Publications by authors named "Bo Yan"

577 Publications

Comprehensive determination of transcription start sites derived from all RNA polymerases using ReCappable-seq.

Genome Res 2021 Nov 23. Epub 2021 Nov 23.

New England Biolabs, Inc.

Determination of eukaryotic Transcription Start Sites (TSS) has been based on methods that require the cap structure at the 5-prime end of transcripts derived from Pol-II RNA polymerase. Consequently, these methods do not reveal TSS derived from the other RNA polymerases which also play critical roles in various cell functions. To address this limitation, we developed ReCappable-seq which comprehensively identifies TSS for both Pol-lI and non-Pol-II transcripts at single-nucleotide resolution. The method relies on specific enzymatic exchange of 5-prime m7G caps and 5-prime triphosphates with a selectable tag. When applied to human transcriptomes, ReCappable-seq identifies Pol-II TSS that are in agreement with orthogonal methods such as CAGE. Additionally, ReCappable-seq reveals a rich landscape of TSS associated with Pol-III transcripts which have not previously been amenable to study at genome-wide scale. Novel TSS from non-Pol-II transcription can be located in the nuclear and mitochondrial genomes. ReCappable-seq interrogates the regulatory landscape of coding and noncoding RNA concurrently and enables the classification of epigenetic profiles associated with Pol-lI and non-Pol-II TSS.
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http://dx.doi.org/10.1101/gr.275784.121DOI Listing
November 2021

Distribution and density of tertiary lymphoid structures predict clinical outcome in intrahepatic cholangiocarcinoma.

J Hepatol 2021 Nov 15. Epub 2021 Nov 15.

Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, and Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Fudan University, Shanghai 200032, China; Institute of Biomedical Sciences, Fudan University, Shanghai 200032, China; Center for Tumor Diagnosis & Therapy, Jinshan Hospital, Fudan University, Shanghai 200540, China; State Key Laboratory of Genetic Engineering, Fudan University, Shanghai 200433, China. Electronic address:

Background & Aims: To investigate the prognostic value and relevant mechanisms of tertiary lymphoid structures (TLSs) in intrahepatic cholangiocarcinoma (iCCA).

Methods: We retrospectively included 962 patients from three cancer centers across China. The TLSs at different anatomic subregions were quantified and correlated with overall survival (OS) by Cox regression and Kaplan-Meier analyses. Multiplex immunohistochemistry (mIHC) was applied to characterize the composition of TLSs in 39 iCCA samples.

Results: A quaternary TLS scoring system was established for intra-tumor region (T score) and peri-tumor region (P score) respectively. T score positively correlated with favorable prognosis (P<0.001), whereas a high P score signified a worse survival (P<0.001). Then, mIHC demonstrated that both Tfh and Treg cells were significantly increased in intra-tumor TLSs than peri-tumor counterparts (P<0.05), and Treg cell frequencies within intra-tumor TLSs were positively associated with P score (P<0.05) rather than T score. Collectively, the combination of T and P scores stratified iCCAs into four Immune Classes with distinct prognosis (P<0.001) that differed in the abundance and distribution pattern of TLSs. Patients displayed an immune active pattern had the lowest risk, with 5-year OS rates of 68.8%, whereas only 3.4% of patients with immune excluded pattern survived at 5 years (P<0.001). The C-index of the Immune Class was statistically higher than the TNM staging system (0.73 vs 0.63, P<0.001). These results were validated in an internal and two external cohorts.

Conclusions: The spatial distribution and abundance of TLSs significantly correlated with prognosis and provided a useful immune classification for iCCA. Tfh and Treg cells may play a critical role in determining the functional orientation of spatially different TLSs.

Lay Summary: Tertiary lymphoid structures (TLSs) have been attracting extensive attentions as they are associated with favorable prognosis through activating endogenous anti-tumor immune response. However, their role in intrahepatic cholangiocarcinoma (iCCA) remains elusive. Herein, we comprehensively evaluated the spatial distribution, abundance, and cellular composition of TLSs in iCCA, and revealed opposite prognostic impacts of TLSs located within or outside tumor region. The heterogeneous distribution of Tfh and Treg cells within the spatially different TLSs might be determinant of their functional state. Successfully, the integrated analysis of TLSs stratified iCCAs into four immune subclasses with distinct clinical outcomes.
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http://dx.doi.org/10.1016/j.jhep.2021.10.030DOI Listing
November 2021

Red blood cell distribution width-standard deviation but not red blood cell distribution width-coefficient of variation as a potential index for the diagnosis of iron-deficiency anemia in mid-pregnancy women.

Open Life Sci 2021 6;16(1):1213-1218. Epub 2021 Nov 6.

Department of Medical Technology, Anhui Medical College, Hefei, Anhui Province, 230601, People's Republic of China.

The aim of this study was to compare the diagnostic values of red blood cell distribution width-coefficient of variation (RDW-CV) and red blood cell distribution width-standard deviation (RDW-SD) in mid-pregnancy women with iron deficiency anemia (IDA). To obtain the results, 115 mid-pregnancy women with IDA, defined as the IDA group, and 142 healthy mid-pregnancy women, selected as the control group, were enrolled in this study. Hematological parameters and ferritin concentrations in the serum were analyzed. The efficiency of RDW-CV and RDW-SD to distinguish IDA from mid-pregnancy women was evaluated using receiver operating characteristic (ROC) curves. The RDW-SD value in the IDA group was significantly higher than that in the control group ( < 0.05), while the RDW-CV value did not differ between them ( = 0.84). Significantly negative correlations were found between RDW-CV ( = -0.297, = 0.001), RDW-SD ( = -0.404, = 0.000), and serum ferritin in the IDA group but not in the control group. For the diagnosis of IDA, RDW-CV and RDW-SD produced areas under the ROC curves of 0.58 and 0.84. To conclude, our results suggest that RDW-SD, but not RDW-CV, can be used as a diagnostic index of IDA for mid-pregnancy women.
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http://dx.doi.org/10.1515/biol-2021-0120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8572805PMC
November 2021

Prediction model for aerodynamic coefficients of iced quad bundle conductors based on machine learning method.

R Soc Open Sci 2021 Oct 6;8(10):210568. Epub 2021 Oct 6.

School of Electrical Engineering, Southwest Jiaotong University, Chengdu 611756, People's Republic of China.

The lift, drag and torsional moment coefficients, versus wind attack angle of iced quad bundle conductors in the cases of different conductor structure, ice and wind parameters are numerically simulated and investigated. With the Latin hypercube sampling and numerical simulation, sampling points are designed and datasets are created. Set the number of sub-conductors, wind attack angle, bundle spacing, ice accretion angle, ice thickness, wind velocity and diameter of the conductor as the input variables, a prediction model for the lift, drag and moment coefficients of iced quad bundle conductors is created, trained and tested based on the dataset and extra-trees algorithm. The final integrated prediction model is further validated by applying the aerodynamic coefficients from the prediction model and numerical simulation, respectively, to analyse the galloping features. The developed efficient prediction model for the aerodynamic coefficients of iced quad bundle conductors plays an important role in the quick investigation, prediction and early warning of galloping.
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http://dx.doi.org/10.1098/rsos.210568DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8493202PMC
October 2021

Free-standing graphene aerogel with improved through-plane thermal conductivity after being annealed at high temperature.

J Colloid Interface Sci 2021 Oct 30. Epub 2021 Oct 30.

College of Physical Science and Technology, Xiamen University, Xiamen 361005, China; Jiujiang Research Institute of Xiamen University, Jiujiang 360404, China. Electronic address:

Both high through-plane thermal conductivity and low elastic modulus can reduce thermal interface resistance, which is important for thermal interface materials. The internal porous structure of graphene aerogel (GA) makes it to have a low elastic modulus, which results in its good compressibility. Also, the network structure of GA provides thermal conducting paths, which improve the through-plane thermal conductivity of GA. Annealing GA at 3000 °C helps to remove oxygen-containing functional groups and reduces defects. This greatly improves its crystallinity, which further leads to the improvement of its through-plane thermal conductivity and it has a low modulus of 1.37Mpa. The through-plane thermal conductivity of GA annealed at 3000 °C (GA-3000) was improved as the pressure increased and got to 2.93 W/ m K at a pressure of 1.13 MPa, which is 30 times higher than other graphene-based thermal interface materials (TIMs). These discoveries offer a novel approach for preparing excellent TIMs.
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http://dx.doi.org/10.1016/j.jcis.2021.10.134DOI Listing
October 2021

Carbohydrate antigen 125, carbohydrate antigen 15-3 and low-density lipoprotein as risk factors for intraocular metastases in postmenopausal breast cancer.

Medicine (Baltimore) 2021 Oct;100(43):e27693

Department of Ophthalmology, the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province, China.

Abstract: The prognosis of patients with postmenopausal breast cancer (PBC) could be improved by the early detection of intraocular metastases (IOMs). However, serum biomarkers for IOMs in PBC remain elusive. In the current study, we investigated patients with PBC, and compared serum parameters in an IOM and a non-IOM group, and then differentiated the risk factors related to IOMs. A comparison between an IOM and a non-IOM (NIOM) group was performed using Student t-test and a Chi-Squared test. After constructing a Poisson regression model to identify risk factors, we plotted receiver operating characteristic curves to evaluate the predictive value of significant risk factors in detecting IOMs. The incidence of IOMs in PBC was 1.16%. The histopathology results were not significantly different between the 2 groups. The levels of serum carbohydrate antigen 125 (CA-125), carbohydrate antigen 15-3 (CA15-3) and alkaline phosphatase were significantly elevated in IOMs compared with NIOMs (P = .082, P < .001, and P < .001, respectively). Compared with NIOMs, age, carbohydrate antigen 19 to 9, hemoglobin, calcium, total cholesterol, low-density lipoprotein (LDL) and apolipoprotein A1 were remarkably lower in IOMs (P = .038, P < .001, P < .001, P = .032, P = .041, P < .001, and P = .001, respectively). Poisson regression suggested that CA-125, CA15-3 and LDL were contributing to IOMs in PBC as risk factors (OR = 1.003, 95% CI: 1.001-1.005; OR = 1.025, 95% CI: 1.019-1.033; OR = 0.238, 95% CI: 0.112-0.505, respectively). A receiver operating characteristic curve revealed that the cut-off values for CA-125, CA15-3 and LDL were 16.78 0 U/mL, 63.175 U/mL, and 2.415 mmol/L, respectively. The combination of CA-125 and CA15-3 showed significant diagnostic value (area under the curve [AUC] = 0.982, P < .001). Our investigation suggests that CA-125, CA15-3 and LDL remarkably predict IOMs in PBC as risk factors, and the combination of CA-125 and CA15-3 shows considerable diagnostic value.
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http://dx.doi.org/10.1097/MD.0000000000027693DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556018PMC
October 2021

Erzhi pills ameliorate cognitive dysfunction and alter proteomic hippocampus profiles induced by d-galactose and Aβ injection in ovariectomized Alzheimer's disease model rats.

Pharm Biol 2021 Dec;59(1):1402-1414

School of Pharmacy, Jiangxi University of Chinese Medicine, Nanchang, China.

Context: Erzhi pills are a classic Chinese medicine prescription, but their effects on Alzheimer's disease (AD) are not clear.

Objective: The protective effects of Erzhi pills in AD rats and their potential mechanisms were investigated.

Materials And Methods: An AD rat model was established by ovariectomy combined with d-galactose and Aβ injection. Rats were randomly divided into five groups: sham-operated, model, oestradiol valerate (0.80 mg/kg), Erzhi pills high-dose (1.50 g/kg), and Erzhi pills low-dose (0.75 g/kg). Learning and memory abilities were evaluated with the Morris water maze test, oestrogen levels with an ELISA kit, and hippocampal neuron morphology and Nissl bodies in the cytoplasm with H&E and Nissl staining. The expression of ERβ, Aβ, and p-tau was determined by immunohistochemistry. Nano LC-LTQ-Orbitrap Proteomics determined potential targets and related signalling pathways. Western blotting was used to detect the expression of the related proteins.

Results: Erzhi pills (1.5, 0.75 g/kg) markedly reduced escape latencies on the MWM, increased numbers of platform crossings, numbers of neurons, Nissl bodies, oestrogen levels (100.18, 43.04 pg/mL), and ERβ-positive cells (57.42, 39.83); Aβ (18.85, 36.83)- and p-tau (14.42, 29.71)-positive cells were significantly decreased. Proteomics identified more than 100 differentially expressed proteins involved in 48 signalling pathways, five of which are involved in the PI3K/Akt signalling pathway. Western blotting showed decreased expression of GSK3β and Bad, while Akt, PI3K, 14-3-3, Bcl-xl, and Bcl-2 were upregulated.

Discussion And Conclusion: Erzhi pills may serve as a potential agent for AD therapeutics by improving learning and memory.
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http://dx.doi.org/10.1080/13880209.2021.1990353DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8547838PMC
December 2021

Serum sCD14 as a Biomarker for Significant Liver Inflammation in Chronic Hepatitis B Patients with Normal or Mildly Elevated ALT.

Clin Lab 2021 Oct;67(10)

Background: CD14 is a pattern recognition receptor constitutively expressed in different types of immune cells, either in a membrane-anchored (mCD14) or in a soluble (sCD14) form. This study investigated whether hepatic CD14 expression levels were correlated with the grades of liver inflammation as well as the potential usefulness of serum sCD14 as a biomarker for predicting liver inflammation in chronic hepatitis B (CHB) patients with normal or mildly elevated ALT.

Methods: A total of 216 treatment-naive CHB patients with normal or mildly elevated ALT who underwent liver biopsy were recruited. Hepatic expression level of CD14 was measured using immunohistochemistry and real-time PCR. Serum sCD14 concentrations were determined with an enzyme-linked immunosorbent assay. Correlations between hepatic CD14, serum sCD14, and liver inflammation grade were analyzed. Univariate and multivariate analysis were performed to identify significant liver inflammation-associated factors. The receiver operating characteristic curve was used to assess the discriminating power of serum sCD14 to significant liver inflammation in CHB patients with normal or mildly elevated ALT.

Results: Both hepatic expression levels of CD14 and serum sCD14 concentrations significantly increased with the aggravation of liver inflammation. Moreover, hepatic expression levels of CD14, serum sCD14 concentrations, and liver inflammation grades were positively correlated with each other. Three parameters including alkaline phosphatase (ALP), neutrophil, and sCD14 were identified as independent predictors of significant liver inflammation. Subsequently, a diagnostic equation named model-sCD14 was developed incorporating sCD14 and other variables (ALP and neutrophils) with p < 0.05 in multivariate logistic analysis. The area under receiver operating characteristic curve (AUC) of sCD14 for predicting significant liver inflammation was 0.788 and the optimal cutoff was 27.14 ng/mL, with a sensitivity of 66.67%, a specificity of 81.70%, positive predictive value of 60.01%, and negative predictive value of 85.62%. When sCD14 was replaced by model-sCD14, the AUC value increased from 0.788 to 0.843 (z = 2.311, p = 0.021), with sensitivity of 77.78%, specificity of 77.12%, positive predictive value of 58.33%, and negative predictive value of 89.39%.

Conclusions: Serum sCD4 has the potential to discriminate significant liver inflammation from CHB patients with normal or mildly increased ALT levels.
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http://dx.doi.org/10.7754/Clin.Lab.2021.210130DOI Listing
October 2021

Whole-Exome Sequencing on Circulating Tumor Cells Explores Platinum-Drug Resistance Mutations in Advanced Non-small Cell Lung Cancer.

Front Genet 2021 20;12:722078. Epub 2021 Sep 20.

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Circulating tumor cells (CTCs) have important applications in clinical practice on early tumor diagnosis, prognostic prediction, and treatment evaluation. Platinum-based chemotherapy is a fundamental treatment for non-small cell lung cancer (NSCLC) patients who are not suitable for targeted drug therapies. However, most patients progressed after a period of treatment. Therefore, revealing the genetic information contributing to drug resistance and tumor metastasis in CTCs is valuable for treatment adjustment. In this study, we enrolled nine NSCLC patients with platinum-based chemotherapy resistance. For each patient, 10 CTCs were isolated when progression occurred to perform single cell-level whole-exome sequencing (WES). Meanwhile the patients' paired primary-diagnosed formalin-fixed and paraffin-embedded samples and progressive biopsy specimens were also selected to perform WES. Comparisons of distinct mutation profiles between primary and progressive specimens as well as CTCs reflected different evolutionary mechanisms between CTC and lymph node metastasis, embodied in a higher proportion of mutations in CTCs shared with paired progressive lung tumor and hydrothorax specimens (4.4-33.3%) than with progressive lymphatic node samples (0.6-11.8%). Functional annotation showed that CTCs not only harbored cancer-driver gene mutations, including frequent mutations of and shared with primary and/or progressive tumors, but also particularly harbored cell cycle-regulated or stem cell-related gene mutations, including , , , , , , , etc., most of which derived from primary tumor samples and played crucial roles in chemo-drug resistance and metastasis for NSCLCs. Thus, detection of genetic information in CTCs is a feasible strategy for studying drug resistance and discovering new drug targets when progressive tumor specimens were unavailable.
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http://dx.doi.org/10.3389/fgene.2021.722078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488217PMC
September 2021

Signal-enhanced and bi-directional interferometric Rayleigh scattering velocimetry using an asymmetry cavity.

Opt Express 2021 Aug;29(17):26701-26712

Interferometric Rayleigh scattering technique is commonly employed to measure single-point velocity fluctuation and its standard deviation in a high-speed flow due to many benefits, such as high accuracy, easy data interpretation, and high sampling rate. However, this technique suffers from a severe problem often referred to as the weak Rayleigh scattering signal, especially in the supersonic and hypersonic flow with an extremely low gas molecule density. An asymmetry cavity structure that could cost-effectively improve the Rayleigh scattering (RS) signal of interest is designed and used in the interferemetric Rayleigh scattering technique. The ZEMAX simulations suggest that the parallel beam can be repeatedly reflected in the resonant cavity and can be focused in a measurement region with the order of 0.67 mm×1.31 mm. The number of propagating rays inside the cavity can reach about 50. The fidelity of this proposed cavity is then verified by the Rayleigh scattering imaging experiments. Results show that this cavity allows the laser beam to reflect several times in the resonant cavity, and the RS signal intensity in the major axis can be 10.4 times larger than that of the incident laser. The cavity is finally employed under realistic supersonic flow velocity measurements, where the results conclusively illustrate that the Rayleigh scattering signal of interest in a single direction can be improved by a factor of 4∼5. In addition, the bi-directional (both the axial and radial directions) velocity parameters can also be obtained simultaneously. The axial velocity and its standard deviation are similar to conventional single-line ones.
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http://dx.doi.org/10.1364/OE.433316DOI Listing
August 2021

ctDNA-Profiling-Based UBL Biological Process Mutation Status as a Predictor of Atezolizumab Response Among -Negative NSCLC Patients.

Front Genet 2021 7;12:723670. Epub 2021 Sep 7.

Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

Atezolizumab, an immune checkpoint inhibitor, has been approved for use in clinical practice in non-small cell lung cancer (NSCLC) patients, but potential biomarkers for response stratification still need further screening. In the present study, a total of 399 patients with high-quality ctDNA profiling results were included. The mutation status of ubiquitin-like conjugation (UBL) biological process genes (including , , , , , and ) and clinical information were further integrated. The results suggested that the patients with the clinical characteristics of male or history of smoking had a higher frequency of UBL mutation positivity [UBL (+)]; the patients who were UBL (+) had shorter progression-free survival (PFS) (1.69 vs. 3.22 months, = 0.0007) and overall survival (8.61 vs. 16.10 months, < 0.0001) than those patients with UBL mutation negativity [UBL (-)]; and more promising predictive values were shown in the smoker subgroup and ≤ 3 metastasis subgroup. More interestingly, we found the predictor has more performance in -negative cohorts [training in an independent POPLAR and OAK cohorts ( = 200), and validation in an independent MSKCC cohort ( = 127)]. Overall, this study provides a predictor, UBL biological process gene mutation status, not only for identifying NSCLC patients who may respond to atezolizumab therapy but also for screening out the potential NSCLC responders who received other immune checkpoint inhibitors.
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http://dx.doi.org/10.3389/fgene.2021.723670DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8452871PMC
September 2021

Evidence-based complementary and alternative medicine bioinformatics approach through network pharmacology and molecular docking to determine the molecular mechanisms of Erjing pill in Alzheimer's disease.

Exp Ther Med 2021 Nov 2;22(5):1252. Epub 2021 Sep 2.

Department of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, Jiangxi 330004, P.R. China.

Erjing pill, a Traditional Chinese Medicine (TCM) formulation composed of and , has an important role in the treatment of Alzheimer's disease (AD). However, the underlying mechanisms of the action of Erjing pill in AD have remained elusive. In the present study, the key ingredients of Erjing pill were investigated and the active components and their mechanisms of action on AD were analyzed based on networks pharmacology. By using the TCM and TCM Systems Pharmacology and databases, the components of Erjing pill were screened and the data were captured using Discovery Studio. The SwissTarget webserver database was used to predict the potential protein targets of Erjing pill components for pathologies related to AD. The data were further analyzed with the disease targets of AD based on analysis of the Online Mendelian Inheritance in Man, DiGSeE and Therapeutic Target Database. Subsequent analysis of mechanistic pathways of the screened components and protein targets allowed us to construct a network by using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, which revealed potential molecular mechanisms of Erjing pill against AD. Finally, the protective effect of three active components on neurons was verified using an injury model of PC12 cells induced by Aβ. The results indicated that 65 bioactive components of Erjing pill, including lauric acid and zederone, and 6 targets, including acetylcholinesterase, butylcholinesterase and amyloid protein precursor, were closely associated with the prevention and treatment of AD. The molecular components of Erjing pill were indicated to be involved in various biological signaling processes, mainly in synaptic signal transmission, transsynaptic signal transmission and chemical synaptic transmission. Furthermore, related pathways targeted by Erjing pill in AD included the regulation of neuroactive ligand-receptor interactions, the PI3K-Akt signaling pathway, serotoninergic synapses, calcium signaling pathways and dopaminergic synapses. A cell viability assay indicated that the compounds (polygonatine A, polygonatine C and 4',5-dihydroxyflavone) assessed were able to significantly improve the survival rate and increase the Ca level in a PC12 cell model of AD induced by amyloid-β. The present study revealed that the mechanisms of action of Erjing pill to prevent and treat AD included a multicompound, multitarget and multipathway regulatory network.
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http://dx.doi.org/10.3892/etm.2021.10687DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8438686PMC
November 2021

Dietary Seleno-l-Methionine Causes Alterations in Neurotransmitters, Ultrastructure of the Brain, and Behaviors in Zebrafish ().

Environ Sci Technol 2021 09 15;55(17):11894-11905. Epub 2021 Aug 15.

SCNU Environmental Research Institute, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, China.

Elevated concentrations of dietary selenium (Se) cause abnormalities and extirpation of fish inhabiting in Se-contaminated environments. However, its effect on fish behavior and the underlying mechanisms remain largely unknown. In this study, two-month-old zebrafish () was fed seleno-l-methionine (Se-Met) at environmentally relevant concentrations (i.e., control (2.61), low (5.43), medium (12.16), and high (34.61) μg Se/g dry weight (dw), respectively, corresponding to the C, L, M, and H treatments) for 60 days. Targeted metabolomics, histopathological, and targeted transcriptional endpoints were compared to behavioral metrics to evaluate the effects of dietary exposure to Se-Met . The results showed that the levels of total Se and malondialdehyde in fish brains were increased in a dose-dependent pattern. Meanwhile, mitochondrial damages and decreased activities of the mitochondria respiratory chain complexes were observed in the neurons at the M and H treatments. In addition, dietary Se-Met affected neurotransmitters, metabolites, and transcripts of the genes associated with the dopamine, serotonin, gamma-aminobutyric acid, acetylcholine, and histamine signaling pathways in zebrafish brains at the H treatments. The total swimming distance and duration in the Novel Arm were lowered in fish from the H treatment. This study has demonstrated that dietary Se-Met affects the ultrastructure of the zebrafish brain, neurotransmitters, and associated fish behaviors and may help enhance adverse outcome pathways for neurotransmitter-behavior key events in zebrafish.
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http://dx.doi.org/10.1021/acs.est.1c03457DOI Listing
September 2021

Parameter estimation for a damped real-valued sinusoid in noise.

Rev Sci Instrum 2021 Aug;92(8):085103

Faculty of Mechanical Engineering and Automation, Zhejiang Sci-Tech University, Hangzhou 310018, People's Republic of China.

In this paper, a three-point interpolation algorithm based on the discrete Fourier transform (DFT) is presented for a damped real-valued sinusoid, and the algorithm considers comprehensively the contribution of negative frequency to the parameter estimation (including that of the frequency and the damping factor). The proposed algorithm uses the DFT spectral bin with the maximum amplitude and two other arbitrary ones within the main lobe of the spectrum of the rectangular window to remove the negative-frequency interference completely. First, the effect of changed length of samples on the performance of the proposed algorithm is investigated, and the influence of the zero-padding technique and the selection of two arbitrary spectral bins on the ratio of the mean-square error (MSE) to the Crámer-Rao lower bound are also analyzed by simulations. Second, the MSEs of the estimated parameters are calculated to evaluate the performances of the proposed algorithm and state-of-the-art DFT-based algorithms in the literature. Third, the computational complexities of the proposed and comparative algorithms are analyzed. The results confirm the effectiveness of the proposed algorithm.
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http://dx.doi.org/10.1063/5.0049885DOI Listing
August 2021

Pain relief and cartilage repair by Nanofat against osteoarthritis: preclinical and clinical evidence.

Stem Cell Res Ther 2021 08 26;12(1):477. Epub 2021 Aug 26.

The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, 310053, Zhejiang, People's Republic of China.

Background: Osteoarthritis (OA) is the most common joint degenerative disorder, with little effective therapy to date. Nanofat is a cocktail of cells obtained from fat tissue, which possesses regenerative capacity and has a potential in treating OA. This study aimed to determine the anti-OA efficacy of Nanofat from basic and clinical aspects and explore its action mode.

Methods: Flow cytometry was performed to characterize Nanofat. A monoiodoacetate-induced OA rat model was employed for in vivo study. Cell viability and wound healing assays were conducted for in vitro study. Real-time PCR and Western blot assays were applied to explore the molecular action mode of Nanofat. Moreover, a retrospective analysis was conducted to determine the clinical efficacy and safety of Nanofat on knee OA patients.

Results: The in vivo results showed that Nanofat significantly attenuated pain symptoms and protected cartilage ECM (Col2) from damage, and its effects were not significantly differed with adipose tissue-derived stem cells (both P > 0.05). The in vitro results showed that Nanofat promoted the cell viability and migration of chondrocytes and significantly restored the IL-1β-induced abnormal gene expressions of Col2, Aggrecan, Sox9, Adamts5, Mmp3, Mmp9 Mmp13, IL-6 and Col10 and protein expressions of Col2, MMP9, MMP13, and Sox9 of chondrocytes. The regulatory actions of Nanofat on these anabolic, catabolic, and hypertrophic molecules of chondrocytes were similar between two treatment routes: co-culture and conditioned medium, suggesting a paracrine-based mode of action of Nanofat. Moreover, the clinical data showed that Nanofat relieved pain and repaired damaged cartilage of OA patients, with no adverse events.

Conclusion: In sum, this study demonstrated the anti-OA efficacy as well as a paracrine-based action mode of Nanofat, providing novel knowledge of Nanofat and suggesting it as a promising and practical cell therapy for clinical treatment of OA.
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http://dx.doi.org/10.1186/s13287-021-02538-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8390235PMC
August 2021

Active Electromagnetically Induced Transparency Effect in Graphene-Dielectric Hybrid Metamaterial and Its High-Performance Sensor Application.

Nanomaterials (Basel) 2021 Aug 10;11(8). Epub 2021 Aug 10.

Collaborative Innovation Center for Bio-Med Physics Information Technology of ZJUT, Zhejiang University of Technology, Hangzhou 310023, China.

Electromagnetically induced transparency (EIT) based on dielectric metamaterials has attracted attentions in recent years because of its functional manipulation of electromagnetic waves and high refractive index sensitivity, such as high transmission, sharp phase change, and large group delay, etc. In this paper, an active controlled EIT effect based on a graphene-dielectric hybrid metamaterial is proposed in the near infrared region. By changing the Fermi level of the top-covered graphene, a dynamic EIT effect with a high quality factor (Q-factor) is realized, which exhibits a tunable, slow, light performance with a maximum group index of 2500. Another intriguing characteristic of the EIT effect is its high refractive index sensitivity. In the graphene-covered metamaterial, the refractive index sensitivity is simulated as high as 411 nm/RIU and the figure-of-merit (FOM) is up to 159, which outperforms the metastructure without graphene. Therefore, the proposed graphene-covered dielectric metamaterial presents an active EIT effect in the near infrared region, which highlights its great application potential in deep optical switching, tunable slow light devices, and sensitive refractive index sensors, etc.
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http://dx.doi.org/10.3390/nano11082032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8400393PMC
August 2021

The Clinical Significance and Functional Role of miR-466 in Gastric Cancer Peritoneal Metastasis.

Mol Biotechnol 2021 Aug 25. Epub 2021 Aug 25.

Department of General Surgery, First Affiliated Hospital of Kunming Medical University, No. 295, Xichang Road, Kunming, 650000, Yunnan, China.

The prognosis of metastasis gastric cancer patients remains poor and the identification of novel molecular markers will improve the management of gastric cancer patients. The present study aimed to investigate the clinical significance and functional role of miR-466 in gastric cancer peritoneal metastasis. miR-466 expression was confirmed by RT-qPCR. The biological functions were examined by MTT assay, Transwell migration, and invasion assays. The Kaplan-Meier survival curve and multivariate Cox regression analysis were used to investigate the clinical role of miR-466. The logistic regression analysis was performed to reveal the risk factors associated with peritoneal metastasis. miR-466 expression was downregulated in gastric cancer cell lines, tumor tissues, and peritoneal metastasis tissues compared with respective controls. Increased miR-466 expression inhibited proliferation, migration, and invasion of gastric cancer cells. Besides, the lower expression of miR-466 in gastric cancer patients was associated with peritoneal dissemination. Furthermore, multivariate Cox proportional hazard regression analyses demonstrated miR-466 expression level as an independent predictor of prognosis of gastric cancer. The present study provides novel evidence for the clinical and biological significance of miR-466 expression as a possible biomarker for the prognosis and identifying patients with peritoneal metastasis, as well as a potential therapeutic target in patients with gastric cancer.
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http://dx.doi.org/10.1007/s12033-021-00382-zDOI Listing
August 2021

Rapid identification of methylase specificity (RIMS-seq) jointly identifies methylated motifs and generates shotgun sequencing of bacterial genomes.

Nucleic Acids Res 2021 Nov;49(19):e113

New England Biolabs, Inc. 240 County Road Ipswich, MA 01938, USA.

DNA methylation is widespread amongst eukaryotes and prokaryotes to modulate gene expression and confer viral resistance. 5-Methylcytosine (m5C) methylation has been described in genomes of a large fraction of bacterial species as part of restriction-modification systems, each composed of a methyltransferase and cognate restriction enzyme. Methylases are site-specific and target sequences vary across organisms. High-throughput methods, such as bisulfite-sequencing can identify m5C at base resolution but require specialized library preparations and single molecule, real-time (SMRT) sequencing usually misses m5C. Here, we present a new method called RIMS-seq (rapid identification of methylase specificity) to simultaneously sequence bacterial genomes and determine m5C methylase specificities using a simple experimental protocol that closely resembles the DNA-seq protocol for Illumina. Importantly, the resulting sequencing quality is identical to DNA-seq, enabling RIMS-seq to substitute standard sequencing of bacterial genomes. Applied to bacteria and synthetic mixed communities, RIMS-seq reveals new methylase specificities, supporting routine study of m5C methylation while sequencing new genomes.
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http://dx.doi.org/10.1093/nar/gkab705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8565308PMC
November 2021

Impact of dosing strategies on plasma concentrations of tenofovir: Implications in HIV pre-exposure prophylaxis in China.

J Infect Public Health 2021 Sep 31;14(9):1169-1173. Epub 2021 Jul 31.

Key Laboratory of Molecular Biology and Infectious Diseases, Chongqing Medical University, Chongqing 400016, China. Electronic address:

Background: Tenofovir disoproxil fumarate has been recommended for pre-exposure prophylaxis (PrEP) to prevent HIV infection. Several studies have shown short but potent intermittent PrEP could provide comparable protection to daily PrEP in men, suggesting such dosing strategy might be useful in Chinese as well. The objective of this study was to evaluate the impact of different dosing strategies on plasma concentrations of tenofovir.

Methods: An open label study in 40 Chinese healthy volunteers, randomized to receive the WHO-recommended dose of tenofovir (300mg) at four different dosing intervals: twice weekly for 4 weeks; once daily for 4 weeks with one missing dose in weeks 2-4; once daily for 4 weeks with two missing doses in weeks 2-4; and once every other day for 12 days. Plasma samples were collected at pre-dose, weekly trough and 24h post last dose and assayed using HPLC-UV.

Results: The tenofovir trough concentrations were below the lower limit of quantification with the twice weekly regimen. The trough concentrations (24h dosing interval) at the steady state were 51.7±12.1ng/ml and 53.5±13.8ng/ml (mean±SD) in the once daily groups. Missing doses, once or twice weekly, had no significant impact on trough concentrations. Prolongation of dosing interval to 48h resulted with concentrations at 24h and 48h (trough) of ∼40 and 20ng/ml, respectively.

Conclusions: Intermittent tenofovir regimens resulted with remarkably low plasma concentrations in Chinese participants. Missing doses did not affect trough concentrations significantly.
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http://dx.doi.org/10.1016/j.jiph.2021.07.018DOI Listing
September 2021

EGFR/EGFRvIII partly regulates the tumourigenesis of glioblastoma through the SOX9-GLUT3 axis.

Am J Transl Res 2021 15;13(6):6055-6065. Epub 2021 Jun 15.

Department of Neurosurgery, The Affiliated Hospital of Hainan Medical College Haikou 570102, Hainan, China.

EGFR/EGFR variant III (EGFRvIII) glioblastoma is seriously malignant, and the underlying mechanism remains unclear. In this study, EGFR and GLUT3 were found to be co-expressed in our collected tissues and associated with worse overall survival in glioblastoma via bioinformatics analysis. Functionally, and tests revealed that silencing GLUT3 substantially inhibited the viability of U87-EGFRvIII and LN229-EGFRvIII cells. Compared with wild-type U87 or LN229 cells, the expression level of SOX9 in U87-EGFRvIII or LN229-EGFRvIII cells (U87 and LN229 over-expressing EGFRvIII) was substantially increased. Chromatin immunoprecipitation and Dual-luciferase reporter assays revealed that SOX9 bound to the promoter of GLUT3 and promoted the expression of GLUT3. Collectively, our findings indicated that the EGFR/EGFRvIII-SOX9-GLUT3 axis mediated the tumourigenesis of glioblastoma and might be a potential target for glioblastoma therapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8290802PMC
June 2021

Comparative chloroplast genome analysis of Impatiens species (Balsaminaceae) in the karst area of China: insights into genome evolution and phylogenomic implications.

BMC Genomics 2021 Jul 24;22(1):571. Epub 2021 Jul 24.

College of Landscape Architecture and Horticulture Sciences, Southwest Research Center for Engineering Technology of Landscape Architecture(State Forestry and Grassland Administration), Yunnan Engineering Research Center for Functional Flower Resources and Industrialization, Research and Development Center of Landscape Plants and Horticulture Flowers, Southwest Forestry University, Kunming, Yunnan, 650224, China.

Background: Impatiens L. is a genus of complex taxonomy that belongs to the family Balsaminaceae (Ericales) and contains approximately 1000 species. The genus is well known for its economic, medicinal, ornamental, and horticultural value. However, knowledge about its germplasm identification, molecular phylogeny, and chloroplast genomics is limited, and taxonomic uncertainties still exist due to overlapping morphological features and insufficient genomic resources.

Results: We sequenced the chloroplast genomes of six different species (Impatiens chlorosepala, Impatiens fanjingshanica, Impatiens guizhouensis, Impatiens linearisepala, Impatiens loulanensis, and Impatiens stenosepala) in the karst area of China and compared them with those of six previously published Balsaminaceae species. We contrasted genomic features and repeat sequences, assessed sequence divergence and constructed phylogenetic relationships. Except for those of I. alpicola, I. pritzelii and I. glandulifera, the complete chloroplast genomes ranging in size from 151,366 bp (I. alpicola) to 154,189 bp (Hydrocera triflora) encoded 115 distinct genes [81 protein-coding, 30 transfer RNA (tRNA), and 4 ribosomal RNA (rRNA) genes]. Moreover, the characteristics of the long repeat sequences and simple sequence repeats (SSRs) were determined. psbK-psbI, trnT-GGU-psbD, rpl36-rps8, rpoB-trnC-GCA, trnK-UUU-rps16, trnQ-UUG, trnP-UGG-psaJ, trnT-UGU-trnL-UAA, and ycf4-cemA were identified as divergence hotspot regions and thus might be suitable for species identification and phylogenetic studies. Additionally, the phylogenetic relationships based on Maximum likelihood (ML) and Bayesian inference (BI) of the whole chloroplast genomes showed that the chloroplast genome structure of I. guizhouensis represents the ancestral state of the Balsaminaceae family.

Conclusion: Our study provided detailed information about nucleotide diversity hotspots and the types of repeats, which can be used to develop molecular markers applicable to Balsaminaceae species. We also reconstructed and analyzed the relationships of some Impatiens species and assessed their taxonomic statuses based on the complete chloroplast genomes. Together, the findings of the current study might provide valuable genomic resources for systematic evolution of the Balsaminaceae species.
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http://dx.doi.org/10.1186/s12864-021-07807-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8310579PMC
July 2021

The use of explainable artificial intelligence to explore types of fenestral otosclerosis misdiagnosed when using temporal bone high-resolution computed tomography.

Ann Transl Med 2021 Jun;9(12):969

School of Computer Science, Shanghai Key Laboratory of Intelligent Information Processing, Fudan University, Shanghai, China.

Background: The purpose of this study was to explore the common characteristics of fenestral otosclerosis (OS) which are misdiagnosed, and develop a deep learning model for the diagnosis of fenestral OS based on temporal bone high-resolution computed tomography scans.

Methods: We conducted a study to explicitly analyze the clinical performance of otolaryngologists in diagnosing fenestral OS and developed an explainable deep learning model using 134,574 temporal bone high-resolution computed tomography (HRCT) slices collected from 1,294 patients for the automatic diagnosis of fenestral OS. We prospectively created an external test set with 31,774 CT slices from 144 patients, which contained 86 fenestral OS ears and 202 normal ears and used it to evaluate the performance of our otosclerosis-Logical Neural Network (LNN) model to assess its potential clinical utility. In addition, we compared the diagnostic acumen of seven otolaryngologists with the otosclerosis-LNN approach in the clinical test set, which was mixed with 78 fenestral OS and 62 normal ears. Finally, to evaluate the assisting value of the model, the seven participants were again invited to classify all cases in the clinical test set after referring to the diagnostic results of the model, to which they were blinded.

Results: The diagnostic performance of otologists was not satisfactory, and those CT samples which were misdiagnosed had similar characteristics. Based on this finding, we defined three subtypes of fenestral OS lesions that are suitable for clinical diagnosis guidance: "focal", "transitional", and "typical" fenestral OS. The most encouraging result is that the model achieved an area under the curve (AUC) of 99.5% (per-ear-sensitivity of 96.4%, per-ear-specificity of 98.9%) on the prospective unknown external test. Furthermore, we used this model to assist otologists and observed a consistent and significant improvement in diagnostic performance, especially for the newly defined focal and transitional fenestral OS, which led to the initial high misdiagnosis rate.

Conclusions: Our findings of the fine-grained classification of fenestral OS could have implications for future diagnosis and prevention programs. In addition, our deep OS localization network is an effective approach providing assistance to otologists to deal with the significant challenge of the misdiagnosis of fenestral OS.
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http://dx.doi.org/10.21037/atm-21-1171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267294PMC
June 2021

Genetic Variants and Functional Analyses of the Gene Promoter in Acute Myocardial Infarction.

Front Genet 2021 17;12:591954. Epub 2021 Jun 17.

Shandong Provincial Key Laboratory of Cardiac Disease Diagnosis and Treatment, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, China.

Background: Acute myocardial infarction (AMI), a common complex disease caused by an interaction between genetic and environmental factors, is a serious type of coronary artery disease and is also a leading cause of death worldwide. Autophagy-related 16-like 1 () is a key regulatory factor of autophagy and plays an important role in induced autophagy. In the cardiovascular system, autophagy is essential to preserve the homeostasis and function of the heart and blood vessels. No studies have hitherto examined the association between AMI and gene promoter.

Methods: We conducted a case-control study, using polymerase chain reaction and sequencing techniques, dual luciferase reporter assay, and electrophoretic mobility shift assay, to analyze genetic and functional variation in the gene promoter between AMI and controls. A variety of statistical analyses were used to analyze the allele and genotype frequencies and the relationship between single-nucleotide polymorphisms (SNPs) and AMI.

Results: In all, 10 SNPs and two DNA-sequence variants (DSVs) were identified in 688 subjects, and three gene promoter mutations [g.233250693 T > C (rs185213911), g.233250946 G > A (rs568956599), g.233251133 C > G (rs1301744254)] that were identified in AMI patients significantly altered the transcriptional activity of gene promoter in HEH2, HEK-293, and H9c2 cells ( < 0.05). Further electrophoretic mobility shift assays indicated that the SNPs affected the binding of transcription factors ( < 0.01).

Conclusion: gene promoter mutations in AMI patients may affect the binding of transcription factors and change the transcriptional activity of the gene, changing the level of autophagy and contributing to the occurrence and development of AMI as rare and low-frequency risk factors.
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http://dx.doi.org/10.3389/fgene.2021.591954DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248370PMC
June 2021

Identification and functional study of GATA4 gene regulatory variants in atrial septal defects.

BMC Cardiovasc Disord 2021 06 30;21(1):321. Epub 2021 Jun 30.

Center for Molecular Genetics of Cardiovascular Diseases, Affiliated Hospital of Jining Medical University, Jining Medical University, Jining, 272100, Shandong, China.

Background: Congenital heart disease (CHD) is the leading cause of mortality from birth defects. In adult CHD patients with successful surgical repair, cardiac complications including heart failure develop at late stage, likely due to genetic causes. To date, many mutations in cardiac developmental genes have been associated with CHD. Recently, regulatory variants in genes have been linked to many human diseases. Although mutations and splicing variants in GATA4 gene have been reported in CHD patients, few regulatory variants of GATA4 gene are identified in CHD patients.

Methods: GATA4 gene regulatory region was investigated in the patients with atrial septal defects (ASD) (n = 332) and ethnic-matched controls (n = 336).

Results: Five heterozygous regulatory variants including four SNPs [g.31360 T>C (rs372004083), g.31436G>A, g.31437C>A (rs769262495), g.31487C>G (rs1053351749) and g.31856C>T (rs1385460518)] were only identified in ASD patients. Functional analysis indicated that the regulatory variants significantly affected the transcriptional activity of GATA4 gene promoter. Furthermore, two of the five regulatory variants have evidently effected on transcription factor binding sites.

Conclusions: Our data suggested that GATA4 gene regulatory variants may confer ASD susceptibility by decreasing GATA4 levels.
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http://dx.doi.org/10.1186/s12872-021-02136-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8243876PMC
June 2021

Neoadjuvant chemoimmunotherapy in resectable stage IIIA/IIIB non-small cell lung cancer.

Transl Lung Cancer Res 2021 May;10(5):2193-2204

Department of Lung Cancer, Tianjin Lung Cancer Center, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin, China.

Background: A small proportion of patients with non-small cell lung cancer (NSCLC) experience objective clinical benefit after neoadjuvant programmed cell death 1 (PD-1) blockade. A neoadjuvant therapeutic regimen combining immune checkpoint blockade with chemotherapy might improve the treatment effect, but such a regimen has not been tested in patients with resectable stage IIIA/IIIB NSCLC.

Methods: A retrospective study of 35 patients with resectable stage IIIA and IIIB NSCLC who were treated with neoadjuvant chemoimmunotherapy (NCIO) was performed. Patients were evaluated for pathological complete response (pCR), major pathologic response (MPR), safety, and feasibility. The correlations of pathologic response with various clinical factors were studied to identify predictors of pathological response.

Results: NCIO was associated with few immediate adverse events. NCIO did not delay planned surgery and led to a pCR rate of 51.43% and an MPR rate of 74.29% for the primary tumor. No association was observed between programmed death-ligand 1 (PD-L1) expression before NCIO and the pathologic response (Pearson's r=-0.071; P=0.685). However, a significant difference was observed in pathological response in patients with intracavitary and extracavitary tumors (P<0.05). Patients with intracavitary type had a higher pCR (76.47% 31.58%) and MPR (100% 50.00%) rate than patients with extracavitary type (Pearson's r=0.7280; P=0.0009).

Conclusions: NCIO was associated with few side effects, did not delay surgery, and achieved a pCR in 51.43% and MPR in 74.29% of resected tumors. No significant correlation was found between pathologic response and PD-L1 expression. While the intracavitary and extracavitary tumors type T was predictive of the pathological response to NCIO.
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http://dx.doi.org/10.21037/tlcr-21-329DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8182703PMC
May 2021

The protective effects of exogenous spermine on renal ischemia-reperfusion injury in rats.

Transl Androl Urol 2021 May;10(5):2051-2066

Department of Urology, Guizhou Provincial People's Hospital, Medical College of Guizhou University, Guiyang, China.

Background: To investigate the protective effects of exogenous spermine on renal ischemia-reperfusion injury in rats.

Methods: (I) Different doses of spermine were injected into rats to determine the safe dose on the kidneys. Kidney toxicity was assessed by hematoxylin and eosin (HE) staining of kidney tissue and enzyme-linked immunosorbent assay (ELISA) detection of neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule 1 (KIM-1) in the venous blood. (II) A rat model of renal ischemia-reperfusion injury was established. Different doses of spermine were injected into the rats through the tail vein 30 minutes before and 3 days after the establishment of the model. Blood samples and kidney tissues were collected and renal injury was assessed via HE staining of the renal tissue, detection of apoptosis using the TUNEL assay, and detection of NGAL and KIM-1 in blood samples using ELISA. (III) Human HK-2 renal tubular epithelial cells were cultured under hypoxia/reoxygenation conditions. To evaluate the protective effects of spermine, apoptosis was assessed by flow cytometry and TUNEL assay. The mechanisms underlying the effects of spermine were studied using Western blot analyses.

Results: At spermine concentrations below 200 µM (2 mL/kg body weight), no significant damage to the kidney was observed by HE staining, and there was no significant difference in NGAL and KIM-1 levels between rats treated with spermine and control rats (P<0.05). At spermine doses below 200 µM, HE staining showed that the degree of renal ischemia-reperfusion injury was gradually alleviated with increasing doses of spermine. TUNEL assays demonstrated that spermine reduced the apoptosis of renal tissue, and increasing doses of spermine gradually decreased the levels of NGAL and KIM-1 in the blood compared with the control group (P<0.05). Western blot analysis revealed that spermine increased the expression of pro-caspase9, phosphorylated protein kinase B (p-Akt), hypoxia-inducible factor 1 alpha (HIF-1α), B cell lymphoma 2 (Bcl-2), and Bcl2 interacting protein 3 (BNIP3), and decreased the expression of cleaved caspase-3, Bax and cytochrome C compared to control cells.

Conclusions: Exogenous spermine exerted a protective effect on renal ischemia-reperfusion injury in rats by inhibiting the apoptosis of renal tubular epithelial cells.
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http://dx.doi.org/10.21037/tau-21-280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8185668PMC
May 2021

[Eukaryotic expression and immunoactivity of protein A/G-horseradish peroxidase(PA/G-HRP) fusion protein as universal secondary antibody for detection of IgG originating from mice and rabbits].

Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi 2021 Jul;37(7):590-595

State Key Laboratory of Cancer Biology, Department of Immunology, Air Force Medical University, Xi'an 710032, China. *Corresponding authors, E-mail:

Objective To prepare universal secondary antibodies those can bind to the IgG from mice and rabbits, and use the antibodies in a variety of immunoassays. Methods The fusion genes of staphylococcal protein A (SPA), streptococcal protein G (SPG), and horseradish peroxidase (HRP) were synthesized, and cloned into the vector pcDNA3.1 to generate the eukaryotic expression plasmids. The plasmids were transiently transfected into HEK293F cells for expression. The fusion protein expressed in the plasmid was detected by SDS-PAGE and Western blotting, and its immunoactivity was measured by Western blotting, ELISA, and immunohistochemical staining. Results Restriction enzyme digestion and gene sequencing showed the pPA-HRP, pPG-HRP, and pPA/G-HRP plasmids were successfully created. Coomassie brilliant blue staining and Western blotting indicated that the fusion proteins PA-HRP, PG-HRP, and PA/G-HRP successfully expressed in HEK293F cells. Western blotting, ELISA, and immunohistochemical staining showed that IgGs derived from mice and rabbits could be recognized and bound by the three kinds of fusion protein, of which the fusion protein PA/G-HRP exhibited the highest affinity. Conclusion The fusion protein PA/G-HRP with high and universal IgG affinity is successfully prepared. The PA/G-HRP can replace traditional secondary antibodies against mouse and rabbit IgG in a variety of immunological assays.
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July 2021

Real-Time Pedestrian Tracking Terminal Based on Adaptive Zero Velocity Update.

Sensors (Basel) 2021 May 31;21(11). Epub 2021 May 31.

School of Information and Communication Engineering, University of Electronic Science and Technology of China, Chengdu 611731, China.

In the field of pedestrian dead reckoning (PDR), the zero velocity update (ZUPT) method with an inertial measurement unit (IMU) is a mature technology to calibrate dead reckoning. However, due to the complex walking modes of different individuals, it is essential and challenging to determine the ZUPT conditions, which has a direct and significant influence on the tracking accuracy. In this research, we adopted an adaptive zero velocity update (AZUPT) method based on convolution neural networks to classify the ZUPT conditions. The AZUPT model was robust regardless of the different motion types of various individuals. AZUPT was then implemented on the Zynq-7000 SoC platform to work in real time to validate its computational efficiency and performance superiority. Extensive real-world experiments were conducted by 60 different individuals in three different scenarios. It was demonstrated that the proposed system could work equally well in different environments, making it portable for PDR to be widely performed in various real-world situations.
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http://dx.doi.org/10.3390/s21113808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198276PMC
May 2021

Mechanical Properties and Toxicity Risks of Lead-Zinc Sulfide Tailing-Based Construction Materials.

Materials (Basel) 2021 May 29;14(11). Epub 2021 May 29.

College of Environmental Science and Engineering, Zhongkai University of Agriculture and Engineering, Guangzhou 510408, China.

The leaching residue of the lead-zinc sulfide tailing (LRT) is the only residue generated from the tailing leaching recovery process; it is a typical hazardous material for its high heavy-metal contents and high acidity. Due to the large output of LRT, and because its main components are Ca, Si, and Al, the preparation of building construction materials with LRT was studied. The results showed that when the LRT addition is less than 47%, with the ordinary Portland cement (OPC) and fly ash (FA) added and the curing conditions appropriate, the strength values of the tested specimens meet the M15 Class of the autoclaved lime sand brick standard (GB/T 16753-1997). The carbonization coefficient and drying shrinkage of the specimen were 0.79 and smaller than 0.42, respectively. As the SEM, TG, and XRD analysis have shown, the LRT can chemically react with additives to form stable minerals. The heavy metal contents that were leached out well met the limits in GB5085.3-2007. Based on the high addition of the LRT, the good strength and lower heavy metals were leached out of the prepared test specimen, and the tailing could be reused completely with the leaching recovery and the LRT reuse process. LRT can be used to replace OPC, allowing more sustainable concrete production and improved ecological properties of LRT.
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http://dx.doi.org/10.3390/ma14112940DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8198401PMC
May 2021

Contamination of drinking water by neonicotinoid insecticides in China: Human exposure potential through drinking water consumption and percutaneous penetration.

Environ Int 2021 11 24;156:106650. Epub 2021 May 24.

SCNU Environmental Research Institute, School of Environment, Guangdong Provincial Key Laboratory of Chemical Pollution and Environmental Safety & MOE Key Laboratory of Theoretical Chemistry of Environment, South China Normal University, Guangzhou 510006, PR China.

Neonicotinoids (NEOs) are the most widely used pesticides and have posed a serious threat to human health. However, data on human exposure to NEOs are extremely scarce. To bridge this gap, human exposure potential of NEOs through drinking water consumption and percutaneous penetration was evaluated with the influences of 17 age groups, 4 seasons, 6 regions, and 2 genders. The results showed that drinking water in the present study had an upper middle level of NEO contamination. Anthropogenic activity and weather condition played important roles in the regional distribution of NEOs in tap water. For both children and adults, NEOs intake from drinking water exposure (NDE) and percutaneous exposure (NPE) in the south regions of China are significantly higher than those in the north regions, while the order of NDE and NPE by season is summer > spring = autumn > winter. Furthermore, human age and gender also have remarkable impacts on NDE and NPE. The age groups of children subjected to the highest NDE and NPE were 9 months - 2 years old and 9-12 years old, respectively. This study provides insights into the role of seasonal and regional influence, age and gender in the risk of drinking water and percutaneous exposure to NEOs.
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http://dx.doi.org/10.1016/j.envint.2021.106650DOI Listing
November 2021
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