 and 28. In phase 2, healthy adults (aged 18-59 years) were randomly assigned (1:1:1:1) to receive vaccine or placebo on a single-dose schedule of 8 μg on day 0 or on a two-dose schedule of 4 μg on days 0 and 14, 0 and 21, or 0 and 28. Participants within each cohort were randomly assigned by stratified block randomisation (block size eight) and allocated (3:1) to receive vaccine or placebo. Group allocation was concealed from participants, investigators, and outcome assessors. The primary outcomes were safety and tolerability. The secondary outcome was immunogenicity, assessed as the neutralising antibody responses against infectious SARS-CoV-2. This study is registered with www.chictr.org.cn, ChiCTR2000032459.

Findings: In phase 1, 192 participants were enrolled (mean age 53·7 years [SD 15·6]) and were randomly assigned to receive vaccine (2 μg [n=24], 4 μg [n=24], or 8 μg [n=24] for both age groups [18-59 years and ≥60 years]) or placebo (n=24). At least one adverse reaction was reported within the first 7 days of inoculation in 42 (29%) of 144 vaccine recipients. The most common systematic adverse reaction was fever (18-59 years, one [4%] in the 2 μg group, one [4%] in the 4 μg group, and two [8%] in the 8 μg group; ≥60 years, one [4%] in the 8 μg group). All adverse reactions were mild or moderate in severity. No serious adverse event was reported within 28 days post vaccination. Neutralising antibody geometric mean titres were higher at day 42 in the group aged 18-59 years (87·7 [95% CI 64·9-118·6], 2 μg group; 211·2 [158·9-280·6], 4 μg group; and 228·7 [186·1-281·1], 8 μg group) and the group aged 60 years and older (80·7 [65·4-99·6], 2 μg group; 131·5 [108·2-159·7], 4 μg group; and 170·87 [133·0-219·5], 8 μg group) compared with the placebo group (2·0 [2·0-2·0]). In phase 2, 448 participants were enrolled (mean age 41·7 years [SD 9·9]) and were randomly assigned to receive the vaccine (8 μg on day 0 [n=84] or 4 μg on days 0 and 14 [n=84], days 0 and 21 [n=84], or days 0 and 28 [n=84]) or placebo on the same schedules (n=112). At least one adverse reaction within the first 7 days was reported in 76 (23%) of 336 vaccine recipients (33 [39%], 8 μg day 0; 18 [21%], 4 μg days 0 and 14; 15 [18%], 4 μg days 0 and 21; and ten [12%], 4 μg days 0 and 28). One placebo recipient in the 4 μg days 0 and 21 group reported grade 3 fever, but was self-limited and recovered. All other adverse reactions were mild or moderate in severity. The most common systematic adverse reaction was fever (one [1%], 8 μg day 0; one [1%], 4 μg days 0 and 14; three [4%], 4 μg days 0 and 21; two [2%], 4 μg days 0 and 28). The vaccine-elicited neutralising antibody titres on day 28 were significantly greater in the 4 μg days 0 and 14 (169·5, 95% CI 132·2-217·1), days 0 and 21 (282·7, 221·2-361·4), and days 0 and 28 (218·0, 181·8-261·3) schedules than the 8 μg day 0 schedule (14·7, 11·6-18·8; all p<0·001).

Interpretation: The inactivated SARS-CoV-2 vaccine, BBIBP-CorV, is safe and well tolerated at all tested doses in two age groups. Humoral responses against SARS-CoV-2 were induced in all vaccine recipients on day 42. Two-dose immunisation with 4 μg vaccine on days 0 and 21 or days 0 and 28 achieved higher neutralising antibody titres than the single 8 μg dose or 4 μg dose on days 0 and 14.

Funding: National Program on Key Research Project of China, National Mega projects of China for Major Infectious Diseases, National Mega Projects of China for New Drug Creation, and Beijing Science and Technology Plan.
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http://dx.doi.org/10.1016/S1473-3099(20)30831-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7561304PMC
January 2021

Prevalence and Correlation of Anxiety, Insomnia and Somatic Symptoms in a Chinese Population During the COVID-19 Epidemic.

Front Psychiatry 2020 28;11:568329. Epub 2020 Aug 28.

Department of Psychiatry, The Affiliated Brain Hospital of Guangzhou Medical University (Guangzhou Huiai Hospital), Guangzhou, China.

Background: Anxiety has been a common mental state during the epidemic of Coronavirus Disease 2019 (COVID-19) and is usually closely related to somatization. However, no study on somatization in anxiety and its relationship with insomnia has been conducted. Therefore, this study aimed to identify the prevalence of anxiety, somatization and insomnia and explore the relationships between different psychological states in the general population during the COVID-19 outbreak.

Methods: A total of 1,172 respondents were recruited from 125 cities in mainland China by an online questionnaire survey. All subjects were evaluated with the 7-item Generalized Anxiety Disorder (GAD-7) scale, the somatization subscale of the Symptom Checklist 90-Revised (SCL-90-R), and the 7-item Insomnia Severity Index (ISI).

Results: The percentages of anxiety, somatization, and insomnia were 33.02%, 7.59%, and 24.66%, respectively. The prevalence of somatization was 19.38% in participants with anxiety. Compared to the anxiety without somatization group, the anxiety with somatization group had a significantly higher percentage of patients with a history of physical disease and insomnia, as well as higher GAD-7 scores and SCL-90 somatization subscores (all p < 0.001). The SCL-90 somatization subscores were positively correlated with age, history of physical disease, GAD-7 scores, and ISI scores (all p < 0.001). Furthermore, multivariate logistic regression showed that GAD-7 score, ISI score, and age were risk factors for somatization in the anxious population.

Conclusions: Somatic and psychological symptoms were common in the general population during the COVID-19 outbreak. Somatic symptoms, anxiety, and insomnia are closely related, and improving anxiety and sleep quality may help relieve somatic symptoms.
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http://dx.doi.org/10.3389/fpsyt.2020.568329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485113PMC
August 2020

Metformin attenuates renal interstitial fibrosis through upregulation of Deptor in unilateral ureteral obstruction in rats.

Exp Ther Med 2020 Nov 26;20(5):17. Epub 2020 Aug 26.

Department of Pharmacology, Xuzhou Medical University, Xuzhou, Jiangsu 221000, P.R. China.

Renal interstitial fibrosis (RIF) is a common pathological process that accompanies chronic kidney disease (CKD) and that progresses to end-stage renal failure (ESRD). Accumulating evidence has revealed that persistent mammalian target of rapamycin (mTOR) activation in kidneys is closely associated with the occurrence and progression of CKD. The DEP domain-containing mTOR interacting protein (Deptor) is an endogenous negative regulator of mTOR. Metformin can attenuate renal fibrosis in an animal model of diabetic nephropathy. Previous studies demonstrated that metformin can attenuate renal fibrosis in several models of CKD. However, the precise mechanisms of this effect are not well understood. The present study aimed to examine the mechanism of action of metformin on unilateral ureteral obstruction (UUO)-induced RIF in rats Sprague-Dawley rats were randomly divided into a sham-operated group, three UUO groups examined at different time points (3, 7 and 14 days after UUO surgery), and three metformin-treated groups, treated with three different concentrations of metformin. The metformin-treated groups were administered metformin orally every day for 14 consecutive days following surgery. The protein expression levels of Deptor, α-smooth muscle actin (α-SMA), phosphorylated (p-)mTOR, p-ribosomal protein S6 kinase (p-p70S6K) and CD68 were assessed. The present results suggested that, following UUO, there was a significant reduction of Deptor expression, and an increase in collagen deposition in the extracellular matrix over time, accompanied by an increased expression of several proteins including CD68, α-SMA, p-mTOR and p-p70S6K. Notably, metformin treatment reversed these effects. In conclusion, the present results suggested that metformin attenuated RIF of UUO rats, and the mechanism of action was found to be associated with the increase in Deptor expression and inhibition of the mTOR/p70S6K pathway in the kidneys of UUO rats.
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http://dx.doi.org/10.3892/etm.2020.9144DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471900PMC
November 2020

Effect of an Inactivated Vaccine Against SARS-CoV-2 on Safety and Immunogenicity Outcomes: Interim Analysis of 2 Randomized Clinical Trials.

JAMA 2020 09;324(10):951-960

National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co Ltd, Wuhan, Hubei, China.

Importance: A vaccine against coronavirus disease 2019 (COVID-19) is urgently needed.

Objective: To evaluate the safety and immunogenicity of an investigational inactivated whole-virus COVID-19 vaccine in China.

Interventions: In the phase 1 trial, 96 participants were assigned to 1 of the 3 dose groups (2.5, 5, and 10 μg/dose) and an aluminum hydroxide (alum) adjuvant-only group (n = 24 in each group), and received 3 intramuscular injections at days 0, 28, and 56. In the phase 2 trial, 224 adults were randomized to 5 μg/dose in 2 schedule groups (injections on days 0 and 14 [n = 84] vs alum only [n = 28], and days 0 and 21 [n = 84] vs alum only [n = 28]).

Design, Setting, And Participants: Interim analysis of ongoing randomized, double-blind, placebo-controlled, phase 1 and 2 clinical trials to assess an inactivated COVID-19 vaccine. The trials were conducted in Henan Province, China, among 96 (phase 1) and 224 (phase 2) healthy adults aged between 18 and 59 years. Study enrollment began on April 12, 2020. The interim analysis was conducted on June 16, 2020, and updated on July 27, 2020.

Main Outcomes And Measures: The primary safety outcome was the combined adverse reactions 7 days after each injection, and the primary immunogenicity outcome was neutralizing antibody response 14 days after the whole-course vaccination, which was measured by a 50% plaque reduction neutralization test against live severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Results: Among 320 patients who were randomized (mean age, 42.8 years; 200 women [62.5%]), all completed the trial up to 28 days after the whole-course vaccination. The 7-day adverse reactions occurred in 3 (12.5%), 5 (20.8%), 4 (16.7%), and 6 (25.0%) patients in the alum only, low-dose, medium-dose, and high-dose groups, respectively, in the phase 1 trial; and in 5 (6.0%) and 4 (14.3%) patients who received injections on days 0 and 14 for vaccine and alum only, and 16 (19.0%) and 5 (17.9%) patients who received injections on days 0 and 21 for vaccine and alum only, respectively, in the phase 2 trial. The most common adverse reaction was injection site pain, followed by fever, which were mild and self-limiting; no serious adverse reactions were noted. The geometric mean titers of neutralizing antibodies in the low-, medium-, and high-dose groups at day 14 after 3 injections were 316 (95% CI, 218-457), 206 (95% CI, 123-343), and 297 (95% CI, 208-424), respectively, in the phase 1 trial, and were 121 (95% CI, 95-154) and 247 (95% CI, 176-345) at day 14 after 2 injections in participants receiving vaccine on days 0 and 14 and on days 0 and 21, respectively, in the phase 2 trial. There were no detectable antibody responses in all alum-only groups.

Conclusions And Relevance: In this interim report of the phase 1 and phase 2 trials of an inactivated COVID-19 vaccine, patients had a low rate of adverse reactions and demonstrated immunogenicity; the study is ongoing. Efficacy and longer-term adverse event assessment will require phase 3 trials.

Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000031809.
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http://dx.doi.org/10.1001/jama.2020.15543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426884PMC
September 2020

Safety and immunogenicity of an alum-adjuvanted whole-virion H7N9 influenza vaccine: a randomized, blinded, clinical trial.

Clin Microbiol Infect 2020 Jul 29. Epub 2020 Jul 29.

Henan Province Centre for Disease Control and Prevention, Centre of Vaccine Clinical Research, China. Electronic address:

Objectives: A case of H7N9 influenza virus infection was first identified in China in 2013. This virus is considered to have high pandemic potential. Here we developed an H7N9 influenza vaccine containing an aluminium adjuvant and evaluated the safety and immunogenicity of the vaccine.

Methods: From October 2017 through August 2018 we conducted a randomized, double-blinded, single-centre phase I clinical trial in China among 360 participants aged ≥12 years. All participants received two doses of the vaccine (7.5, 15 or 30 μg haemagglutinin antigen) or placebo at an interval of 21 days. Adverse event data were collected for 30 days after vaccination. Serum samples were collected on days 0, 21 and 42 for the haemagglutinin inhibition (HI) antibody assay.

Results: A total of 347 participants (347/360, 96.4%) completed the study. The proportions of vaccine-related adverse events after one injection were 56.7% (34/60) in the 7.5-μg group, 86.7% (52/60) in the 15-μg group and 86.7% (52/60) in the 30-μg group. The proportions of adverse events after two injections were less than those reported after the first dose. None of the serious adverse events were related to the vaccine. After receiving two doses of the 7.5-μg vaccine, the proportion of participants achieving an HI titre of ≥40 was 98.2% (55/56, 95%CI 72.3~100.0%), with a geometric mean titre (GMT) of 192.6 (95%CI 162.9~227.8).

Conclusions: The alum-adjuvanted H7N9 whole-virion inactivated vaccine was safe and strongly immunogenic in a population aged ≥12 years.
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http://dx.doi.org/10.1016/j.cmi.2020.07.033DOI Listing
July 2020

Dual inhibition of VEGF and PARP suppresses KRAS-mutant colorectal cancer.

Neoplasia 2020 09 3;22(9):365-375. Epub 2020 Jul 3.

Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, PR China. Electronic address:

The addition of bevacizumab to chemotherapy has prolonged overall and progression-free survival rates for metastatic colorectal cancer (mCRC). However, KRAS-mutant (KRAS-mut) CRC, lacking an ideal targeted agent, represents an inferior-response subgroup of patients. In the present study, we investigated a combination approach of bevacizumab + olaparib in KRAS-mut CRC in a preclinical setting. The combined therapy effectively prevented tumor growth in a KRAS-mut cancer cell-derived xenograft model, although this effect was not observed in vitro. Under bevacizumab treatment, we detected intratumor hypoxia and impaired homologous recombination repair (HRR), accompanied by vascular regression. We explored the underlying mechanism of this combined therapy by mimicking a hypoxic condition in vitro using cobalt chloride (CoCl). The results showed that hypoxia impairs HRR and therefore sensitized KRAS-mut CRC cell lines HCT-116, SW620, and Lovo to olaparib. Furthermore, under this hypoxic condition, olaparib could arrest the cell cycle in the G2/M phase, increase DNA damage and dramatically induce cell apoptosis in KRAS-mut CRC cells. Taken together, these results indicated that the combination of bevacizumab + olaparib could be a potential therapeutic approach in a KRAS-mut CRC cohort.
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http://dx.doi.org/10.1016/j.neo.2020.06.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7339053PMC
September 2020

Psychometric properties of the mandarin clinical evaluation of language for preschooler's core scale.

J Commun Disord 2020 Sep - Oct;87:106000. Epub 2020 May 24.

Education and Rehabilitation Department, Faculty of Education, East China Normal University, 3663 North Zhongshan Road, Shanghai, 200062, China.

Purpose: To test the psychometric properties of a newly developed Mandarin Clinical Evaluation of Language for Preschooler's Core Scale (MCELP-CS).

Methods: Data were collected from 379 preschool-aged participants, including 81 children with language disorders associated with clinical conditions. The 155-item MCELP-CS consists of five subscales: vocabulary comprehension (VC), sentence comprehension (SC), vocabulary naming (VN), sentence structure imitation (SSI), and story narration (SN). The scale was used to measure the receptive and expressive language abilities of children aged 3-5 years and 11 months. The Peabody Picture Vocabulary Test-revised (PPVT-R) was used to measure the receptive vocabulary abilities among the children (n = 338). The internal consistency, test-retest reliability, structural validity, convergent validity, and diagnostic accuracy were used to evaluate the scale. Differences between age groups were also examined using analysis of variance.

Results: The MCELP-CS had high internal consistency and good test-retest reliability. Fitting indices of the two-factor model from confirmatory factor analysis (CFA), including χ, CFI, TLI, RSEAM, and SRMR, suggested that the model is consistent with the theoretical structure. Significant correlations between the MCELP-CS and PPVT-R showed a high convergent validity. In addition, the scale indicated good diagnostic accuracy in differentiating the language disorders of children with autism, cerebral palsy (CP), and hearing impairment (HI).

Conclusions: The MCELP-CS is a reliable and valid diagnostic tool for language disorders of Mandarin-speaking preschool children with autism, CP, and HI. It is appropriate to collect normative data for the MCELP-CS with a large sample population of preschool children.
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http://dx.doi.org/10.1016/j.jcomdis.2020.106000DOI Listing
September 2021

A Solvent Co-cross-linked Organogel with Fast Self-Healing Capability and Reversible Adhesiveness at Extreme Temperatures.

ACS Appl Mater Interfaces 2020 Jul 21;12(26):29757-29766. Epub 2020 Jun 21.

Department of Mechanics and Engineering Science, Beijing Innovation Center for Engineering Science and Advanced Technology, College of Engineering, Peking University, Beijing 100871, China.

Antifreezing gels are promising in diverse engineering applications such as structural soft matters, sensors, and wearable devices. However, the capability of fast self-healing and reversible adhesiveness still remain a huge challenge for gels at extreme temperatures. Here, we proposed a solvent-involved cross-linking system composed of polyacrylic acid, polyvinyl alcohol, borax, ethylene glycol, and water, capable of antifreezing below -90 °C. It was not only antifreezing, anticrystalline, and abundant in dynamic bonds but also highly transparent, stretchable (over 800%), and conductive over the scope of temperature from -60 to 60 °C. Moreover, this gel could self-heal within 1 min and repeatedly adhere to multiple substrates including glass, metal, and rubber with an adhesive strength greater than 18 kPa. These key functions of the gel could be mostly preserved after 5 days of storage at 70% relative humidity. It is anticipated that our research opens a new scope for high-performance extreme environment-tolerant adhesives or wearable devices.
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http://dx.doi.org/10.1021/acsami.0c04933DOI Listing
July 2020

Effects of Astaxanthin on Inflammation and Insulin Resistance in a Mouse Model of Gestational Diabetes Mellitus.

Dose Response 2020 Apr-Jun;18(2):1559325820926765. Epub 2020 May 20.

Department of Obstetrics, Northwest Women's and Children's Hospital, Xi'an, Shaanxi, China.

Gestational diabetes mellitus (GDM) is a condition in which a hormone made by the placenta prevents the body from using insulin effectively. It is important to find an effective treatment. A mouse model of GDM was used to testify the effects of astaxanthin on glucose tolerance and insulin sensitivity. Production of inflammatory cytokines, reactive oxygen species (ROS), and glucose transporter type 4 (GLUT4) translocation and insulin-related signaling were measured in the presence of astaxanthin both in vivo and in vitro. It was found that astaxanthin improved insulin sensitivity, glucose tolerance, and litter size of offspring and reduced birth weight of offspring and inflammation in GDM mouse. Moreover, astaxanthin increased GLUT4 translocating to membrane without altering its secretion/expression and glucose uptake and consumption in C2C12 skeletal muscle cells. Furthermore, ROS generation and insulin-related signaling inhibited by tumor necrosis factor α was restored by astaxanthin. It is concluded that astaxanthin has the potential to attenuate GDM symptoms by regulating inflammation and insulin resistance in skeletal muscle of pregnant mice. Our findings suggest that astaxanthin could be a promising and effective molecule to treat GDM.
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http://dx.doi.org/10.1177/1559325820926765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241269PMC
May 2020

Effect of pH on properties of golden pompano skin collagen-based fibril gels by self-assembly in vitro.

J Sci Food Agric 2020 Oct 22;100(13):4801-4807. Epub 2020 Jun 22.

College of Food and Biological Engineering, Jimei University, Xiamen, China.

Background: Application of fish skin collagen has received increasing attention due to mammalian derived diseases and religious limitations. Collagen fibril gel could be formed in vitro through the self-assembly process. The present study investigated the effect of pH on the self-assembly in vitro of acid-solubilized collagen (ASC) from golden pompano skin by determining the turbidity, rheological viscoelasticity, network structure, gel strength, and thermal stability of collagen fibril gel.

Results: The isoelectric point of ASC was pH 5.27. The turbidity-time and rheological viscoelasticity results indicate that the collagen self-assembly rate in vitro at pH 7.0 was the slowest. The rate was accelerated by increasing or decreasing the pH. Scanning electron microscopy images show that the fibril diameters of the collagen fibril gels and the collagenous fibril number in the collagen fiber increased with the pH. The gel strength of the collagen fibril gel prepared at pH 5.0 was 22.06 g and increased up to 220.46 g when pH increased to 8.0. No obvious peaks were observed in the differential scanning calorimetry curves of the collagen fibril gels prepared at pH 5.0, whereas high endothermic peak temperature (T ) and enthalpy change (ΔH) were found in the collagen fibril gels prepared at pH 6.0-8.0.

Conclusion: It is concluded that the physical properties of ASC fibril gels can be improved by increasing the fibril diameter controlled by pH. © 2020 Society of Chemical Industry.
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http://dx.doi.org/10.1002/jsfa.10539DOI Listing
October 2020

Metabolomics-guided analysis reveals a two-step epimerization of deoxynivalenol catalyzed by the bacterial consortium IFSN-C1.

Appl Microbiol Biotechnol 2020 Jul 21;104(13):6045-6056. Epub 2020 May 21.

Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base, Ministry of Science and Technology/ Key Laboratory for Control Technology and Standard for Agro-product Safety and Quality, Ministry of Agriculture and Rural Affairs/ Key Laboratory for Agro-product Safety Risk Evaluation (Nanjing), Ministry of Agriculture and Rural Affairs/ Collaborative Innovation Center for Modern Grain Circulation and Safety/ Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences, Nanjing, People's Republic of China.

Deoxynivalenol (DON) is commonly found in wheat and wheat-derived foods, posing a threat to human health. Biodegradation is an efficient and eco-friendly measure for mycotoxin detoxification. Understanding the mechanism of DON biodegradation is hence of great importance. Herein, we report the application of metabolomics methods for the analysis of DON degradation by a bacterial consortium isolated from wheat leaves collected in Jiangsu Province. Metabolomics analysis combined with a nuclear magnetic resonance analysis revealed the main degradation product, 3-keto-DON, and a minor degradation product, 3-epi-DON. Further study illustrated that DON underwent a two-step epimerization through the intermediate 3-keto-DON. Sequencing analysis of the 16S rRNA metagenome of the microorganismal community suggested that the abundance of three bacterial genera, Achromobacter, Sphingopyxis, and Sphingomonas, substantially increased during the coculture of bacterial consortium and DON. Further investigation revealed that Devosia sp. might be responsible for the epimerization of 3-keto-DON. These findings shed light on the catabolic pathways of DON during biodegradation and illustrate the potential of using metabolomics approaches in biodegradation studies.Key Points• A bacterial consortium was isolated with good deoxynivalenol-degrading potential. • Metabolomics approaches were successfully used to interpret the degradation pathway. • A trace-amount degradation product was determined by metabolomics and NMR analysis. Graphical Abstract .
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http://dx.doi.org/10.1007/s00253-020-10673-1DOI Listing
July 2020

Exploration of the Two-Way Adjustment Mechanism of et for Cardiovascular Diseases.

Comb Chem High Throughput Screen 2020 ;23(10):1100-1112

School of Pharmacy, Shaanxi University of Chinese Medicine, Xianyang, Shaanxi, China.

Aim And Objective: Myocardial infarction, cerebral infarction, and other diseases caused by vascular obstruction have always jeopardized human life and health. Several reports indicate that Rhei Radix et Rhizoma has a good clinical effect in the prevention and treatment of cardiovascular diseases. Owing to the complexity of herbal medicine, the pharmacodynamic mechanism of Rhei Radix et Rhizoma is still unclear. The objectives of this study were to explore the two-way adjustment mechanism of Rhei Radix et Rhizoma and provide a new solution for the prevention and treatment of cardiovascular disease.

Materials And Methods: This study used data mining, reverse pharmacophore matching, network construction, GO and KEGG Analysis, and molecular docking to investigate the two-way adjustment mechanism of Rhei Radix et Rhizoma. The methods used were based on systems pharmacology and big data analysis technology.

Results: The results suggest that Rhei Radix et Rhizoma uses a two-way adjustment of activating blood circulation, as well as blood coagulation in the prevention and treatment of cardiovascular diseases. The components involved in activating blood circulation are mainly anthraquinone components. The corresponding targets are NOS2, NOS3, CALM1, and the corresponding pathways are calcium signaling pathway, VEGF signaling pathway, platelet activation, and the PI3K-Akt signaling pathway. For blood coagulation, the components are mainly tannin components; the corresponding targets are F2, F10, ELANE, and the corresponding pathways are the neuroactive ligand-receptor interaction, complement and coagulation cascades.

Conclusion: This study indicated that Rhei Radix et Rhizoma exerts the two-way adjustment of activating blood circulation and blood coagulation in the prevention and treatment of cardiovascular diseases. It can make up for the side effects of the existing blood circulation drugs for cardiovascular disease, only activating blood circulation, and the uncontrollable large-area bleeding due to the long-term use of the drugs. This study provides a material basis for the development of new blood-activating drugs based on natural medicine.
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http://dx.doi.org/10.2174/1386207323666200521120308DOI Listing
June 2021

Development of glucose oxidase-immobilized alginate nanoparticles for enhanced glucose-triggered insulin delivery in diabetic mice.

Int J Biol Macromol 2020 Sep 16;159:640-647. Epub 2020 May 16.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science & Peking Union Medical College, PR China. Electronic address:

In this work, we successfully developed poly(acrylamido phenylboronic acid)/sodium alginate nanoparticles (NPs) via formation of cycloborates (glucose- and HO-responsive functional groups), as an improved glucose-mediated insulin delivery system loaded with glucose oxidase (GOx). Dynamic light scattering revealed that the GOx-loaded NPs showed better glucose-sensitivity than the GOx-unloaded NPs. In addition, compared to insulin-loaded NPs, the insulin/GOx-loaded NPs displayed faster glucose-responsive insulin release. Importantly, there was a significant hypoglycemic effect on diabetic mice following the subcutaneous injection of insulin/GOx-loaded NPs. Furthermore, the NPs exhibited favorable biocompatibility as demonstrated by cytotoxicity assay, hemolysis study, and histopathological examination. The NPs have the advantages of easy preparation, enhanced glucose-responsiveness, and good biocompatibility, making them as potential candidates for subcutaneous insulin delivery.
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http://dx.doi.org/10.1016/j.ijbiomac.2020.05.097DOI Listing
September 2020

Correlation between oxidative stress and NF-κB signaling pathway in the obesity-asthma mice.

Mol Biol Rep 2020 May 6;47(5):3735-3744. Epub 2020 May 6.

Department of Pediatrics, The Affiliated Hospital of Qingdao University, No. 16, Jiangsu Road, Shinan District, Qingdao, 266003, China.

In this study, a mice model of obesity-asthma was established. We investigated the correlation between oxidative stress and NF-κB signaling pathway in the lung tissues, together with the effects of acetylcysteine. The animals were fed on a high-fat diet, and then ovalbumin (OVA) sensitization was utilized to establish the obesity-asthma model. N-acetylcysteine was used to treat asthma, animals treated with budesonide served as control. The malondialdehyde (MDA) in the lung tissues was determined, together with the activity of glutathione (GSH). EMAS assay was utilized to measure the nuclear factor-κB-P65 (NF-κB-P65) in lung tissues. Western blot analysis was performed to determine the expression of inhibitor kappa B-α (IκB-α) and inhibitor kappa B kinase-β (IKK-β). The MDA in the asthma groups showed significantly elevation (P < 0.01), and the GSH showed significant decrease (P < 0.01), especially in the obesity-asthma group. The efficiency of N-acetylcysteine was superior to that of the budesonide in the decline of MDA and elevation of GSH (P < 0.01). In both asthma groups, the expression of IKK-β and transcription of NF-κB-P65 in the lung tissues showed significant elevation (P < 0.01), and IκB-α showed significant decline (P < 0.01), especially in the obesity-asthma group. There was decline of IKK-β and NF-κB-P65 and elevation of IκB-α in the N-acetylcysteine group, which was even significantly in the Budesonide group (P < 0.01). There was a positive correlation between MDA and NF-κB activation in the lung tissues in all the asthma groups and treatment groups (P < 0.05). Obesity-asthma mice showed higher oxidative stress and activation of NF-κB compared with that of the asthma mice. There was a positive correlation between MDA and NF-κB activation in the lung tissues in the asthma groups. N-acetylcysteine was more effective in reducing the oxidative stress compared to the budesonide.
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http://dx.doi.org/10.1007/s11033-020-05466-8DOI Listing
May 2020

Preparation of a new combination nanoemulsion-encapsulated MAGE1-MAGE3-MAGEn/HSP70 vaccine and study of its immunotherapeutic effect.

Pathol Res Pract 2020 Jun 17;216(6):152954. Epub 2020 Apr 17.

State Key Laboratory of Cancer Biology, Department of Pathology, Xijing Hospital and School of Basic Medicine, Air Force Medical University, Xi'an, 710032, China. Electronic address:

Background: MAGE family genes have been studied as targets for tumor immunotherapy for a long time. Here, we combined MAGE1-, MAGE3- and MAGEn-derived peptides as a cancer vaccine and tested whether a new combination nanoemulsion-encapsulated vaccine could be used to inhibit the growth of tumor cells in humanized SCID mice.

Methods: The nanoemulsion-encapsulated complex protein vaccine (MAGE1, MAGE3, and MAGEn/HSP70 fusion protein; M1M3MnH) was prepared using a magnetic ultrasonic technique. After screening, human PBMCs were injected into SCID mice to mimic the human immune system. Then, the humanized SCID mice were challenged with M3-HHCC cells and immunized with nanoemulsion-encapsulated MAGE1-MAGE3-MAGEn/HSP70 [NE(M1M3MnH)] or M1M3MnH. The cellular immune responses were detected by IFN-γ ELISPOT and cytotoxicity assays. Therapeutic and tumor challenge experiments were also performed.

Results: The results showed that the immune responses elicited by NE(M1M3MnH) were apparently stronger than those elicited by M1M3MnH, NE(-) or PBS, suggesting that this novel nanoemulsion carrier induces potent antitumor immunity against the encapsulated antigens. The results of the therapeutic and tumor challenge experiments also indicated that the new vaccine had a definite effect on SCID mice bearing human hepatic cancer.

Conclusion: Our study indicated that the combination of several tumor antigen-derived peptides may be a relatively good strategy for peptide-based cancer immunotherapy. These results suggest that the complex nanoemulsion vaccine could have broader applications for both therapy and prevention mediated by antitumor effects in the future.
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http://dx.doi.org/10.1016/j.prp.2020.152954DOI Listing
June 2020
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