Publications by authors named "Dong Hu"

255 Publications

A suitable silicosis mouse model was constructed by repeated inhalation of silica dust via nose.

Toxicol Lett 2021 Oct 6;353:1-12. Epub 2021 Oct 6.

Key Laboratory of Industrial Dust Control and Occupational Health of the Ministry of Education, Anhui University of Science and Technology, China; Key Laboratory of Industrial Dust Deep Reduction and Occupational Health and Safety, Anhui University of Science and Technology of Anhui Higher Education Institutes, Anhui University of Science and Technology, China; School of Medicine, Department of Medical Frontier Experimental Center, Anhui University of Science and Technology, China; Anhui Province Engineering Laboratory of Occupational Health and Safety, Anhui University of Science and Technology, China; Cancer Institute, Fudan University Shanghai Cancer Center, Fudan University, Shanghai, China. Electronic address:

Silicosis as the serious occupational disease is highly necessary to construct a suitable mouse model for disclosing mechanism of occurrence and development in this disease. Here, the volume-effect relationship and volume-based survival curves in mice who inhaled silica suspension intranasally were analyzed. Notable, the optimal volume 80 μl repeated-inhalation by nose to silica suspension in the inbred mouse C57BL/6 J with the highest susceptibility to silicosis led to a great entrance into the lung and a high survival rate after instillation. After repeated-exposure to 20 mg/mL, 80 μl silica for 16 days and then fed without silica exposure until 31 days, weight of mice showed a trend of first decrease and then recover. Moreover, the degree of pulmonary inflammation and fibrosis in mice were analyzed by pathological and immunohistochemistry staining. Transforming growth factor-beta (TGF-β), smooth muscle alpha-actin (α-SMA) and collagen type-I (collagen I, Col-I) were significantly increased in the silica-exposed mouse lung at post-exposure day 16 compared with the controls. Sirius red stain and Micro-CT analysis showed that lung fibrosis formed at post-exposure day 31. This study highlights the critical importance of perfusion volume and repeated nasal drops in inducing inflammatory response and pulmonary fibrosis in silicosis.
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http://dx.doi.org/10.1016/j.toxlet.2021.09.014DOI Listing
October 2021

A comprehensive investigation of the microbial risk of secondary water supply systems in residential neighborhoods in a large city.

Water Res 2021 Sep 23;205:117690. Epub 2021 Sep 23.

College of the Environment & Ecology, Xiamen University, Xiamen 361102, China. Electronic address:

Secondary water supply systems (SWSSs) are characterized by long water stagnation and low levels of chlorine residuals, which may pose a high microbial risk to terminal users. In this study, the SWSSs of 12 residential neighborhoods in a metropolitan area of 5 million people in southeastern China were seasonally investigated to assess their microbial risks by determining more than 30 physicochemical and biological parameters. Although the microbiological quality of SWSS water met the requirements of the standards for drinking water quality of China, it did deteriorate in various aspects. The heterotrophic plate counts with R2A media were high (> 100 CFU/mL) in some SWSS tank and tap water samples. Propidium monoazide (PMA)-qPCR revealed a one magnitude higher abundance of viable bacteria in the tank and tap water samples (average 10 and 10 gene copies/mL, respectively) compared with the input water samples, and Enterococcus, Acanthamoeba, and Hartmannella vermiformis were only detected in the tanks. In particular, the high detection frequency of Legionella in 35% tank and 21% tap water samples suggested it is a supplementary microbial safety indicator in SWSSs. The microbial regrowth potential was more obvious in summer, and Illumina sequencing also demonstrated distinct seasonal changes in the relative abundance of bacterial gene sequences at the genus level. Turbidity and residual chlorine were closely connected with total bacterial biomass, and the latter seemed responsible for microbial community structure alteration. The extremely low chlorine residuals associated with a high abundance of total bacteria (as high as 10 gene copies/mL) and Legionella (as high as 10 gene copies/100 mL) in the closed valve tanks highlighted the high microbial risk increased by mishandling the operation of SWSSs. This study found that SWSSs possessed a higher microbial risk than the drinking water network, which suggested that the frequency and scope of monitoring the microbial risk of SWSSs in megacities should be strengthened for the purpose of waterborne epidemic disease prevention and control.
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http://dx.doi.org/10.1016/j.watres.2021.117690DOI Listing
September 2021

The Expression Profiles and Deregulation of UDP-Glycosyltransferase () Genes in Human Cancers and Their Association with Clinical Outcomes.

Cancers (Basel) 2021 Sep 6;13(17). Epub 2021 Sep 6.

Dicipline of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Bedford Park, SA 5042, Australia.

The human UDP-glycosyltransferase (UGTs) superfamily has 22 functional enzymes that play a critical role in the metabolism of small lipophilic compounds, including carcinogens, drugs, steroids, lipids, fatty acids, and bile acids. The expression profiles of genes in human cancers and their impact on cancer patient survival remains to be systematically investigated. In the present study, a comprehensive analysis of the RNAseq and clinical datasets of 9514 patients from 33 different TCGA (the Genome Cancer Atlas) cancers demonstrated cancer-specific UGT expression profiles with high interindividual variability among and within individual cancers. Notably, cancers derived from drug metabolizing tissues (liver, kidney, gut, pancreas) expressed the largest number of genes (COAD, KIRC, KIRP, LIHC, PAAD); six genes (, , , , , ) showed high expression in five or more different cancers. Kaplan-Meier plots and logrank tests revealed that six genes were significantly associated with increased overall survival (OS) rates [ (LUSC), (ACC), (ACC), (KIRC), (BLCA, SKCM)] or decreased OS rates [ (LGG), (UVM)] in specific cancers. Finally, differential expression analysis of 611 patients from 12 TCGA cancers identified 16 genes (, , , , , , , , , , , , , , , ) that were up/downregulated in at least one cancer relative to normal tissues. In conclusion, our data show widespread expression of genes in cancers, highlighting the capacity for intratumoural drug metabolism through the UGT conjugation pathway. The data also suggests the potentials for specific genes to serve as prognostic biomarkers or therapeutic targets in cancers.
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http://dx.doi.org/10.3390/cancers13174491DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430925PMC
September 2021

[Effects of multifunctional plant rhizosphere promoting bacteria on maize growth in black soil areas in Northeast China].

Ying Yong Sheng Tai Xue Bao 2020 Aug;31(8):2759-2766

College of Biological Sciences, China Agricultural University/Key Laboratory of Soil Microbiology, Ministry of Agriculture, Beijing 100193, China.

The application of microbial fertilizer plays an important role in improving soil restoration and fertilizer utilization. The effects of microbial fertilizer are greatly affected by crop genotypes and ecological conditions. Little is known about the effects of microbial fertilizers on maize production in Northeast China. To develop microbial fertilizer specific to the black soil and the climate characteristics of Northeast China, we isolated five plant rhizosphere-promoting bacteria (PGPR), named as MZ1, MZ2, MZ3, MZ4 and MZ5, with different degrees of biological functions such as IAA synthesis, phosphate-solubilizing, potassium-solubilizing and siderophore-releasing, from the rhizosphere of maize field. The analysis of ecological adaptability showed that those five strains differed in salt resistance, drought tolerance, acid and alkali resistance, pesticide resistance. The 16S rRNA gene sequences analysis showed that the strains MZ1, MZ2, MZ3, MZ4 and MZ5 belonged to the genus of and respectively. In maize field experiment with 50% nitrogen fertilizer reduction, the inoculation with MZ1, MZ3 and MZ5 increased grain yield by 19.9%-25.0%. MZ1, MZ3, and MZ5 could be used as microbial fertilizers for maize in Northeast China.
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http://dx.doi.org/10.13287/j.1001-9332.202008.036DOI Listing
August 2020

Four Simple Biomimetic Mineralization Methods to Improve the Thermostability and Immunogenicity of Virus-like Particles as a Vaccine against Foot-and-Mouth Disease.

Vaccines (Basel) 2021 Aug 12;9(8). Epub 2021 Aug 12.

State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730030, China.

The need for a cold chain system during storage and transport substantially increases the cost of vaccines. Virus-like particles (VLPs) are among the best countermeasures against foot and mouth disease virus (FMDV). However, VLPs are composed of pure proteins, and thus, are susceptible to heat. To address this problem, four simple biomimetic mineralization methods with the use of calcium phosphate were developed to improve heat tolerance via biomineralization. The results showed that biomineralization can significantly improve the heat resistance of VLPs. The biomineralized VLPs can be stored at low as 25 °C for eight days, and 37 °C for four days. Animal experiments showed that biomineralization had no effect on the immunogenicity of VLPs or the expression of specific antibodies (Abs) and neutralizing Abs. Even after heat treatment at 37 °C for four days, the biomineralized VLPs remained immunogenic and produced highly specific and neutralizing Abs with a high rate of protection. These results suggest that these biomineralization approaches can promote the thermal stability of VLPs against and significantly reduce dependence on cold storage and delivery systems.
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http://dx.doi.org/10.3390/vaccines9080891DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402440PMC
August 2021

[Effect of amino acid site modification on stability of foot-and-mouth disease virus-like particles].

Sheng Wu Gong Cheng Xue Bao 2021 Jul;37(7):2435-2442

National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, Gansu, China.

The stability of virus-like particles (VLPs) is currently the main factor affecting the quality of foot-and-mouth disease VLPs vaccines. In order to further improve the quality of the VLPs vaccine of foot-and-mouth disease (FMD), three amino acid modification sites were designed and screened through kinetic analysis software, based on the three-dimensional structure of FMDV. The three mutant recombinant plasmids were successfully prepared by the point mutation kit, transformed into Escherichia coli strain BL21 and expressed in vitro. After purification by Ni ion chromatography column, SDS-PAGE proved that the three amino acid mutations did not affect the expression of the target protein. The results of the stability study of three FMD mutant VLPs obtained by in vitro assembly show that the introduction of internal hydrophobic side chain amino acids made the morphology of VLPs more uniform (N4017W), and their stability was significantly improved compared to the other two VLPs. The internal hydrophobic force of the capsid contributes to the formation of VLPs and helps to maintain the stability of the capsid, providing new experimental ideas for improving the quality of VLPs vaccines, and helping to promote the development of VLPs vaccines.
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http://dx.doi.org/10.13345/j.cjb.200551DOI Listing
July 2021

Changes in telomere length and serum neurofilament light chain levels in female patients with chronic insomnia disorder.

J Clin Sleep Med 2021 Jul 28. Epub 2021 Jul 28.

Department of Neurology, The First Affiliated Hospital of Anhui University of Science and Technology (The First People's Hospital of Huainan City), Huainan, 2P. R. China.

Study Objectives: The aims of this study were to explore changes in the telomere length (relative telomere repeat copy/single-copy gene, T/S ratio) and serum neurofilament light chain (sNfL) levels in female patients with chronic insomnia disorder (CID), examine their relationships with emotional abnormalities and cognitive impairment, and determine whether these 2 indicators were independently associated with sleep quality.

Methods: The CID group contained 80 patients diagnosed with CID, and 51 individuals constituted a healthy control group (HC). Participants completed sleep, emotion, and cognition assessments. Telomere length was detected through quantitative real-time polymerase chain reaction (qRT-PCR). Enzyme-linked immunosorbent assay was used to determine sNfL concentrations.

Results: Relative to the HC group, the CID group had elevated Pittsburgh Sleep Quality Index (PSQI), Hamilton Anxiety scale-14 (HAMA-14), and Hamilton Depression Rating scale-17 (HAMD-17) scores and reduced Montreal Cognitive Assessment scale (MoCA) scores, a decreased T/S ratio, and an increased sNfL concentration. Subgroup analysis according to various CID-associated sleep factors showed that poor sleep performance corresponded with a lower T/S ratio. Higher anxiety levels and more cognitive dysfunction correlated with shorter telomere lengths. The T/S ratio negatively correlated with age, whereas the sNfL concentration positively correlated with age in the CID group. The PSQI score negatively correlated with the T/S ratio but did not correlate with sNfL levels. Multiple linear regression analysis showed that the T/S ratio had a negative and independent effect on PSQI scores.

Conclusions: The CID group had shorter telomeres and higher sNfL concentrations, and reduced telomere length independently affected sleep quality.
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http://dx.doi.org/10.5664/jcsm.9574DOI Listing
July 2021

Whole-exome sequencing reveals genetic risks of early-onset sporadic dilated cardiomyopathy in the Chinese Han population.

Sci China Life Sci 2021 Jul 22. Epub 2021 Jul 22.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

To reveal genetic risks of early-onset sporadic dilated cardiomyopathy (DCM) patients in the Chinese Han population, we enlisted 363 DCM cases and 414 healthy controls. Whole-exome sequencing and phenotypic characterization were conducted. In total, we identified 26 loss-of-function (LOF) candidates and 66 pathogenic variants from 33 genes, most of which were novel. The deleterious variants can account for 25.07% (91/363) of all patients. Furthermore, rare missense variants in 21 genes were found to be significantly associated with DCM in burden tests. Other than rare variants, twelve common SNPs were significantly associated with an increased risk of DCM in allele-based genetic model association analysis. Of note, in the cumulative risk model, high-risk subjects had a 3.113-fold higher risk of developing DCM than low-risk subjects. Also, DCM in the high-risk group had a younger age of onset than that in the low-risk group. In terms of cardiac function, the mean left ventricular ejection fraction of patients with the deleterious variants was lower than those without (27.73%±10.02% vs. 30.61%±10.85%, P=0.026). To conclude, we mapped a comprehensive atlas of genetic risks in Chinese patients with DCM that might lead to new insights into the mechanisms and risk stratification for DCM.
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http://dx.doi.org/10.1007/s11427-020-1951-4DOI Listing
July 2021

Construction and Verification of a Radiation Pneumonia Prediction Model Based on Multiple Parameters.

Cancer Control 2021 Jan-Dec;28:10732748211026671

School of Medicine, Anhui University of Science and Technology, Huainan, People's Republic of China.

Objective: Patients with lung cancer are at risk of radiation pneumonia (RP) after receiving radiotherapy. We established a prediction model according to the critical indicators extracted from radiation pneumonia patients.

Materials And Methods: 74 radiation pneumonia patients were involved in the training set. Firstly, the clinical data, hematological and radiation dose parameters of the 74 patients were screened by Logistics regression univariate analysis according to the level of radiation pneumonia. Next, Stepwise regression analysis was utilized to construct the regression model. Then, the influence of continuous variables on RP was tested by smoothing function. Finally, the model was externally verified by 30 patients in validation set and visualized by R code.

Results: In the training set, there was 40 patients suffered≥ level 2 acute radiation pneumonia. Clinical data (diabetes), blood indexes (lymphocyte percentage, basophil percentage, platelet count) and radiation dose (V15 > 40%, V20 > 30%, V35 >18%, V40 > 15%) were related to radiation pneumonia ( < 0.05). Particularly, stepwise regression analysis indicated that the history of diabetes, the basophils percentage, platelet count and V20 could be the best combination used for predicting radiation pneumonia. The column chart was obtained by fitting the regression model with the combined indicator. The receiver operating characteristic (ROC) curve showed that the AUC in the development term was 0.853, the AUC was 0.656 in the validation term. And calibration curves of both groups showed the high stability in efficiently diagnostic. Furthermore, the DCA curve showed that the model had a satisfactory positive net benefit.

Conclusion: The combination of the basophils percentage, platelet count and V20 is available to build a predictive model of radiation pneumonia for patients with advanced lung cancer.
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http://dx.doi.org/10.1177/10732748211026671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8287426PMC
July 2021

Clinical characteristics, risk factors, and cardiac manifestations of cancer patients with COVID-19.

J Appl Physiol (1985) 2021 09 8;131(3):966-976. Epub 2021 Jul 8.

Department of Cardiology and Cardiovascular Research Institute, Renmin Hospital of Wuhan University, Wuhan, Hubei, China.

Coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been associated with cardiovascular features, which may be deteriorated in patients with cancer. However, cardiac outcomes of cancer patients with COVID-19 have not been closely examined. We retrospectively assessed 1,244 patients with COVID-19 from February 1 to August 31, 2020 (140 cancer and 1,104 noncancer patients). Demographic and clinical data were obtained and compared between cancer and noncancer groups. Including the cardiac biomarkers, we also analyzed laboratory findings between these two groups. Risk factors for in-hospital mortality were identified by multivariable Cox regression models. For cancer group, 56% were in severe and critical status with more diabetes and immune deficiency, whereas the proportion was 10% for noncancer group. Patients with cancer had increased levels of leukocyte, neutrophil count, and blood urea nitrogen (BUN) (all < 0.01), whereas lymphocyte count was significantly lower ( < 0.001). The most common solid tumor types were gastrointestinal cancer (26%), lung cancer (21%), and breast and reproductive cancer (both 19%). There is a rising for cardiac biomarkers, including pro-B-type natriuretic peptide (Pro-BNP), sensitive troponin I (cTnI), myoglobin (MYO), creatine kinase-MB (CK-MB), as well as D-Dimer in COVID-19 cancer population, especially in deceased subjects with cancer. The 30-day in-hospital mortality in cancer group was dramatically raised than that in noncancer group (12.9% vs. 4.0%, < 0.01). In multivariable Cox regression models, fever, disease severity status, and underlying diseases were risk factors for mortality. COVID-19 patients with cancer relate to deteriorating conditions and poor cardiac outcomes accompanied by a high in-hospital mortality, which warrants more aggressive treatment. Our study indicates that the 30-day mortality is higher in COVID-19 patients with cancer; more COVID-19 patients with cancer are in severe and critical status; age, respiratory rate, neutrophil count, AST, BUN, MYO, Pro-BNP, disease severity status, underlying diseases, and fever are risk factors for in-hospital mortality among COVID-19 cancer cases; COVID-19 patients with cancer display severely impaired myocardium, damaged heart function, and imbalanced homeostasis of coagulation; what is more, those with both cancer and CVD have more significantly increased Pro-BNP and D-Dimer level.
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http://dx.doi.org/10.1152/japplphysiol.00325.2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8422422PMC
September 2021

Identification of COL3A1 variants associated with sporadic thoracic aortic dissection: a case-control study.

Front Med 2021 Jun 28;15(3):438-447. Epub 2021 May 28.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Thoracic aortic dissection (TAD) without familial clustering or syndromic features is known as sporadic TAD (STAD). So far, the genetic basis of STAD remains unknown. Whole exome sequencing was performed in 223 STAD patients and 414 healthy controls from the Chinese Han population (N = 637). After population structure and genetic relationship and ancestry analyses, we used the optimal sequence kernel association test to identify the candidate genes or variants of STAD. We found that COL3A1 was significantly relevant to STAD (P = 7.35 × 10) after 10 000 times permutation test (P = 2.49 × 10). Moreover, another independent cohort, including 423 cases and 734 non-STAD subjects (N = 1157), replicated our results (P = 0.021). Further bioinformatics analysis showed that COL3A1 was highly expressed in dissected aortic tissues, and its expression was related to the extracellular matrix (ECM) pathway. Our study identified a profile of known heritable TAD genes in the Chinese STAD population and found that COL3A1 could increase the risk of STAD through the ECM pathway. We wanted to expand the knowledge of the genetic basis and pathology of STAD, which may further help in providing better genetic counseling to the patients.
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http://dx.doi.org/10.1007/s11684-020-0826-1DOI Listing
June 2021

Erratum: Exosomes released by human umbilical cord mesenchymal stem cells protect against renal interstitial fibrosis through ROS-mediated P38MAPK/ERK signaling pathway.

Am J Transl Res 2021 15;13(4):3921-3922. Epub 2021 Apr 15.

Department of Urology, Children's Hospital of Chongqing Medical University Chongqing 400014, China.

[This corrects the article on p. 4998 in vol. 12, PMID: 33042402.].
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129282PMC
April 2021

A Heat-Induced Mutation on VP1 of Foot-and-Mouth Disease Virus Serotype O Enhanced Capsid Stability and Immunogenicity.

J Virol 2021 07 26;95(16):e0017721. Epub 2021 Jul 26.

State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.

Foot-and-mouth disease (FMD) is a highly contagious viral disease affecting cloven-hoofed animals that causes a significant economic burden globally. Vaccination is the most effective FMD control strategy. However, FMD virus (FMDV) particles are prone to dissociate when appropriate physical or chemical conditions are unavailable, such as an incomplete cold chain. Such degraded vaccines result in compromised herd vaccination. Therefore, thermostable FMD particles are needed for use in vaccines. This study generated thermostable FMDV mutants (M3 and M10) by serial passages at high temperature, subsequent amplification, and purification. Both mutants contained an alanine-to-threonine mutation at position 13 in VP1 (A1013T), although M3 contained 3 additional mutations. The selected mutants showed improved stability and immunogenicity in neutralizing antibody titers, compared with the wild-type (wt) virus. The sequencing analysis and cryo-electron microscopy showed that the mutation of alanine to threonine at the 13th amino acid in the VP1 protein (A1013T) is critical for the capsid stability of FMDV. Virus-like particles containing A1013T (VLP) also showed significantly improved stability to heat treatment. This study demonstrated that Thr at the 13th amino acid of VP1 could stabilize the capsid of FMDV. Our findings will facilitate the development of a stable vaccine against FMDV serotype O. Foot-and-mouth disease (FMD) serotype O is one of the global epidemic serotypes and causes significant economic loss. Vaccination plays a key role in the prevention and control of FMD. However, the success of vaccination mainly depends on the quality of the vaccine. Here, the thermostable FMD virus (FMDV) mutants (M3 and M10) were selected through thermal screening at high temperatures with improved stability and immunogenicity compared with the wild-type virus. The results of multisequence alignment and cryo-electron microscopy (cryo-EM) analysis showed that the Thr substitution at the 13th amino acid in the VP1 protein is critical for the capsid stability of FMDV. For thermolabile type O FMDV, this major discovery will aid the development of its thermostable vaccine.
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http://dx.doi.org/10.1128/JVI.00177-21DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8312871PMC
July 2021

Clinical Significance of Variants in the Gene in a Large Cohort of Patients With Sporadic Dilated Cardiomyopathy.

Front Cardiovasc Med 2021 30;8:657689. Epub 2021 Apr 30.

Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Mutations in the gene are the most common causes of dilated cardiomyopathy (DCM). The clinical significance of gene variants remains inadequately understood. Whole-exome sequencing and phenotypic characterisation were performed, and patients were followed up for a median of 44 months. We analyzed the association of the variants with the clinical outcomes in a prospective study of 1,041 patients with sporadic DCM. truncating variants (tTTN) were detected in 120 (11.5%) patients as compared with 2.4/10,000 East Asian populations in the Genome Aggregation Database (GnomAD; < 0.0001). Pathogenic missense variants were also enriched in DCM as compared with the GnomAD populations (27.6 vs. 5.9%, < 0.0001). DCM patients with tTTN had a lower left ventricular ejection fraction (28.89 ± 8.72 vs. 31.81 ± 9.97, = 0.002) and a lower frequency of the left bundle branch block (3.3 vs. 11.3%, = 0.011) than those without or with mutations in other known causal genes (OCG). However, tTTN were not associated with the composite primary endpoint of cardiac death and heart transplantation during the follow-up period [adjusted hazard ratio (HR): 0.912; 95% confidence interval: 0.464-1.793; = 0.790]. There was also no sex-dependent effect. Concomitant tTTN and pathogenic variants in OCG were present in only eight DCM patients and did not affect the outcome. The phenotype of DCM caused by tTTN, major causes of sporadic DCM, is not distinctly different from those caused by other causal genes for DCM.
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http://dx.doi.org/10.3389/fcvm.2021.657689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120103PMC
April 2021

Prediction of HF-Related Mortality Risk Using Genetic Risk Score Alone and in Combination With Traditional Risk Factors.

Front Cardiovasc Med 2021 26;8:634966. Epub 2021 Apr 26.

Division of Cardiology, Department of Internal Medicine, Tongji Medical College, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China.

Common variants may contribute to the variation of prognosis of heart failure (HF) among individual patients, but no systematical analysis was conducted using transcriptomic and whole exome sequencing (WES) data. We aimed to construct a genetic risk score (GRS) and estimate its potential as a predictive tool for HF-related mortality risk alone and in combination with traditional risk factors (TRFs). We reanalyzed the transcriptomic data of 177 failing hearts and 136 healthy donors. Differentially expressed genes (fold change >1.5 or <0.68 and adjusted < 0.05) were selected for prognosis analysis using our whole exome sequencing and follow-up data with 998 HF patients. Statistically significant variants in these genes were prepared for GRS construction. Traditional risk variables were in combination with GRS for the construct of the composite risk score. Kaplan-Meier curves and receiver operating characteristic (ROC) analysis were used to assess the effect of GRS and the composite risk score on the prognosis of HF and discriminant power, respectively. We found 157 upregulated and 173 downregulated genes. In these genes, 31 variants that were associated with the prognosis of HF were finally identified to develop GRS. Compared with individuals with low risk score, patients with medium- and high-risk score showed 2.78 (95%CI = 1.82-4.24, = 2 × 10) and 6.54 (95%CI = 4.42-9.71, = 6 × 10) -fold mortality risk, respectively. The composite risk score combining GRS and TRF predicted mortality risk with an HR = 5.41 (95% CI = 2.72-10.64, = 1 × 10) for medium vs. low risk and HR = 22.72 (95% CI = 11.9-43.48, = 5 × 10) for high vs. low risk. The discriminant power of GRS is excellent with a C statistic of 0.739, which is comparable to that of TRF (C statistic = 0.791). The combination of GRS and TRF could significantly increase the predictive ability (C statistic = 0.853). The 31-SNP GRS could well distinguish those HF patients with poor prognosis from those with better prognosis and provide clinician with reference for the intensive therapy, especially when combined with TRF. https://www.clinicaltrials.gov/, identifier: NCT03461107.
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http://dx.doi.org/10.3389/fcvm.2021.634966DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107241PMC
April 2021

Divergence of Intracellular Trafficking of Sphingosine Kinase 1 and Sphingosine-1-Phosphate Receptor 3 in MCF-7 Breast Cancer Cells and MCF-7-Derived Stem Cell-Enriched Mammospheres.

Int J Mol Sci 2021 Apr 21;22(9). Epub 2021 Apr 21.

Lake Erie College of Osteopathic Medicine, Bradenton, FL 34211, USA.

Breast cancer MCF-7 cell-line-derived mammospheres were shown to be enriched in cells with a CD44+/CD24- surface profile, consistent with breast cancer stem cells (BCSC). These BCSC were previously reported to express key sphingolipid signaling effectors, including pro-oncogenic sphingosine kinase 1 (SphK1) and sphingosine-1-phosphate receptor 3 (S1P3). In this study, we explored intracellular trafficking and localization of SphK1 and S1P3 in parental MCF-7 cells, and MCF-7 derived BCSC-enriched mammospheres treated with growth- or apoptosis-stimulating agents. Intracellular trafficking and localization were assessed using confocal microscopy and cell fractionation, while CD44+/CD24- marker status was confirmed by flow cytometry. Mammospheres expressed significantly higher levels of S1P3 compared to parental MCF-7 cells ( < 0.01). Growth-promoting agents (S1P and estrogen) induced SphK1 and S1P3 translocation from cytoplasm to nuclei, which may facilitate the involvement of SphK1 and S1P3 in gene regulation. In contrast, pro-apoptotic cytokine tumor necrosis factor α (TNFα)-treated MCF-7 cells demonstrated increased apoptosis and no nuclear localization of SphK1 and S1P3, suggesting that TNFα can inhibit nuclear translocation of SphK1 and S1P3. TNFα inhibited mammosphere formation and induced S1P3 internalization and degradation. No nuclear translocation of S1P3 was detected in TNFα-stimulated mammospheres. Notably, SphK1 and S1P3 expression and localization were highly heterogenous in mammospheres, suggesting the potential for a large variety of responses. The findings provide further insights into the understanding of sphingolipid signaling and intracellular trafficking in BCs. Our data indicates that the inhibition of SphK1 and S1P3 nuclear translocation represents a novel method to prevent BCSCs proliferation.
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http://dx.doi.org/10.3390/ijms22094314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8122545PMC
April 2021

Circular RNAs of UDP-Glycosyltransferase () Genes Expand the Complexity and Diversity of the UGT Transcriptome.

Mol Pharmacol 2021 06 6;99(6):488-503. Epub 2021 Apr 6.

Department of Clinical Pharmacology and Flinders Cancer Centre, Flinders University, College of Medicine and Public Health, Flinders Medical Centre, Bedford Park, South Australia, Australia.

The human UDP-glycosyltransferase () gene superfamily generates 22 canonical transcripts coding for functional enzymes and also produces nearly 150 variant UGT transcripts through alternative splicing and intergenic splicing. In the present study, our analysis of circRNA databases identified backsplicing events that predicted 85 circRNAs from genes, with 33, 11, and 19 circRNAs from , , , respectively. Most of these UGT circRNAs were reported by one database and had low abundance in cell- or tissue-specific contexts. Using reverse-transcriptase polymerase chain reaction with divergent primers and cDNA samples from human tissues and cell lines, we found 13 circRNAs from four genes: (three), (one), (one), and (eight). Notably, all eight UGT8 circRNAs contain open reading frames that include the canonical start AUG codon and encode variant proteins that all have the common 274-amino acidN-terminal region of wild-type UGT8 protein. We further showed that one UGT8 circRNA (circ_UGT8-1) was broadly expressed in human tissues and cell lines, resistant to RNase R digestion, and predominately present in the cytoplasm. We cloned five UGT8 circRNAs into the Zinc finger with KRAB and SCAN domains 1 vector and transfected them into HEK293T cells. All these vectors produced both circRNAsand linear transcripts with varying circular/linear ratios (0.17-1.14).Western blotting and mass spectrometry assays revealed that only linear transcripts and not circRNAs were translated. In conclusion, our findings of nearly 100 circRNAs greatly expand the complexity and diversity of the UGT transcriptome; however, UGT circRNAs are expressed at a very low level in specific cellular contexts, and their biologic functions remain to be determined. SIGNIFICANCE STATEMENT: The human UGT gene transcriptome comprises 22 canonical transcripts coding for functional enzymes and approximately 150 alternatively spliced and chimeric variant transcripts. The present study identified nearly 100 circRNAs from genes, thus greatly expanding the complexity and diversity of the UGT transcriptome. UGT circRNAs were expressed broadly in human tissues and cell lines; however, most showed very low abundance in tissue- and cell-specific contexts, and therefore their biological functions remain to be investigated.
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http://dx.doi.org/10.1124/molpharm.120.000225DOI Listing
June 2021

Influence of temperature-dependent acoustic and thermal parameters and nonlinear harmonics on the prediction of thermal lesion under HIFU ablation.

Math Biosci Eng 2021 01;18(2):1340-1351

School of Information Science and Engineering, Changsha Normal University, Changsha 410100, China.

According to the traditional method of high intensity focused ultrasound (HIFU) treatment, the acoustic and thermal characteristic parameters of constant temperature (room temperature or body temperature) are used to predict thermal lesion. Based on the nonlinear spherical beam equation (SBE) and Pennes bio-heat transfer equation, and a new acoustic-thermal coupled model is proposed. The constant and temperature-dependent acoustic and thermal characteristic parameters are used to predict thermal lesion, and the predicted lesion area are compared with each other. Moreover, the relationship between harmonic amplitude ratio (P/P) and thermal lesion is studied. Combined with the known experimental data of acoustic and thermal characteristic parameters of biological tissue and data fitting method, the relationship between acoustic and thermal characteristic parameters and temperature is obtained; and the thermal lesion simulation calculation is carried out by using the acoustic and thermal characteristic parameters under constant temperature and temperature- dependent acoustic and thermal characteristic parameters, respectively. The simulation results show that under the same irradiation condition, the thermal lesion predicted by temperature-dependent acoustic and thermal characteristic parameters is larger than that predicted by traditional method, and the thermal lesion increases with the decrease of harmonic amplitude ratio.
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http://dx.doi.org/10.3934/mbe.2021070DOI Listing
January 2021

Paenibacillus glycinis sp. nov., an Endophytic Bacterium Isolated from the Nodules of Soybean (Glycine max (L.) Merr).

Curr Microbiol 2021 Apr 5;78(4):1678-1685. Epub 2021 Mar 5.

Departamento de Microbiología, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional, 11340, Cd. México, México.

A Gram-negative-staining, endospore-forming, rod-shaped bacterium, designated T1, was isolated from root nodules of soybean (Glycine max (L.) Merr) in Heilongjiang Province of China. The isolate was identified as a member of the genus Paenibacillus based on phenotypic and phylogenetic characteristics. The 16S rRNA sequence was closely related to that of Paenibacillus sacheonensis SY01 with a similarity of 98.4%. Average nucleotide identity and in silico DNA-DNA hybridization values between strain T1 and P. sacheonensis DSM 23054 were 81.4% and 25.4%, respectively. The DNA G + C content of strain T1 was 58.2 mol%. meso-Diaminopimelic acid was detected in the cell-wall peptidoglycan. The major cellular fatty acids were anteiso-C, iso-C and iso-C. The predominant respiratory quinone was MK-7. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, five unidentified phospholipids, four unidentified aminophospholipids, an unidentified glycolipid and an unidentified lipid. Based on these results, T1 is considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus glycinis sp. nov. is proposed. The type strain is T1 (= CGMCC 1.18563 = KCTC43227).
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http://dx.doi.org/10.1007/s00284-021-02403-1DOI Listing
April 2021

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition).

Autophagy 2021 Jan 8;17(1):1-382. Epub 2021 Feb 8.

University of Crete, School of Medicine, Laboratory of Clinical Microbiology and Microbial Pathogenesis, Voutes, Heraklion, Crete, Greece; Foundation for Research and Technology, Institute of Molecular Biology and Biotechnology (IMBB), Heraklion, Crete, Greece.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field.
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http://dx.doi.org/10.1080/15548627.2020.1797280DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7996087PMC
January 2021

Structural and molecular basis for foot-and-mouth disease virus neutralization by two potent protective antibodies.

Protein Cell 2021 Feb 18. Epub 2021 Feb 18.

State Key Laboratory of Veterinary Etiological Biology and National Foot and Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China.

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http://dx.doi.org/10.1007/s13238-021-00828-9DOI Listing
February 2021

Bi-functional gold nanocages enhance specific immunological responses of foot-and-mouth disease virus-like particles vaccine as a carrier and adjuvant.

Nanomedicine 2021 04 20;33:102358. Epub 2021 Jan 20.

State Key Laboratory of Veterinary Etiological Biology and Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China; School of Animal Science, Yangtze University, Jingzhou, PR China.. Electronic address:

Virus-like particle (VLP) vaccines have become one of the dominant vaccine candidates for foot-and-mouth disease (FMD). To further enhance the immunogenicity of VLP vaccines, gold nanocages (AuNCs) were selected as an adjuvant for the vaccine. Our experiments demonstrated that AuNCs had little biotoxicity in vivo and in vitro and improved the uptake of VLP in BHK-21 and RAW264.7 cell lines. The VLP-AuNCs activated DCs mainly through toll-like receptor 4 (TLR4) and promoted the secretion of IL-6, IL-1β, and TNF-α. The conjugation of VLP and AuNCs triggered a strong immune response against FMD virus (FMDV) in mice and guinea pigs. The VLP-AuNCs significantly enhanced the proliferation of CD8 T cells (P < 0.05) and the secretion of cellular immune-related cytokines (IFN-γ, P < 0.05; IL-12p70, P < 0.01) compared with VLP. The present study demonstrated that AuNCs, as a great potential adjuvant for FMDV VLP vaccines, significantly enhance the immune response.
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http://dx.doi.org/10.1016/j.nano.2021.102358DOI Listing
April 2021

Development and validation of a competitive ELISA based on virus-like particles of serotype Senecavirus A to detect serum antibodies.

AMB Express 2021 Jan 6;11(1). Epub 2021 Jan 6.

State Key Laboratory of Veterinary Etiological Biology and Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Xujiaping 1, Lanzhou, 730046, Gansu, People's Republic of China.

Virus-like particles (VLPs) are high-priority antigens with highly ordered repetitive structures, which are similar to natural viral particles. We have developed a competitive enzyme-linked immunosorbent assay (cELISA) for detecting antibodies directed against Senecavirus A (SVA). Our assay utilizes SVA VLPs that were expressed and assembled in an E. coli expression system as the coating antigens. VLPs have better safety and immunogenicity than intact viral particles or peptides. The VLPs-based cELISA was used to test 342 serum samples collected from different pig farms, and the results showed that its specificity and sensitivity were 100% and 94%, respectively. The consistency rates of cELISA with the BIOSTONE AsurDx™ Senecavirus A (SVA) Antibody Test Kit and an indirect immunofluorescent assay were 90.0% and 94.2%, respectively. Therefore, this VLPs-based cELISA can be effectively and reliably used for the detection and discrimination of SVA infection in serum samples.
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http://dx.doi.org/10.1186/s13568-020-01167-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7787412PMC
January 2021

Streptomyces sp. strain TOR3209: a rhizosphere bacterium promoting growth of tomato by affecting the rhizosphere microbial community.

Sci Rep 2020 11 18;10(1):20132. Epub 2020 Nov 18.

Key Laboratory of Plants Genetic Engineering Center, Institute of Genetics and Physiology (Hebei Agricultural Products Quality and Safety Research Center), Hebei Academy of Agriculture and Forestry Sciences, Shijiazhuang, Hebei, 050000, People's Republic of China.

Aiming at revealing the possible mechanism of its growth promoting effect on tomato, the correlations among Streptomyces sp. TOR3209 inoculation, rhizobacteriome, and tomato growth/production traits were investigated in this study. By analyses of Illumina sequencing and plate coating, differences in rhizosphere microbial communities were found in different growth stages and distinct inoculation treatments. The plant biomass/fruit yields and relative abundances of families Flavobacteriaceae, Sphingobacteriaceae, Polyangiaceae and Enterobacteriaceae in treatments T (tomato inoculated with TOR3209) and TF (tomato inoculated with TOR3209 + organic fertilizer) were higher than that in the controls (CK and CK+ organic fertilizer), respectively. The analysis of Metastats and LEfSe revealed that the genera Flavobacterium and Sorangium in seedling stage, Klebsiella in flowering stage, Collimonas in early fruit setting stage, and genera Micrococcaceae, Pontibacte and Adhaeribacter in late fruit setting stage were the most representative rhizobacteria that positively responded to TOR3209 inoculation. By cultivation method, five bacterial strains positively correlated to TOR3209 inoculation were isolated from rhizosphere and root endosphere, which were identified as tomato growth promoters affiliated to Enterobacter sp., Arthrobacter sp., Bacillus subtilis, Rhizobium sp. and Bacillus velezensis. In pot experiment, TOR3209 and B. velezensis WSW007 showed joint promotion to tomato production, while the abundance of inoculated TOR3209 was dramatically decreased in rhizosphere along the growth of tomato. Conclusively, TOR3209 might promote the tomato production via changing of microbial community in rhizosphere. These findings provide a better understanding of the interactions among PGPR in plant promotion.
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http://dx.doi.org/10.1038/s41598-020-76887-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7675979PMC
November 2020

The Expression Profiles of ADME Genes in Human Cancers and Their Associations with Clinical Outcomes.

Cancers (Basel) 2020 Nov 13;12(11). Epub 2020 Nov 13.

Department of Clinical Pharmacology and Flinders Cancer Centre, Flinders University, College of Medicine and Public Health, Flinders Medical Centre, Bedford Park, Adelaide 5042, SA, Australia.

ADME genes are a group of genes that are involved in drug absorption, distribution, metabolism, and excretion (ADME). The expression profiles of ADME genes within tumours is proposed to impact on cancer patient survival; however, this has not been systematically examined. In this study, our comprehensive analyses of pan-cancer datasets from the Cancer Genome Atlas (TCGA) revealed differential intratumoral expression profiles for ADME genes in 21 different cancer types. Most genes also showed high interindividual variability within cancer-specific patient cohorts. Using Kaplan-Meier plots and logrank tests, we showed that intratumoral expression levels of twenty of the thirty-two core ADME genes were associated with overall survival (OS) in these cancers. Of these genes, five showed significant association with unfavourable OS in three cancers, including SKCM (, ), KIRC (, ), PAAD (); sixteen showed significant associations with favourable OS in twelve cancers, including BLCA (), BRCA (), COAD (), HNSC (), KIRC (, , , ), KIRP (), LIHC (, , , , ), LUAD (), LUSC (), PAAD (), SARC (), and SKCM (). Overall, these data provide compelling evidence supporting ADME genes as prognostic biomarkers and potential therapeutic targets. We propose that intratumoral expression of ADME genes may impact cancer patient survival by multiple mechanisms that can include metabolizing/transporting anticancer drugs, activating anticancer drugs, and metabolizing/transporting a variety of endogenous molecules involved in metabolically fuelling cancer cells and/or controlling pro-growth signalling pathways.
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http://dx.doi.org/10.3390/cancers12113369DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7697355PMC
November 2020

Identification of Key Genes in Lung Adenocarcinoma and Establishment of Prognostic Mode.

Front Mol Biosci 2020 27;7:561456. Epub 2020 Oct 27.

School of Medicine, Anhui University of Science and Technology, Huainan, China.

Background: The development of human tumors is associated with the abnormal expression of various functional genes, and a massive tumor-based database needs to be deeply mined. Based on a multigene prediction model, access to urgent prognosis of patients has become possible.

Materials And Methods: We selected three RNA expression profiles (GSE32863, GSE10072, and GSE43458) from the lung adenocarcinoma (LUAD) database of the Gene Expression Omnibus (GEO) and analyzed the differentially expressed genes (DEGs) between tumor and normal tissue using GEO2R program. After that, we analyzed the transcriptome data of 479 LUAD samples (54 normal tissue samples and 425 cancer tissue samples) and their clinical follow-up data from the (TCGA) database. Kaplan-Meier (KM) curve and receiver operating characteristic (ROC) were used to assess the prediction model. Multivariate Cox analysis was used to identify independent predictors. TCGA pancreatic adenocarcinoma datasets were used to establish a nomogram model.

Results: We found 98 significantly prognosis-related genes using KM and COX analysis, among which six genes were found to be the DEGs in GEO. Using multivariate analysis, it was found that a single gene could not be used as an independent predictor of prognosis. However, the risk score calculated by weighting these six genes could serve as an independent prognosis predictor. COX analysis performed with multiple covariates such as age, gender, tumor stage, and TNM typing showed that risk score could still be utilized as an independent risk factor for patient survival rate ( = 0.013) and had an applicable reliability (area under the curve, AUC = 0.665). By combining risk score and various clinical features, the nomogram model was constructed, which had been proven to have high consistency for the prediction of 3- and 5-year survival rate (concordance = 0.751) and high accuracy as tested by ROC (AUC = 0.71;AUC = 0.708).

Conclusion: We proposed a method to predict the prognosis of LUAD by weighting multiple genes and constructed a nomogram model suitable for the prognostic evaluation of LUAD, which could provide a new tool for the identification of therapeutic targets and the efficacy evaluation of LUAD.
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http://dx.doi.org/10.3389/fmolb.2020.561456DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653064PMC
October 2020

Association of air temperature with pediatric intussusception in northeastern China: A 10-year retrospective study.

Am J Emerg Med 2021 04 10;42:211-216. Epub 2020 Nov 10.

Department of Pediatric Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. Electronic address:

Objective: The aim of this study was to determine whether an association existed between intussusception and air temperature.

Methods: A retrospective study was performed between March 2006 and February 2016 to determine the relationship between pediatric primary intussusception (PPI) and air temperature. Information from hospital records of 5922 cases of PPI and Mean daily temperatures of Shenyang were obtained. Pearson correlation analysis was used to examine the association between monthly PPI cases and monthly mean temperature. Factorial analysis-of-variance was used to examine differences in the numbers of seasonal PPI cases during different seasons.

Results: Monthly PPI cases fluctuated throughout the year, with a peak in June, and a trough in February. Pearson correlation analysis showed that monthly PPI cases was associated with the monthly mean temperature (p < 0.01). Factorial analysis-of-variance showed there was significant difference in the numbers of seasonal PPI cases during different seasons. Multiple comparison showed a significant difference in seasonal PPI cases between spring and summer, spring and winter, summer and autumn, summer and winter, autumn and winter (p < 0.01).

Conclusions: Monthly PPI cases were positively associated with monthly mean temperature in Shenyang. The incidence of intussusception shows a seasonal trend, with a peak in summer (May to July).
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http://dx.doi.org/10.1016/j.ajem.2020.11.012DOI Listing
April 2021

Graphene-based low-threshold and tunable optical bistability in one-dimensional photonic crystal Fano resonance heterostructure at optical communication band.

Opt Express 2020 Nov;28(23):34948-34959

In this paper, the one-dimensional photonic crystal Fano resonance heterostructure is used to achieve low-threshold and tunable graphene-based optical bistability of the transmitted and reflected light beam at optical communication band. The low-threshold of optical bistability (OB) originates from the local field enhancement owing to the Fano resonance excited by topological edge states mode and Fabry-Perot cavity mode. The study found that it is feasible to continuously adjust the hysteresis behavior and optical bistable thresholds by altering the Fermi energy of the left and right graphene respectively. Furthermore, the OB can also be controlled by changing the number of graphene layers or the angle of incident beam, which makes this structure a feasible object of experimental research at optical communication band in the future.
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http://dx.doi.org/10.1364/OE.408632DOI Listing
November 2020

[Promotion of self-nucleic acid fragments on the assembly of foot-and-mouth disease virus-like particles].

Sheng Wu Gong Cheng Xue Bao 2020 Oct;36(10):2076-2082

National Foot and Mouth Disease Reference Laboratory, State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, Gansu, China.

The special nucleic acid fragments, 5' untranslated region (5' UTR) and internal ribosome entry site (IRES) of foot-and-mouth disease virus (FMDV), which interact with the capsid proteins, were selected as scaffolds to investigate the assembly efficiency of foot-and-mouth disease (FMD) virus-like particles (VLPs). The assembled product was characterized by evaluation of particle size, surface potential, gel retardation assay, nuclease digestion experiments, size-exclusion chromatography, transmission electron microscopy and circular dichroism analysis. The results confirmed that the 5' UTR and IRES of FMDV co-assembled with the FMD VLPs and facilitated the assembly efficiency of FMD-VLPs. It demonstrates that the assembly efficiency of 75S particles of VLPs-5'UTR was significantly higher than those of the VLPs (P<0.001) and VLPs-IRES group (P<0.01). Comparatively the assembly efficiency of 12S particles of VLPs-IRES was significantly higher than those of the VLPs (P<0.000 1) and VLPs-5'UTR (P<0.000 1). It showed that the 5' UTR represented more effective in facilitating the assembly of VLPs. This study proposes an optimized strategy for improving the assembly efficiency of VLPs for the development of VLPs vaccine.
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http://dx.doi.org/10.13345/j.cjb.200084DOI Listing
October 2020

Exosomes released by human umbilical cord mesenchymal stem cells protect against renal interstitial fibrosis through ROS-mediated P38MAPK/ERK signaling pathway.

Am J Transl Res 2020 15;12(9):4998-5014. Epub 2020 Sep 15.

Department of Urology, Children's Hospital of Chongqing Medical University Chongqing 400014, China.

Mesenchymal stem cells (MSCs) and their conditioned medium attenuate renal fibrosis in an irreversible model of unilateral ureteral obstruction (UUO). However, the key components that play a role in the paracrine effects of MSCs and their mechanisms of action are not well understood. Therefore, in this study, we investigated whether exosomes released by human umbilical cord mesenchymal stem cells (hucMSC-Ex) would be able to attenuate renal fibrosis in an irreversible model of UUO and further explored potential mechanisms. In vivo, rats were divided into four groups: sham operation, sham operation transplanted with hucMSC-Ex, UUO, and UUO transplanted with hucMSC-Ex. hucMSC-Ex was administered via the left renal artery after total ligation of the left ureter. Rats were sacrificed after 14 days of obstruction. Renal function such as serum creatinine (Scr) or blood urea nitrogen (BUN) were monitored over the period. Histological changes, proliferation and apoptosis in tubular epithelial cells, and the levels of oxidative stress were measured. In vitro, NRK-52E cells were incubated with or without 5 ng/ml TGF-β1 and co-incubated with or without hucMSC-Ex for 48 h. Apoptosis and the levels of oxidative stress of NRK-52E cells were also measured. In the UUO group, the level of BUN and Scr, and the level of apoptosis and oxidative stress were all increased. In addition, the renal tubular injury and tubulointerstitial fibrosis were evident. However, all the above indices decreased significantly after treatment with hucMSC-Ex. , hucMSC-Ex significantly inhibited TGF-β1-induced apoptosis of NRK-52E cells by altering the production of ROS. Furthermore, it was observed that hucMSC-Ex inhibited apoptosis by inhibiting the activation of p38 mitogen-activated protein kinase (p38MAPK)/extracellular-signal-regulated kinase (ERK) 1/2 pathway. In conclusion, the results showed that hucMSC-Ex had positive effects towards UUO-induced renal fibrosis and apoptosis of renal tubular epithelial cells, and its mechanism of action was associated with inhibition of ROS-mediated p38MAPK/ERK signaling pathway. These data suggest the potential application of hucMSC-Ex in the treatment of chronic kidney disease, and also reveal the underlying mechanism of hucMSC-Ex action.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7540090PMC
September 2020
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