Publications by authors named "Qianqian Chen"

149 Publications

Grb2 Induces Cardiorenal Syndrome Type 3: Roles of IL-6, Cardiomyocyte Bioenergetics, and Akt/mTOR Pathway.

Front Cell Dev Biol 2021 22;9:630412. Epub 2021 Mar 22.

Department of Nephrology, Chinese PLA General Hospital, Chinese PLA Institute of Nephrology, State Key Laboratory of Kidney Diseases, National Clinical Research Center for Kidney Diseases, Beijing Key Laboratory of Kidney Diseases, Beijing, China.

Cardiorenal syndrome type 3 (CRS-3) is damage to the heart following acute kidney injury (AKI). Although many experiments have found that inflammation, oxidative stress, and cardiomyocyte death are involved in cardiomyocyte pathophysiological alterations during CRS-3, they lack a non-bias analysis to figure out the primary mediator of cardiac dysfunction. Herein proteomic analysis was operated in CRS-3 and growth factor receptor-bound protein 2 (Grb2) was identified as a regulator involving AKI-related myocardial damage. Increased Grb2 was associated with cardiac diastolic dysfunction and mitochondrial bioenergetics impairment; these pathological changes could be reversed through the administration of a Grb2-specific inhibitor during AKI. Molecular investigation illustrated that augmented Grb2 promoted cardiomyocyte mitochondrial metabolism disorder through inhibiting the Akt/mTOR signaling pathway. Besides that, Mouse Inflammation Array Q1 further identified IL-6 as the upstream stimulator of Grb2 upregulation after AKI. Exogenous administration of IL-6 induced cardiomyocyte damage and mitochondrial bioenergetics impairment, whereas these effects were nullified in cardiomyocytes pretreated with Grb2 inhibitor. Our results altogether identify CRS-3 to be caused by the upregulations of IL-6/Grb2 which contribute to cardiac dysfunction through inhibiting the Akt/mTOR signaling pathway and inducing cardiomyocyte mitochondrial bioenergetics impairment. This finding provides a potential target for the clinical treatment of patients with CRS-3.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fcell.2021.630412DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019825PMC
March 2021

Investigation on the Incidence of Syncope in Children and Adolescents Aged 2-18 Years in Changsha.

Front Pediatr 2021 22;9:638394. Epub 2021 Mar 22.

Department of Pediatric Cardiovasology, Children's Medical Center, The Second Xiangya Hospital, Central South University, Changsha, China.

Syncope is a common clinical symptom, while there are less relevant literature and targeted research on childhood morbidity. This article makes a cross-section survey on the incidence of syncope in children and adolescents aged 2-18 years in Changsha. There were 4,352 children and adolescents aged 2-18 years randomly selected from six primary and secondary schools and three kindergartens in Changsha from March 2018 to November 2018. There were 4,916 standardized questionnaires issued, and 4,352 (88.53%) valid questionnaires were recovered. (1) Incidence: 17.37% of children and adolescents aged 2-18 years who had at least more than one syncope; the incidence in the adolescence (28.85%) was higher than that in the school age (8.32%) and in the preschool age (2.71%) ( < 0.01). (2) Age at onset: 13.9 ± 3.1 years old, with a peak age of 16 years. (3) Gender difference: The incidence in adolescent females was higher than that in males (31.72 vs. 26.25%, < 0.05). In inducements, females had higher rates than males in sweltering environment ( < 0.01), whereas males had higher rates than females in urination ( < 0.05). Dizziness, nausea, sweating, and facial pallor were higher in females than in males in presyncope ( < 0.05). The incidence of syncope in children and adolescents aged 2-18 years in Changsha is 17.37%. The incidence of syncope is different between males and females in different age groups; there are gender differences in syncope inducements and presyncope.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fped.2021.638394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8019745PMC
March 2021

Quantitative analysis of contrast enhanced spectral mammography grey value for early prediction of pathological response of breast cancer to neoadjuvant chemotherapy.

Sci Rep 2021 Mar 15;11(1):5892. Epub 2021 Mar 15.

Department of Radiology, Yantai Yuhuangding Hospital, Affiliated Hospital of Qingdao University, No. 20 Yuhuangding East Road, Yantai, 264000, Shandong, People's Republic of China.

A quantitative analysis of contrast-enhanced spectral mammography (CESM) enhancement was conducted for the early prediction of the pathological response after neoadjuvant chemotherapy (NAC). Retrospective analysis of the data of 111 patients was conducted, and all of them underwent NAC in our hospital and surgical resection after the end of all cycles from January 2018 to May 2019. They were divided into pathological complete response (PCR) and non-PCR groups. We determined whether a statistical difference in the percentage of CESM grey value reduction (ΔCGV) was present in the PCR and non-PCR groups and whether a statistical difference was observed in the diagnostic efficiency of craniocaudal (CC) and mediolateral oblique (MLO) view subtraction images. Independent sample t-test was used to compare different groups, the receiver operating characteristic (ROC) curve was used to compare the diagnostic efficacy of CC and MLO for pathological response after NAC, and the Delong test was used to compare the area under the ROC curve (AUC). Statistical significance was considered at P < 0.05. A statistical difference was observed in the ΔCGV in the PCR and non-PCR groups. No statistical difference was observed in the AUCs of CC and MLO view subtraction images. The ΔCGV can be used as a quantitative index to predict PCR early, and no statistical difference was observed in the diagnostic efficacy of CC and MLO view subtraction images.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-021-85353-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7960703PMC
March 2021

Prolactin Is Associated With Insulin Resistance and Beta-Cell Dysfunction in Infertile Women With Polycystic Ovary Syndrome.

Front Endocrinol (Lausanne) 2021 25;12:571229. Epub 2021 Feb 25.

Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.

Background: Our study aimed to investigate if serum prolactin (PRL) levels associated with insulin resistance and beta-cell dysfunction in infertile patients with polycystic ovary syndrome (PCOS).

Methods: This was a retrospective cross-sectional study performed in the reproductive medicine center of the first affiliated hospital of Wenzhou Medical University. From January 2007 to August 2018, a total of 792 PCOS and 700 non-PCOS infertile women were included. All patients' prolactin levels were in the normal range. PCOS was diagnosed according to the Rotterdam Criteria. Anthropometric parameters, blood pressure, serum prolactin levels, sex hormones, fasting lipids, fasting plasma glucose (FPG), fasting insulin (FINS) and hepatic biological parameters were measured in all subjects.

Results: Serum prolactin levels in PCOS women were significantly decreased compared with levels in non-PCOS women after adjusting for age and BMI ( < 0.05). Moreover, we found that prolactin levels were positively associated with high-density lipoprotein cholesterol (HDL-C) and negatively associated with age, BMI, waist circumference (WC), hip circumference (HC), luteinizing hormone/follicle stimulating hormone (LH/FSH), estradiol (E), FINS, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β (HOMA-β), triglyceride (TG) and alanine aminotransferase (ALT) ( < 0.05). After adjusting for age and BMI, multiple linear regression analysis revealed that LH, LH/FSH, E, FINS, HOMA-IR, and HOMA-β were negatively associated with serum PRL ( < 0.05).

Conclusions: Low serum PRL levels within the normal range associates with a higher incidence of insulin resistance and beta-cell dysfunction in infertile women with PCOS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fendo.2021.571229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7947819PMC
February 2021

Curcumin induces ferroptosis in non-small-cell lung cancer via activating autophagy.

Thorac Cancer 2021 Mar 3. Epub 2021 Mar 3.

Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, China.

Background: Emerging studies showed curcumin can inhibit glioblastoma and breast cancer cells via regulating ferroptosis. However, the role of ferroptosis in the inhibitory effect of curcumin on non-small-cell lung cancer (NSCLC) remains unclear.

Methods: Cell counting kit-8 (CCK-8) assay was used to measure the viability of A549 and H1299 cells under different conditions. Cell proliferation was examined by Ki67 immunofluorescence. The morphological changes of cells and tumor tissues were observed by optical microscope and hematoxylin and eosin (H&E) staining. Intracellular reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), and iron contents were determined by corresponding assay kit. The related protein expression levels were detected by western blot and immunohistochemistry. Transmission electron microscope was used to observe ultrastructure changes of A549 and H1299 cells.

Results: Curcumin inhibited tumor growth and cell proliferation, but promoted cell death. Characteristic changes of ferroptosis were observed in curcumin group, including iron overload, GSH depletion and lipid peroxidation. Meanwhile, the protein level of ACSL4 was higher and the levels of SLC7A11 and GPX4 were lower in curcumin group than that in control group. Incubation of ferroptosis inhibitors ferrostatin-1 (Fer-1) or knockdown of iron-responsive element-binding protein 2 (IREB2) notably weakened curcumin-induced anti-tumor effect and ferroptosis in A549 and H1299 cells. Further investigation suggested that curcumin induced mitochondrial membrane rupture and mitochondrial cristae decrease, increased autolysosome, increased the level of Beclin1 and LC3, and decreased the level of P62. Curcumin-induced autophagy and subsequent ferroptosis were both alleviated with autophagy inhibitor chloroquine (CQ) or siBeclin1.

Conclusion: Curcumin induced ferroptosis via activating autophagy in NSCLC, which enhanced the therapeutic effect of NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/1759-7714.13904DOI Listing
March 2021

Gut flora-targeted photobiomodulation therapy improves senile dementia in an Aß-induced Alzheimer's disease animal model.

J Photochem Photobiol B 2021 Mar 10;216:112152. Epub 2021 Feb 10.

Laser Medicine Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Science & Peking Union Medical College, Tianjin 300192, China.

Background: Emerging evidence suggests that the gut microbiota plays an important role in the pathological progression of Alzheimer's disease (AD). Photobiomodulation (PBM) therapy is believed to have a positive regulatory effect on the imbalance of certain body functions, including inflammation, immunity, wound healing, nerve repair, and pain. Previous studies have found that the intestinal flora of patients with AD is in an unbalanced state. Therefore, we have proposed the use of gut flora-targeted PBM (gf-targeted PBM) as a method to improve AD in an Aß-induced AD mouse model.

Methods: PBM was performed on the abdomen of the mice at the wavelengths of 630 nm, 730 nm, and 850 nm at 100 J/cm for 8 weeks. Morris water maze test, immunofluorescence and proteomic of hippocampus, and intestinal flora detection of fecal were used to evaluate the treatment effects of gf-targeted PBM on AD rats.

Results: PBM at all three wavelengths (especially 630 nm and 730 nm) significantly improved learning retention as measured by the Morris water maze. In addition, we found reduced amyloidosis and tau phosphorylation in the hippocampus by immunofluorescence in AD mice. By using a quantitative proteomic analysis of the hippocampus, we found that gf-targeted PBM significantly altered the expression levels of 509 proteins (the same differentially expressed proteins in all three wavelengths of PBM), which involved the pathways of hormone synthesis, phagocytosis, and metabolism. The 16 s rRNA gene sequencing of fecal contents showed that PBM significantly altered the diversity and abundance of intestinal flora. Specifically, PBM treatment reversed the typical increase of Helicobacter and uncultured Bacteroidales and the decrease of Rikenella seen in AD mice.

Conclusions: Our data indicate that gf-targeted PBM regulates the diversity of intestinal flora, which may improve damage caused by AD. Gf-targeted PBM has the potential to be a noninvasive microflora regulation method for AD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jphotobiol.2021.112152DOI Listing
March 2021

Intermittent hypoxia-induced autophagy via AMPK/mTOR signaling pathway attenuates endothelial apoptosis and dysfunction in vitro.

Sleep Breath 2021 Jan 22. Epub 2021 Jan 22.

Department of Respiratory and Critical Care, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin, 300052, China.

Purpose: The aim of this study was to examine whether or not intermittent hypoxia (IH) upregulated autophagy and the contributions of autophagy to endothelial apoptosis and dysfunction in human umbilical vein endothelial cells (HUVECs).

Method: HUVECs were incubated under normoxia and IH conditions. After 3-, 6-, 12-, and 24-h exposure, the autophagic vacuoles and autophagosomes were observed by transmission electron microscopy and monodansylcadaverine staining. The protein levels of autophagy-related biomarkers and AMPK/mTOR pathway were measured by Western blot. The apoptosis-related proteins and the percentage of apoptotic cells were evaluated by Western blot and flow cytometry, respectively, while the levels of endothelial function biomarkers were assessed by ELISA.

Results: IH induced autophagy, as determined by the increased numbers of the autophagic vacuoles, autophagosomes, and by the elevated levels of Beclin-1 protein, the LC3II/LC3I ratio, and p62 degradation. IH-induced autophagic flux peaked at 12-h duration and weakened at 24 h. IH increased the ratio of p-AMPK/AMPK and decreased the ratio of p-mTOR/mTOR, while compound C restored the alteration. A significant decrease in the Bcl-2 level and the Bcl-2/Bax ratio and a significant increase in the protein expression levels of Bax and cleaved caspase 3 and in the percentage of apoptosis were observed under IH exposure. Moreover, the NO level was reduced, while the ET-1 and VEGF levels were raised under IH condition. These alterations were suppressed by the pretreatment of 3-methyladenine.

Conclusions: IH upregulates autophagy through AMPK/mTOR pathway in HUVECs in vitro, which might be protective against endothelial apoptosis and dysfunction caused by IH.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11325-021-02297-0DOI Listing
January 2021

Background parenchymal enhancement on contrast-enhanced spectral mammography does not represent an influencing factor for breast cancer: A preliminary study.

Medicine (Baltimore) 2020 Dec;99(52):e23857

Department of Radiology, Yantai Yuhuangding Hospital, Affiliated Hospital of Qingdao University, Yantai, Shandong.

Abstract: To compare the relationship between background parenchymal enhancement (BPE) on contrast-enhanced spectral mammography (CESM), mammographic breast density (MBD), age, in the group with benign vs malignant breast lesions.Four hundred thirty three non-high-risk patients from January 2018 to May 2019 were retrospectively analyzed. Patients were assigned into 4 groups: premenopausal benign lesions, premenopausal malignant lesions, postmenopausal benign lesions, and postmenopausal malignant lesions. The differences in CESM BPE and MBD between premenopausal benign lesions and premenopausal malignant lesions, between postmenopausal benign lesions and postmenopausal malignant lesions, between premenopausal and postmenopausal benign lesions, and between premenopausal and postmenopausal malignant lesions were evaluated. Pearson Chi-Squared test was used to analyze the differences between the above groups. Spearman rank correlation analysis was used to evaluate the correlations between BPE, MBD, and age. Multiple logistic regression was used to analyze the influencing factors of breast cancer. P < .05 was considered statistically significant.There was no significant difference in CESM BPE or MBD of benign and malignant lesions regardless of premenopausal or postmenopausal status, but there was a significant difference in CESM BPE and MBD of premenopausal and postmenopausal patients regardless of the presence of benign or malignant lesions. The intensity of CESM BPE was positively correlated with MBD, and the intensity of CESM BPE and MBD were negatively correlated with age. Multiple logistic regression analysis showed that age was an influencing factor for breast cancer in both premenopausal and postmenopausal patients.For non-high-risk women, CESM BPE and MBD were not correlated with benign or malignant breast lesions, and age was an influencing factor for breast cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000023857DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769306PMC
December 2020

Influence of coexistence of mild OSA on airway mucus hypersecretion in patients with COPD.

J Breath Res 2020 Dec 18. Epub 2020 Dec 18.

Department of Respiratory and Critical Care Medicine, Tianjin Medical University General Hospital, Tianjin, 300052, CHINA.

Purpose: The coexistence of chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (OSA) can cause multiple system damage, and the main physiological mechanisms are continuous hypoxia and intermittent hypoxia (IH). Airway mucus hypersecretion is an important clinical feature of COPD, which can cause a progressive decline of lung function, acute COPD aggravation, and disease progression. The purpose of our study is to determine the influence of the coexistence of mild OSA on airway mucus hypersecretion.

Patients And Methods: Clinical data and airway epithelial samples were collected. The average fluorescence intensity of MUC5AC and the number of goblet cells were measured through immunofluorescence staining. MUC5AC expression was measured in human bronchial epithelial (HBE) cells exposed to normoxia, IH, particulate matter (PM), and PM+IH using real-time quantitative polymerase chain reaction and western blotting.

Results: FEV1% pred and FEV1/FVC were higher in patients with COPD-OSA overlap syndrome(OS) than in patients with COPD alone. Patients with OS had less sputum volume than patients with COPD alone.MUC5AC expression and the number of goblet cells in the airway epithelium in the COPD alone group were significantly higher than those in the OS groups. The PM+IH group had lower MUC5AC mRNA and protein expression in HBE cells than the PM group.

Conclusions: The coexistence of mild OSA may reduce goblet cell proliferation and MUC5AC expression in the airway epithelium of patients with COPD. Mild IH inhibited PM-induced up-regulation of MUC5AC expression in the mRNA and protein levels in HBE cells.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1088/1752-7163/abd52eDOI Listing
December 2020

Characterization of an IncR Plasmid with Two Copies of IS-Linked from ST.

Int J Genomics 2020 24;2020:3484328. Epub 2020 Nov 24.

Institute of Biomedical Informatics, Wenzhou Medical University, Wenzhou 325035, China.

To characterize the molecular structure of IncR plasmid-related sequences, comparative genomic analysis was conducted using 261 IncR plasmid backbone-related sequences. Among the sequences, 257 were IncR plasmids including the multidrug-resistance IncR plasmid pR50-74 from strain R50 of this work, and the other four were from bacterial chromosomes. The IncR plasmids were derived from different bacterial genera or species, mainly (70.82%, 182/257), (11.28%, 29/257), (7.00%, 18/257), and (3.50%, 9/257). The bacterial chromosomes carrying IncR plasmid backbone sequences were derived from AOUC-001 and KPN1344, among others. The IncR backbone sequence of AOUC-001 chromosome shows the highest identity with that of pR50-74. Complex class 1 integrons carrying various copies of IS (IS-linked unit) were identified in IncR plasmids. In addition to two consecutive copies of --, the other resistance genes encoded on pR50-74 are all related to mobile genetic elements, such as IS, IS, and the class 1 integron. This study provides a clear understanding of the mobility and plasticity of the IncR plasmid backbone sequence and emphasizes the important role of IS in the recruitment of multicopy resistance genes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2020/3484328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7707992PMC
November 2020

Cardiac fibroblast miR-27a may function as an endogenous anti-fibrotic by negatively regulating Early Growth Response Protein 3 (EGR3).

J Cell Mol Med 2021 Jan 20;25(1):73-83. Epub 2020 Nov 20.

Nursing Department, Hainan Maternal and Child Health Hospital, Haikou, China.

Pathological myocardial fibrosis and hypertrophy occur due to chronic cardiac stress. The microRNA-27a (miR-27a) regulates collagen production across diverse cell types and organs to inhibit fibrosis and could constitute an important therapeutic avenue. However, its impact on hypertrophy and cardiac remodelling is less well-known. We employed a transverse aortic constriction (TAC) murine model of left ventricular pressure overload to investigate the in vivo effects of genetic miR-27a knockout, antisense inhibition of miR-27a-5p and fibroblast-specific miR-27a knockdown or overexpression. In silico Venn analysis and reporter assays were used to identify miR-27a-5p's targeting of Early Growth Response Protein 3 (Egr3). We evaluated the effects of miR-27a-5p and Egr3 upon transforming growth factor-beta (Tgf-β) signalling and secretome of cardiac fibroblasts in vitro. miR-27a-5p attenuated TAC-induced cardiac fibrosis and myofibroblast activation in vivo, without a discernible effect on cardiac myocytes. Molecularly, miR-27a-5p inhibited transforming growth factor-beta (Tgf-β) signalling and pro-fibrotic protein secretion in cardiac fibroblasts in vitro through suppressing the pro-fibrotic transcription factor Early Growth Response Protein 3 (Egr3). This body of work suggests that cardiac fibroblast miR-27a may function as an endogenous anti-fibrotic by negatively regulating Egr3 expression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jcmm.15814DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7810947PMC
January 2021

The SUMOylation of TAB2 mediated by TRIM60 inhibits MAPK/NF-κB activation and the innate immune response.

Cell Mol Immunol 2020 Nov 12. Epub 2020 Nov 12.

Department of Rheumatology and Immunology, National Clinical Research Center for Geriatrics, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, and Collaborative Innovation Center of Biotherapy, Chengdu, 610041, China.

Activation of the TAK1 signalosome is crucial for mediating the innate immune response to pathogen invasion and is regulated by multiple layers of posttranslational modifications, including ubiquitination, SUMOylation, and phosphorylation; however, the underlying molecular mechanism is not fully understood. In this study, TRIM60 negatively regulated the formation and activation of the TAK1 signalosome. Deficiency of TRIM60 in macrophages led to enhanced MAPK and NF-κB activation, accompanied by elevated levels of proinflammatory cytokines but not IFN-I. Immunoprecipitation-mass spectrometry assays identified TAB2 as the target of TRIM60 for SUMOylation rather than ubiquitination, resulting in impaired formation of the TRAF6/TAB2/TAK1 complex and downstream MAPK and NF-κB pathways. The SUMOylation sites of TAB2 mediated by TRIM60 were identified as K329 and K562; substitution of these lysines with arginines abolished the SUMOylation of TAB2. In vivo experiments showed that TRIM60-deficient mice showed an elevated immune response to LPS-induced septic shock and L. monocytogenes infection. Our data reveal that SUMOylation of TAB2 mediated by TRIM60 is a novel mechanism for regulating the innate immune response, potentially paving the way for a new strategy to control antibacterial immune responses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41423-020-00564-wDOI Listing
November 2020

Carcinoembryonic Antigen: A Potential Biomarker to Evaluate the Severity and Prognosis of COVID-19.

Front Med (Lausanne) 2020 6;7:579543. Epub 2020 Oct 6.

Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Corona Virus Disease 2019 (COVID-19) has become a serious pandemic disease worldwide. Identification of biomarkers to predict severity and prognosis is urgently needed for early medical intervention due to high mortality of critical cases with COVID-19. This retrospective study aimed to indicate the values of carcinoembryonic antigen (CEA) in evaluating the severity and prognosis of COVID-19. We included 46 death cases from intensive care unit and 68 discharged cases from ordinary units with confirmed COVID-19 of Wuhan Jin Yin-tan Hospital from January 1 to March 22, 2020. Laboratory and radiologic data were analyzed retrospectively. All patients were followed up until April 10, 2020. COVID-19 patients in the death group had significantly higher CEA levels (ng/ml) than discharged group (14.80 ± 14.20 vs. 3.80 ± 2.43, < 0.001). The risk of COVID-19 death increased 1.317 times for each additional 1 ng/ml CEA level (OR = 1.317, 95% CI: 1.099-1.579). The standardized and weighted receiver operating characteristic curve (ROC) analysis adjusted to age, sex, and ferritin levels suggested that the area under the curve (AUC) of the serum CEA levels was 0.808 in discrimination between death cases and discharged cases with COVID-19 ( < 0.001). We found mortality of COVID-19 is associated with elevated CEA levels increased (HR = 1.023, 95% CI: 1.005-1.042), as well as age (HR = 1.050, 95% CI: 1.016-1.086) and ferritin levels (HR = 1.001, 95% CI: 1.001-1.002) by survival analysis of Cox regression model. Among discharged patients, CEA levels were significant lower in moderate cases compared to the severe and critical cases ( = 0.005; OR = 0.488, 95% CI: 0.294-0.808) from binary logistic regression analysis. The AUC of CEA levels was 0.79 in distinguishing moderate cases from discharged COVID-19 patients by standardized and weighted ROC analysis ( < 0.001). A positive correlation between CEA levels and CT scores existed in discharged patients (Correlation Coefficient: 0.687; < 0.001). Elevated CEA levels increased the risk of death from COVID-19 and CEA levels were related to CT scores of the discharged patients positively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fmed.2020.579543DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7573292PMC
October 2020

Interactions between microplastics and organic pollutants: Effects on toxicity, bioaccumulation, degradation, and transport.

Sci Total Environ 2020 Dec 21;748:142427. Epub 2020 Sep 21.

State Key Laboratory of Pollution Control and Resource Reuse, School of the Environment, Nanjing University, Nanjing 210023, China; International Institute for Environmental Studies, Nanjing 210023, China. Electronic address:

Microplastics (MPs), defined as particles with diameters <5 mm and including nanoplastics (NPs), with diameters <1 μm, are characterized by large specific surface areas and hydrophobicity. In aquatic and terrestrial environments, MPs interact with co-occurring organic pollutants through sorption and desorption, which alters the environmental behavior of the pollutants, such as their toxicity, bioaccumulation, degradation, and transport. In this review, we summarize the results of current studies of the interactions between MPs and organic contaminants, and focus on the different mechanisms and subsequent ecological risks of contaminant transfer among environmental media, MPs and organisms. The sorption/desorption of organic pollutants on/from MPs is discussed with respect to solution conditions and the properties of both the MPs and the pollutants. More importantly, the ability of MPs to alter the toxicity, bioaccumulation, degradation, and transport of organic pollutants through these interactions is considered as well. We then examine the interrelationships of the different environmental behaviors of MPs and organic pollutants and the roles played by environmental processes. Finally, we identify the remaining knowledge gaps that must be filled in further studies in order to accurately evaluate the environmental risks of MPs and their associated organic pollutants.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.scitotenv.2020.142427DOI Listing
December 2020

Comparison of actual and simulated tumoricidal effects induced by photodynamic therapy.

Photodiagnosis Photodyn Ther 2020 Dec 13;32:102060. Epub 2020 Oct 13.

Laser Medicine Laboratory, Institute of Biomedical Engineering, Chinese Academy of Medical Science, Peking Union Medical College, Tianjin, 300192, China. Electronic address:

Objectives: Numerous studies employ mathematical methods, such as Monte Carlo simulation, to predict the tumor killing effects of photodynamic therapy (PDT) by simulating optical propagation, photosensitizer distribution, and oxygen distribution. Whether these models faithfully reflect tumor killing is unknown, and model validation using tumor cross sections in these studies is usually insufficient to answer this question. To fill this gap in our knowledge, we employed a mouse model of breast cancer to determine the spatiotemporal effects of PDT using direct histopathological and biochemical analyses of whole tumors.

Methods: We prepared approximately 700 5-μm-thick serial sections of breast tumors of syngeneic mice treated with PDT employing the photosensitizer photocarcinorin (PsD-007, a second-generation photosensitizer developed in China). Three adjoining sections were subjected to hematoxylin and eosin staining to assess necrosis, the TUNEL assay to evaluate apoptosis, and CD31 staining to detect angiogenesis, respectively. We then generated a three-dimensional (3D) reconstruction of the tumor to evaluate these processes. We simultaneously used the Monte Carlo method to develop a model of light distribution throughout the tumor to evaluate the actual and simulated tumor killing effects induced by PDT.

Results: Tumor necrosis decreased exponentially as a function of distance from the source of illumination, while the distributions of apoptosis and neovascularization were independent of light distribution. Most apoptosis occurred in the lower layers (3000-4000 μm) of the tumor where the light intensity was too low to excite the photosensitizer. Neovascularization occurred at depths ranging from 2500 to 3500 μm. These analyses provided a 3D view of how a tumor is destroyed using PDT.

Conclusions: Although the optical distribution model predicted tumor necrosis caused by PDT, it was ineffective in predicting the sites of apoptosis and vascular destruction. Mathematical modeling is limited in its capabilities required to gain a comprehensive understanding of the spatiotemporal events associated with PDT. The mouse model developed here will serve as a platform for detailed direct histopathological, biochemical, and molecular genetic analyses of the effects of PDT, which will facilitate the development of optimized treatment strategies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pdpdt.2020.102060DOI Listing
December 2020

Microbial community and function in nitrogen transformation of ectopic fermentation bed system for pig manure composting.

Bioresour Technol 2021 Jan 24;319:124155. Epub 2020 Sep 24.

Agricultural Bio-resource Research Institute, Fujian Academy of Agriculture Sciences, Fuzhou 350003, China.

In this work, agricultural wastes were treated by composting in an ectopic fermentation bed system (EFBS) with a continuous nitrogen addition technique. With decreasing of NH-N concentration and increasing of NO-N concentration were observed, and activities of protease, urease and nitrate reductase changed significantly during the fermentation process. To elucidate the key microbes and their function in nitrogen-transforming, microbial diversity and clusters of orthologous groups (COGs) in composting materials were evaluated using metagenomic technology. Comparing with ammonification, the COGs involved in nitrification and denitrification were predominant in the composts. The correlation heatmap revealed that Streptomyces predominant in ammonification was significantly affected by contents of N, NH-N and NO-N. Meanwhile, ammonia-oxidizing archaea (AOA) had a positive relationship with moisture. The most abundant genera in denitrification had positive relationships with N and NO-N. The results indicated that EFBS had functionally diverse microbes and COGs for NH removal.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.biortech.2020.124155DOI Listing
January 2021

An Overview on Noble Metal (Group VIII)-based Heterogeneous Electrocatalysts for Nitrogen Reduction Reaction.

Chem Asian J 2020 Dec 25;15(24):4131-4152. Epub 2020 Nov 25.

Key Laboratory of Carbon Materials of Zhejiang Province, College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, 325027, P. R. China.

The typically the Haber-Bosch process of nitrogen (N ) reduction to ammonia (NH ) production, expends a lot of energy, resulting in severe environmental issues. Electro-catalytic N reduction to NH formation by renewable resources is one of the effective ways to settle the issue. However, the electro-catalytic performances and selectivity of catalysts for electrochemical nitrogen reduction reaction (NRR) are very low. Therefore, it is of great significance to develop more efficient electro-catalysts to satisfy the needs of practical use. Among the reported catalysts, those based on Group VIII noble metals heterogeneous catalysts display excellent NRR activities and high selectivity because of their good conductivity, rich active surface area, unfilled d-orbitals, and the abilities with easy adsorption of reactants and stable reaction intermediates. Herein, we will introduce the progress of Group VIII precious metals heterogeneous catalysts applied in the electrocatalytic N reduction reaction. Then single precious metal electrocatalysts, precious metal alloy electrocatalysts, heterojunction structure electrocatalysts, and precious metal compounds based on the strategies of morphology engineering, crystal facet engineering, defect engineering, heteroatom doping, and synergetic interface engineering will be discussed. Finally, the challenges and prospects of the NH synthesis have been put forward. In the review, we will provide helpful direction to the development of effective electro-catalysts for catalytic N reduction reaction.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/asia.202000969DOI Listing
December 2020

Diagnostic value of the enhancement intensity and enhancement pattern of CESM to benign and malignant breast lesions.

Medicine (Baltimore) 2020 Sep;99(37):e22097

Department of Radiology, Yantai Yuhuangding Hospital, Affiliated Hospital of Qingdao University.

This study aimed to improve the diagnostic accuracy of breast diseases by combining breast imaging-reporting and data system (BI-RADS) with the enhancement intensity and pattern of contrast-enhanced spectral mammography (CESM) (this combination of BI-RADS and CESM was designated as BaC).BI-RADS was used to evaluate low-energy CESM images. Spearman nonparametric correlation analysis was performed to analyze the correlation between the enhancement intensity of CESM subtraction images and the pathological results. Odds ratio (OR) values were calculated to determine whether the enhancement pattern of CESM subtraction images is a risk factor for benign and malignant lesions. The diagnostic efficacies of BI-RADS, CESM, and BaC scores for benign and malignant breast diseases were analyzed using the receiver operating characteristic (ROC) curve.Lesions with a high enhancement intensity were more likely to be malignant than those with low enhancement intensity. Lesions with heterogeneous enhancement tended to be malignant, whereas those with homogeneous enhancement tended to be benign. No significant correlation was observed between ring enhancement and the benignity or malignancy of lesions. The area under the ROC curve of BaC was higher than that of BI-RADS or CESM, and the difference was statistically significant.The diagnostic efficacy of BI-RADS combined with CESM enhancement was superior to that of either method alone.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000022097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489654PMC
September 2020

A rare case of the pancreas with heterotopic gastric mucosa detected by EUS (with video).

Endosc Ultrasound 2020 Nov-Dec;9(6):410-412

Department of Digestive Diseases, The PLA General Hospital, Beijing, China.

Pancreas with heterotopic gastric mucosa is a rare congenital malformation and hardly be detected.In the embryonic stages, primitive gut, including foregut, midgut and hindgut, originated in the gastrula endoderm. Stomach and pancreas were stemed from the ending of foregut. When abnormal differentiation occurred, pancreatic tissue was usually ectopic to the stomach, but heterotopic gastric mucosa of the pancreas was rare. This malformation was usually confirmed by post-operative pathology. We report a case of congenital malformation of heterotopic gastric mucosa of pancreas detected by EUS and contrast enhanced EUS. The manifestations in EUS are different from the pancreatic cyst lesion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4103/eus.eus_19_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811713PMC
September 2020

The crystal structure of Atg18 reveals a new binding site for Atg2 in Saccharomyces cerevisiae.

Cell Mol Life Sci 2021 Mar 18;78(5):2131-2143. Epub 2020 Aug 18.

Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, College of Life Sciences, Sichuan University, Chengdu, China.

Macroautophagy (hereafter referred to as autophagy) is a highly conserved catabolic eukaryotic pathway that is critical for stress responses and homeostasis. Atg18, one of the core proteins involved in autophagy, belongs to the PROPPIN family and is composed of seven WD40 repeats. Together with Atg2, Atg18 participates in the elongation of phagophores and the recycling of Atg9 in yeast. Despite extensive studies on the PROPPIN family, the structure of Atg18 from Saccharomyces cerevisiae has not been determined. Here, we report the structure of ScAtg18 at a resolution of 2.8 Å. Based on bioinformatics and structural analysis, we found that the 7AB loop of ScAtg18 is extended in Atg18, in comparison to other members of the PROPPIN family. Genetic analysis revealed that the 7AB loop of ScAtg18 is required for autophagy. Biochemical and biophysical experiments indicated that the 7AB loop of ScAtg18 is critical for interaction with ScAtg2 and the recruitment of ScAtg2 to the autophagy-initiating site. Collectively, our results show that the 7AB loop of ScAtg18 is a new binding site for Atg2 and is of functional importance to autophagy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00018-020-03621-9DOI Listing
March 2021

Correction: FTSJ1 regulates tRNA 2'-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression.

Cell Death Dis 2020 Jun 3;11(6):418. Epub 2020 Jun 3.

School of Public Health, Guangdong Key Laboratory for Genome Stability & Disease Prevention, Carson Cancer Center, Shenzhen University Health Science Center, Shenzhen, 518055, China.

The original version of this article contained an error in the spelling of the author Yuchen Chen, which was incorrectly given as Yuhuan Chen. This has now been corrected in both the PDF and HTML versions of the article.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-2623-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266812PMC
June 2020

LncRNA BRCAT54 inhibits the tumorigenesis of non-small cell lung cancer by binding to RPS9 to transcriptionally regulate JAK-STAT and calcium pathway genes.

Carcinogenesis 2021 Feb;42(1):80-92

School of Public Health, Shenzhen University Health Science Center, Shenzhen, China.

Objectives: Increasing evidence suggest that long non-coding RNAs (lncRNAs) play critical roles in cancers. However, the expression pattern and underlying mechanisms of lncRNAs in non-small cell lung cancer (NSCLC) remain incompletely understood. This study aimed to elucidate the functions and molecular mechanisms of a certain lncRNA in NSCLC.

Methods: LncRNA microarray was performed to identify differential expressed lncRNAs between pre- and postoperation plasma in NSCLC patients. The expression level of candidate lncRNA in NSCLC tissues, plasma and cells was determined by quantitative real-time PCR (qRT-PCR) and in situ hybridization. The functional roles of lncRNA were assessed in vitro and in vivo. Furthermore, RNA pull-down, RNA immunoprecipitation, microarray, qRT-PCR and rescue assays were conducted to explore the mechanism action of lncRNA in NSCLC cells.

Results: We identified a novel lncRNA (BRCAT54), which was significantly upregulated in preoperative plasma, NSCLC tissues and NSCLC cells, and its higher expression was associated with better prognosis in patients with NSCLC. Overexpression of BRCAT54 inhibited proliferation, migration and activated apoptosis in NSCLC cells. Conversely, knockdown of BRCAT54 reversed the suppressive effects of BRCAT54. Moreover, overexpression of BRCAT54 repressed NSCLC cell growth in vivo. Mechanistically, BRCAT54 directly bound to RPS9. Knockdown of RPS9 substantially reversed the promoting effects of si-BRCAT54 on cell proliferation and enhanced the inhibitive effect of si-BRCAT54 on BRCAT54 expression. In addition, silencing of RPS9 activated JAK-STAT pathway and suppressed calcium signaling pathway gene expressions.

Conclusion: This study identified BRCAT54 as a tumor suppressor in NSCLC. Targeting the BRCAT54 and RPS9 feedback loop might be a novel therapeutic strategy for NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/carcin/bgaa051DOI Listing
February 2021

Analysis of factors related to prognosis and death of fish bile poisoning in China: A retrospective study.

Basic Clin Pharmacol Toxicol 2020 Nov 17;127(5):419-428. Epub 2020 Jun 17.

Department of Forensic Science, School of Basic Medical Science, Central South University, Changsha, China.

Fish bile has long been considered to have therapeutic benefits in folk medicine in some Asian countries. However, poisoning incidents and even death sporadically occurred when people consumed fish bile. Herein, we summarize the main characteristics of fish bile poisoning in China including clinical symptoms, treatment strategies and factors being associated with death and affecting prognosis, hoping to provide a reference for the diagnosis and treatment of fish bile poisoning, as well as forensic identification of death cases induced by fish bile poisoning. We suggest that the health authorities should make an effort to enhance people's awareness of the safety of traditional medicine like fish bile so as to reduce the incidence of adverse events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bcpt.13447DOI Listing
November 2020

Deep proteome profiling of SW837 cells treated by photodynamic therapy (PDT) reveals the underlying mechanisms of metronomic and acute PDTs.

Photodiagnosis Photodyn Ther 2020 Sep 11;31:101809. Epub 2020 May 11.

Laboratory of Laser Medicine, Chinese Academy of Medical Sciences & Peking Union Medical College Institute of Biomedical Engineering, 236 Baidi Road, Nankai District, Tianjin 300192, China.

Aim: Metronomic photodynamic therapy (mPDT) with a longer irradiation time and lower energy compared with acute (or classic) photodynamic therapy (aPDT) is a more effective treatment than aPDT for tumor cells, especially colorectal cancer. However, the underlying mechanisms of the superior effects of mPDT are unknown.

Methods: we used SWATH-MS (sequential window acquisition of all theoretical mass spectra) to identify differentially expressed proteins (DEPs) specific to aPDT (conventional fluence rate, 20 mW/cm, 4 min 10 s), mPDT (metronomic fluence rate, 0.4 mW/cm, 3.5 h), and control groups of SW837 cells. The photosensitizer used in both PDT methods was aminolevulinic acid which were incubated with the cells before irradiation.

Results: A total of 6805 proteins were identified in the three groups of SW837 cells. aPDT induced 333 DEPs and mPDT induced 1716 DEPs compared with the control. We identified 185 common DEPs in the two PDT groups, 148 different DEPs in the aPDT group, and 1531 different DEPs in the mPDT group. Most of the 185 common DEPs were involved in the extracellular component, participated in the processes of vesicle transport and secretion, binding, and hydrolase/catalytic activity. They were also involved in PI3K-Akt, cGMP-PKG, RAS, and aAMP signaling pathways. In addition, the 1531 different DEPs in the mPDT group participated in similar processes and molecular functions, but in a more complex manner than those in the aPDT group.

Conclusion: our proteome data suggest that mPDT has a complex tumor destruction mechanism with more involved proteins compared with aPDT, which may explain the better tumor killing effect of mPDT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pdpdt.2020.101809DOI Listing
September 2020

An asymmetric end-capping strategy enables a new non-fullerene acceptor for organic solar cells with efficiency over 10.

Chem Commun (Camb) 2020 Jun 12;56(48):6531-6534. Epub 2020 May 12.

Chongqing Institute of Green and Intelligent Technology, Chinese Academy of Sciences, Chongqing, 400714, China.

Two different terminal groups, rhodanine-flanked benzo[c][1,2,5]thiadiazole (BR) and 2-(5,6-difluoro-3-oxo-2,3-dihydro-1H-inden-1-ylidene)malononitrile (IM2F), were connected to an indaceno[1,2-b:5,6-b']dithiophene (IDT) core to construct a new non-fullerene acceptor (IDTBF). Solar cells based on this acceptor exhibited promising photovoltaic performances with a power conversion efficiency (PCE) of up to 10.43%.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d0cc01739fDOI Listing
June 2020

FTSJ1 regulates tRNA 2'-O-methyladenosine modification and suppresses the malignancy of NSCLC via inhibiting DRAM1 expression.

Cell Death Dis 2020 05 11;11(5):348. Epub 2020 May 11.

School of Public Health, Guangdong Key Laboratory for Genome Stability & Disease Prevention, Carson Cancer Center, Shenzhen University Health Science Center, Shenzhen, 518055, China.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer mortality worldwide. The mechanisms underlying NSCLC tumorigenesis are incompletely understood. Transfer RNA (tRNA) modification is emerging as a novel regulatory mechanism for carcinogenesis. However, the role of tRNA modification in NSCLC remains obscure. In this study, HPLC/MS assay was used to quantify tRNA modification levels in NSCLC tissues and cells. tRNA-modifying enzyme genes were identified by comparative genomics and validated by qRT-PCR analysis. The biological functions of tRNA-modifying gene in NSCLC were investigated in vitro and in vivo. The mechanisms of tRNA-modifying gene in NSCLC were explored by RNA-seq, qRT-PCR, and rescue assays. The results showed that a total of 18 types of tRNA modifications and up to seven tRNA-modifying genes were significantly downregulated in NSCLC tumor tissues compared with that in normal tissues, with the 2'-O-methyladenosine (Am) modification displaying the lowest level in tumor tissues. Loss- and gain-of-function assays revealed that the amount of Am in tRNAs was significantly associated with expression levels of FTSJ1, which was also downregulated in NSCLC tissues and cells. Upregulation of FTSJ1 inhibited proliferation, migration, and promoted apoptosis of NSCLC cells in vitro. Silencing of FTSJ1 resulted in the opposite effects. In vivo assay confirmed that overexpression of FTSJ1 significantly suppressed the growth of NSCLC cells. Mechanistically, overexpression of FTSJ1 led to a decreased expression of DRAM1. Whereas knockdown of FTSJ1 resulted in an increased expression of DRAM1. Furthermore, silencing of DRAM1 substantially augmented the antitumor effect of FTSJ1 on NSCLC cells. Our findings suggested an important mechanism of tRNA modifications in NSCLC and demonstrated novel roles of FTSJ1 as both tRNA Am modifier and tumor suppressor in NSCLC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-2525-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214438PMC
May 2020

The human mitochondrial 12S rRNA mC methyltransferase METTL15 is required for mitochondrial function.

J Biol Chem 2020 06 5;295(25):8505-8513. Epub 2020 May 5.

Division of Newborn Medicine and Epigenetics Program, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts, USA

Mitochondrial DNA gene expression is coordinately regulated both pre- and post-transcriptionally, and its perturbation can lead to human pathologies. Mitochondrial rRNAs (mt-rRNAs) undergo a series of nucleotide modifications after release from polycistronic mitochondrial RNA precursors, which is essential for mitochondrial ribosomal biogenesis. Cytosine -methylation (mC) at position 839 (mC839) of the 12S small subunit mt-rRNA was identified decades ago; however, its biogenesis and function have not been elucidated in detail. Here, using several approaches, including immunofluorescence, RNA immunoprecipitation and methylation assays, and bisulfite mapping, we demonstrate that human methyltransferase-like 15 (METTL15), encoded by a nuclear gene, is responsible for 12S mt-rRNA methylation at mC839 both and We tracked the evolutionary history of RNA mC methyltransferases and identified a difference in substrate preference between METTL15 and its bacterial ortholog rsmH. Additionally, unlike the very modest impact of a loss of mC methylation in bacterial small subunit rRNA on the ribosome, we found that METTL15 depletion results in impaired translation of mitochondrial protein-coding mRNAs and decreases mitochondrial respiration capacity. Our findings reveal that human METTL15 is required for mitochondrial function, delineate the evolution of methyltransferase substrate specificities and modification patterns in rRNA, and highlight a differential impact of mC methylation on prokaryotic ribosomes and eukaryotic mitochondrial ribosomes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1074/jbc.RA119.012127DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307190PMC
June 2020

Assessment, Distribution and Regional Geochemical Baseline of Heavy Metals in Soils of Densely Populated Area: A Case Study.

Int J Environ Res Public Health 2020 03 27;17(7). Epub 2020 Mar 27.

School of Resources and Civil Engineering, Suzhou University, Suzhou 234000, China.

To understand the content, pollution, distribution and source and to establish a geochemical baseline of heavy metal elements in soil under the influence of high-density population, the concentrations of heavy metal elements Cr, Mn, Co, Ni, Cu, Zn, As, Cd, Hg, Pb and Fe were determined in 23 soil samples in Suzhou University, and geo-accumulation index, enrichment factor, principal component analysis, spatial analysis and regression analysis were completed. The results showed the following: The elements Cu and As were slightly polluted, while the other heavy metal elements were not. The elements Cd, Cu, Ni and As in soils were mainly caused by agricultural activities of chemical fertilizer, whereas the elements Zn and Hg were impacted by the chemicals and batteries. The heavy metal elements in the north were lower than in the south of the campus, as a whole. The enrichment of elements Cu, As and Cd was caused by the east-west river on the campus, and the enrichment of the elements Mn, Ni and Zn was induced by the reservoir. Biochemical experiments and vehicle parking influenced the spatial enrichment of Cr, Co and Pb, while domestic waste led to the spatial differentiation of Hg concentrations. The regression curve between heavy metal elements and Fe was established, and the background values of the heavy metals Cr, Mn, Co, Ni, Cu, Zn, As, Cd, Hg and Pb are 50.90, 489.37, 11.76, 37.74, 55.70, 58.22, 20.07, 0.09, 0.08 and 24.13 mg/kg, respectively.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijerph17072269DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7177485PMC
March 2020

Structural and functional insight into the effect of AFF4 dimerization on activation of HIV-1 proviral transcription.

Cell Discov 2020 18;6. Epub 2020 Feb 18.

1Department of Urology, State Key Laboratory of Biotherapy, West China Hospital, College of Life Sciences, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041 China.

Super elongation complex (SEC) is a positive regulator of RNA polymerase II, which is required for HIV-1 proviral transcription. AFF1/4 is the scaffold protein that recruits other components of SEC and forms dimer depending on its THD domain (TPRL with Handle Region Dimerization Domain). Here we report the crystal structure of the human AFF4-THD at the resolution of 2.4 Å. The α4, α5, and α6 of one AFF4-THD mediate the formation of a dimer and pack tightly against the equivalent part of the second molecule in the dimer of AFF-THD. Mutagenesis analysis revealed that single mutations of either Phe1014 or Tyr1096 of AFF4 to alanine impair the formation of the AFF4 dimer. In addition, transactivation assay also indicated that Phe1014 and Tyr1096 of AFF4 are critical to the transactivation activity of AFF4. Interestingly, the corresponding residues Phe1063 and Tyr1145 in AFF1 have an effect on the transactivation of HIV-1 provirus. However, such mutations of AFF1/4 have no effect on the interaction of AFF1/4 with other subunits of the SEC. Together, our data demonstrated that the dimerization of AFF1/4 is essential to transactivation of HIV-1 provirus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41421-020-0142-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7026398PMC
February 2020

[Role of rate-limiting step of mevalonate pathway in improving lycopene production in Escherichia coli].

Sheng Wu Gong Cheng Xue Bao 2020 Jan;36(1):77-89

Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.

The introduction of the mevalonate pathway (MVA pathway) in recombinant Escherichia coli can improve the synthesis of terpenoids. But the imbalance expression of MVA pathway genes and accumulation of intermediates inhibit cell growth and terpenoids production. In this study, each gene of MVA pathway and key genes of lycopene synthesis pathway were cloned in plasmid to express in the recombinant E. coli LYC103 with optimizing the expression of the key genes of the 2-methyl-D-erythritol-4-phosphate pathway (MEP pathway), chromosome recombinant MVA pathway and the lycopene synthesis pathway. The results showed that the overexpression of ispA, crtE, mvaK1, idi and mvaD genes did not affect the cell growth, while lycopene production increased by 13.5%, 16.5%, 17.95%, 33.7% and 61.1% respectively, indicating that these genes may be the rate-limiting steps for the synthesis of lycopene. mvaK1, mvaK2, mvaD of MVA pathway were the rate-limiting steps and were in an operon. The mvaK1, mvaK2, mvaD operon was regulated by mRS (mRNA stabilizing region) library in front of mvaK1, obtaining strain LYC104. Lycopene yield of LYC104 was doubled and cell growth was increased by 32% compared with the control strain LYC103. CRISPR-cas9 technology was used to integrate idi into chromosome at lacZ site to obtain LYC105 strain. Cell growth of LYC105 was increased by 147% and lycopene yield was increased by 2.28 times compared with that of LYC103. In this study, each gene of lycopene synthesis pathway was expressed in plasmid to certify the rate-limiting gene based on the complete MVA pathway on the chromosome. Then the rate-limiting gene was integrated in chromosome with homologous recombination to release the rate-limiting, which providing a new strategy for the construction of high-yield strains for metabolic engineering.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.13345/j.cjb.190189DOI Listing
January 2020