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OBJECTIVES: This study aimed to analyze the possible role of rDNA copy number variation in the association between hexavalent chromium [Cr (VI)] exposure and semen quality in semen donors and further confirm this association in mice. METHODS: In this cross-sectional study, whole blood and semen samples were collected from 155 semen donors in the Zhejiang Human Sperm Bank from January 1st to April 31st, 2021. Adult C57BL/6â¯J male mice were treated with different doses of Cr (VI) (0, 10, or 15â¯mg/kg b.w./day). Semen quality, including semen volume, total spermatozoa count, sperm concentration, progressive motility, and total motility, were analyzed according to the WHO laboratory manual. Cr concentration was detected using inductively coupled plasma mass spectrometry. The rDNA copy number was measured using qPCR. RESULTS: In semen donors, whole blood Cr concentration was negatively associated with semen concentration and total sperm counts. Semen 5â¯S and 45â¯S rDNA copy numbers were negatively associated with whole blood Cr concentration and whole blood 5.8â¯S rDNA copy number was negatively associated with semen Cr concentration. In mice, Cr (VI) damaged testicular tissue, decreased semen quality, and caused rDNA copy number variation. Semen quality was related to the rDNA copy number in whole blood, testicular tissue, and semen samples in mice. CONCLUSION: Cr (VI) was associated with decreased semen quality in semen donors and mice. Our findings suggest an in-depth analysis of the role of the rDNA copy number variation in the Cr (VI)-induced impairment of semen quality.
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Cromo , Variaciones en el Número de Copia de ADN , Análisis de Semen , Masculino , Animales , Humanos , Variaciones en el Número de Copia de ADN/efectos de los fármacos , Ratones , Análisis de Semen/veterinaria , Adulto , Cromo/toxicidad , Estudios Transversales , Ratones Endogámicos C57BL , ADN Ribosómico/genética , Semen/efectos de los fármacos , Recuento de Espermatozoides , Espermatozoides/efectos de los fármacosRESUMEN
Occupational silica exposure caused a serious disease burden of silicosis. There is currently a lack of sensitive and effective biomarkers for silicosis, and the pathogenesis of silicosis is unclear. Exosomes were significant in the pathogenesis of silicosis, and our study was carried out from exosomal proteomics and cytokine analysis. Firstly, the plasma levels of cytokines were detected using a Luminex multiplex assay, and the results indicated that the plasma levels of TNF-α, IL-6, CCL2, CXCL10, and PDGF-AB were significantly higher in silicosis patients than in silica-exposed workers and controls (p < 0.05). After correlation analysis, the plasma levels of cytokines were positively correlated with exosomal protein concentration. Secondly, data-independent acquisition (DIA) was performed on plasma-derived exosomes in the screening population, which identified 88, 151, 293, and 53 differentially expressed proteins (DEPs) in exposure/control, silicosis/control, silicosis/exposure, and silicosis stage â ¢/silicosis stage â groups respectively. After parallel reaction monitoring (PRM) in an independent verification population, the results indicated that the changing trend of 15 DEPs was coincident in screening and verification results. The result of correlation analysis indicated that the plasma level of TNF-α was negatively correlated with the expression of exosomal DSP, KRT78, SERPINB12, and CALML5. The AUC of combined determination of TNF-α and CALML5 reached 0.900, with a sensitivity of 0.714 and a specificity of 0.933. Overall, our study revealed the exosomal proteomic profiling of silicosis patients, silica-exposed workers, and controls, indicating that exosomes were significant in the pathogenesis of silicosis. It also revealed that the combined of the plasma levels of cytokines and the expression of exosomal DEPs could increase determination efficiency. This study provided directions for the development of silicosis biomarkers and a scientific basis for the pathogenesis research of silicosis in the future.
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Our previous study identified the potential of SEMA4B methylation level as a biomarker for hexavalent chromium [Cr(VI)] exposure. This study aimed to investigate the role of the SEMA4B gene in Cr(VI)-mediated malignant transformation of human bronchial epithelial (BEAS-2B) cells. In our population survey of workers, the geometric mean [95% confidence intervals (CIs)] of Cr in blood was 3.80 (0.42, 26.56) µg/L. Following treatment with various doses of Cr(VI), it was found that 0.5 µM had negligible effects on the cell viability of BEAS-2B cells. The expression of SEMA4B was observed to decrease in BEAS-2B cells after 7 days of treatment with 0.5 µM Cr(VI), and this downregulation continued with increasing passages of Cr(VI) treatment. Chronic exposure to 0.5 µM Cr(VI) enhanced the anchorage-independent growth ability of BEAS-2B cells. Furthermore, the use of a methylation inhibitor suppressed the Cr(VI)-mediated anchorage-independent growth in BEAS-2B cells. Considering that Cr levels exceeding 0.5 µM can be found in human blood due to occupational exposure, the results suggested a potential carcinogenic risk associated with occupational Cr(VI) exposure through the promotion of malignant transformation. The in vitro study further demonstrated that Cr(VI) exposure might inhibit the expression of the SEMA4B gene to promote the malignant transformation of BEAS-2B cells.
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Flavonoids are a class of secondary metabolites widely distributed in plants. Regiospecific modification by methylation and glycosylation determines flavonoid diversity. A rare flavone glycoside, diosmin (luteolin-4'-methoxyl-7-O-glucosyl-rhamnoside), occurs in Chrysanthemum indicum. How Chrysanthemum plants evolve new biosynthetic capacities remains elusive. Here, we assemble a 3.11-Gb high-quality C. indicum genome with a contig N50 value of 4.39 Mb and annotate 50,606 protein-coding genes. One (CiCOMT10) of the tandemly repeated O-methyltransferase genes undergoes neofunctionalization, preferentially transferring the methyl group to the 4'-hydroxyl group of luteolin with ortho-substituents to form diosmetin. In addition, CiUGT11 (UGT88B3) specifically glucosylates 7-OH group of diosmetin. Next, we construct a one-pot cascade biocatalyst system by combining CiCOMT10, CiUGT11, and our previously identified rhamnosyltransferase, effectively producing diosmin with over 80% conversion from luteolin. This study clarifies the role of transferases in flavonoid diversity and provides important gene elements essential for producing rare flavone.
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Chrysanthemum , Diosmina , Flavonas , Metiltransferasas/genética , Luteolina , Glucosiltransferasas/genética , Chrysanthemum/genética , Genómica , FlavonoidesRESUMEN
Objective@#To explore the changes in ribosomal DNA copy number in peripheral blood among patients with pneumoconiosis and its influencing factors, so as to provide insights into prevention and treatment of pneumoconiosis.@*Methods@#Eighty-eight patients with pneumoconiosis who visited a designated hospital and 71 community residents with no history of pneumoconiosis or dust exposure were selected as the pneumoconiosis group and control group, and age, smoking history, drinking history and cumulative years of exposure to dust were collected through questionnaire surveys. The copy number of 45S rDNA and 5S rDNA was detected using real-time fluorescence quantitative PCR, and the differences between the two groups were compared. Factors affecting the copy number of 45S rDNA and 5S rDNA were identified by a multiple linear regression model.@*Results@#The pneumoconiosis group had a median age of 56.00 (interquartile range, 15.25) and a mean cumulative dust exposure duration of (12.40±8.08) years, with 56.82% smoking and 62.50% drinking. The control group had a median age of 64.00 (interquartile range, 37.00) years, with 32.39% smoking and 26.76% drinking. The median copy number of 45S rDNA in the pneumoconiosis group was 1.29 (interquartile range, 0.59), which was lower than 2.10 (interquartile range, 1.88) in the control group; the median copy number of 5S rDNA in the pneumoconiosis group was 5.33 (interquartile range, 0.85), which was higher than 4.66 (1.34) in the control group (both P<0.05). Multiple linear regression analysis identified age (β=-0.034) and pneumoconiosis (β=-1.595) as factors affecting 45S rDNA copy number, age (β=-0.013) as a factor affecting 5S rDNA copy number, and age (β=0.018) as a factor affecting 5S rDNA copy number in the pneumoconiosis group (all P<0.05).@*Conclusions@#Compared with community residents with no history of pneumoconiosis or dust exposure, the copy number of 45S rDNA in peripheral blood among patients with pneumoconiosis is reduced and the copy number of 5S rDNA is increased.
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BACKGROUND: Several studies have provided evidence about adverse pregnancy outcomes of nurses involved in occupational exposure. However, the pregnancy outcomes among nurses in middle-income countries are not well demonstrated. The main aim of this study is to present the prevalence and influencing factors of pregnancy outcomes among female nurses in China. METHODS: We included 2243 non-nurse health care workers, and 4230 nurses in this national cross-sectional study in China. Information on occupational exposures and pregnancy outcomes was collected using a face-to-face investigation. Odds ratios (ORs) were estimated through logistic regression. RESULTS: The proportion of threatened abortion, spontaneous abortion, and stillbirth of female nurses was 2.6%, 7%, and 2.1%, respectively. We found an increased risk of threatened abortion among nurses with overtime work (OR = 1.719, 95% CI 1.158-2.550). The risk of threatened abortion and spontaneous abortion was elevated among nurses handling disinfectant (OR = 2.293 and 1.63, respectively). We found a nearly twofold increased risk of premature birth (OR = 2.169, 95% CI 1.36-3.459) among nurses handling anti-cancer drugs. CONCLUSIONS: Our findings suggested that maternal occupational exposures might be associated with the risk of adverse pregnancy outcomes among female nurses in China. We recommend that policy-markers and hospital managers work together to reduce exposure to occupational hazards and improve pregnancy outcomes among female nurses.
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Exposición Materna , Enfermería , Exposición Profesional , Femenino , Humanos , Embarazo , Aborto Espontáneo/epidemiología , Aborto Espontáneo/etiología , Amenaza de Aborto , Estudios Transversales , Pueblos del Este de Asia/estadística & datos numéricos , Exposición Profesional/efectos adversos , Exposición Profesional/estadística & datos numéricos , Resultado del Embarazo/epidemiología , China , Enfermería/estadística & datos numéricos , Exposición Materna/efectos adversos , Exposición Materna/estadística & datos numéricosRESUMEN
BACKGROUND: Ribosomal DNA (rDNA) is the most abundant and important housekeeping gene in the cell. It usually acted as DNA damage sensor in DNA damage reaction. Gastric cancer (GC) as a tumor with high morbidity and mortality, it is hard to diagnosis in an early stage. METHODS: In this study, we collected and test the copy number of rDNA in blood sample of 42 GC patients and 56 healthy controls (HC) to explore the relationship between rDNA and GC. Besides, we make a correlation between the copy number of rDNA and ten biomarkers (CYFR21-1, CA15-3, CA72-4, NSE, CEA, CA125, ProGRP, AFP, SCC, CA19-9). RESULTS: The copy number of 18 S, 5.8 S, 28 S rDNA in GC is less than HC and 5 S is more than HC in their blood sample. And the expression of H-cox-1 and ND1 in GC is higher than HC in blood sample. it shows the expression of CA15-3 is related to ND1 and H-cox-1. CONCLUSION: We found for the first time the changes of rDNA and mtDNA expression in the blood of patients with gastric cancer. All these finding suggests rDNA may have potential in diagnosing GC.
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Antígenos de Carbohidratos Asociados a Tumores , Neoplasias Gástricas , Humanos , Biomarcadores de Tumor/genética , Neoplasias Gástricas/patología , Variaciones en el Número de Copia de ADN/genética , Antígeno Carcinoembrionario , ADN Ribosómico/genética , Mucina-1RESUMEN
The carcinogenicity of hexavalent chromium [Cr(VI)] and its compounds has been widely recognized, yet the mechanism of genetic damage is still not fully understood. The ribosomal DNA (rDNA) copy number is recently considered a potential marker of cancer-associated stress. To investigate the roles of rDNA copy number variation (CNV) in DNA damage responses (DDRs) induced by Cr(VI) and the potential mechanism from nucleolar protein HRAS, a cross-sectional study in Cr(â ¥)-exposed workers and an in vitro experiment using HeLa cells were conducted. Our results showed increased levels of rDNA CNV, DDRs, and HRAS expression in Cr(VI)-exposed workers. Generalized linear regression analyses showed that Cr(VI) exposure was significantly positively associated with increased levels of rDNA CNV, DDRs, and HRAS expression in Cr(VI)-exposed workers. Moreover, there were pairwise associations between rDNA CNV, DDRs, and HRAS levels. Mediation analyses found that rDNA CNV significantly mediated the association between Cr(VI) exposure and DDRs. The in vitro experiments further confirmed that Cr(VI) treatment induced increased levels of rDNA CNV, DDRs, and HRAS expression in HeLa cells. Cr(VI)-induced rDNA CNV, ATM activation, and apoptosis damage were then strongly enhanced by HRAS depletion with siRNA in vitro, suggesting the important role of HRAS in CNV and DDRs caused by Cr(VI). The combined results of the human and cell line studies indicated that Cr(VI) exposure might enhance rDNA CNV by regulation of HRAS expression, which leads to Cr(VI)-induced genetic damage.
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Variaciones en el Número de Copia de ADN , Proteínas Nucleares , Humanos , Proteínas Nucleares/metabolismo , Células HeLa , Daño del ADN , Estudios Transversales , Cromo/toxicidad , Cromo/metabolismo , ADN Ribosómico , Proteínas Proto-Oncogénicas p21(ras)/metabolismoRESUMEN
Chrysanthemum indicum L. is a valuable medicinal plant with diploid and tetraploid forms that are widely distributed in central and southern China, and it contains abundant volatile organic compounds (VOCs). Despite the discovery of some terpene synthase (TPS) in C. indicum (i.e., CiTPS) in previous studies, many TPSs and their corresponding terpene biosynthesis pathways have yet to be discovered. In the present study, terpenoid VOCs in different tissues from two cytotypes of C. indicum were analyzed. We identified 52 types of terpenoid VOCs and systematically investigated the content and distribution of these compounds in various tissues. The two cytotypes of C. indicum exhibited different volatile terpenoid profiles. The content of monoterpenes and sesquiterpenes in the two cytotypes showed an opposite trend. In addition, four full-length candidate TPSs (named CiTPS5-8) were cloned from Ci-GD4x, and their homologous TPS genes were screened based on the genome data of Ci-HB2x. These eight TPSs displayed various tissue expression patterns and were discovered to produce 22 terpenoids, 5 of which are monoterpenes and 17 are sesquiterpenes. We further proposed corresponding terpene synthesis pathways, which can enable the establishment of an understanding of the volatile terpenoid profiles of C. indicum with different cytotypes. This knowledge may provide a further understanding of germplasm in C. indicum and may be useful for biotechnology applications of Chrysanthemum plants.
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Transferasas Alquil y Aril , Chrysanthemum , Sesquiterpenos , Compuestos Orgánicos Volátiles , Terpenos/metabolismo , Compuestos Orgánicos Volátiles/metabolismo , Diploidia , Tetraploidía , Chrysanthemum/genética , Chrysanthemum/metabolismo , Monoterpenos/metabolismo , Transferasas Alquil y Aril/genéticaRESUMEN
Objective@#To investigate the effect of ribosomal DNA (rDNA) copy number variation caused by hexavalent chromium exposure on DNA damage response in different cell lines, so as to provide insights into the involvement of hexavalent chromium-induced rDNA copy number variation in DNA damage responses. @*@#Methods Human lung epithelial BEAS-2B cells and human embryonic lung MRC-5 cells were treated with 2 μmol/L potassium dichromate for 24 hours, and then cells were transferred to fresh media for further incubation, while cells treated with the same volume of phosphate buffer solution served as controls. Cells treated with potassium dichromate for 24 hours, and 3 and 7 days post-detoxification, were harvested, and rDNA copy number was quantified in cells using a quantitative fluorescent real-time PCR assay. Cell cycle, apoptosis and DNA damage were detected using a Muse cell analyzer, and the DNA damage was evaluated with the proportion of ataxia telangiectasia-mutated (ATM) gene activation, proportion of double-strand DNA breaks and the percentage of the H2A.X variant histone phosphorylatio.@*@# Results The 45S and 5S rDNA copy numbers of were significantly higher in MRC-5 cells than in BEAS-2B cells [(1.54±0.26) vs. (1.02±0.18), P<0.05; (6.97±1.07) vs. (3.00±0.15), P<0.05]. The 45S rDNA copy number was lower in MRC-5 cells 3 days post-detoxification (0.80±0.04) than in controls (P<0.05), and was higher in BEAS-2B cells 3 days post-detoxification (1.43±0.07) than in controls (P<0.05) . G0/G1 phase arrest was found in MRC-5 cells 24 hours post-treatment, and the apoptotic rates were significantly higher in MRC-5 cells 3 and 7 days post-detoxification than in controls [(11.53±1.53)%, (18.33±0.70)% vs. (3.53±0.93)%, P<0.05]. The overall apoptotic rates 24 hours post-treatment and 3 days post-detoxification [(2.80±0.17)%, (3.33±0.57)% vs. (1.53±0.61)%, P<0.05], proportion of ATM gene activation 3 days post-detoxification [(3.37±0.67%) vs. (1.18±0.22)%, P<0.05], proportion of double-strand DNA breaks 3 days post-detoxification [(4.45±0.85)% vs. (0.97±0.21)%, P<0.05] and percentage of the H2A.X variant histone phosphorylation 3 days post-detoxification [(1.68±0.56)% vs. (0.29±0.06)%, P<0.05] in BEAS-2B cells were higher than in controls. @*Conclusions@#Hexavalent chromium-induced rDNA copy number variation affects DNA damage response in different cell lines. A stronger DNA damage response is found in BEAS-2B cells with a low rDNA copy number, and a relative stable response is observed in MRC-5 cells with a high rDNA copy number.
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OBJECTIVES: This study aims to examine the association between occupational factors and semen quality in semen donors in eastern China. METHODS: We recruited 12 301 semen donors from 2006 to 2020 as the studying population. A self-designed questionnaire was applied for collecting lifestyle and work style information. Semen samples were analysed according to WHO guidelines. A crude and adjusted linear regression model was used to analyse the association between occupational factors and semen quality. RESULTS: College students accounted for 36.2% of all semen donors. The majority (81.3%) of semen donors were between 18 year and 30 years. Soldiers or the police had the highest semen volume (the median value=3.8 mL), however, they had the lowest sperm concentration (53.6×106/ml) and sperm motility (45.5%). Workers in finance or insurance had an elevated risk of low semen volume, sperm concentration and total sperm count (OR=1.43, 1.57 and 1.98, respectively). Unemployed men had a high risk of low sperm concentration and low total sperm count (OR=1.84 and 1.58, respectively). Working in the information technology industry had a deleterious effect on the progressive motility of sperm (OR=1.27, 95% CI 1.03 to 1.57). CONCLUSION: Our study indicated that sedentary work style and intensive sports in certain professions might be associated with decreased semen quality. We reported evidence of becoming unemployed on the damage to semen quality. Hence, we advocate a healthy work style to improve semen quality in eastern China.
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Análisis de Semen , Motilidad Espermática , China , Estudios Transversales , Humanos , Masculino , Ocupaciones , Semen , Recuento de Espermatozoides , Espermatozoides , Donantes de TejidosRESUMEN
Female workers in the asbestos processing industry of Eastern China are at high risk of developing multiple types of cancer, and more data are urgently needed to better understand and address this issue. Death certificate data were selected from an asbestos processing city in China from 2005 to 2006. Information was investigated using the relatives of those individuals who had died as sources of information. Individuals were classified into one of three asbestos exposure levels. Standardized mortality ratio and 95% confidence interval were calculated. A total of 2,964 individual deaths were identified from 2005 to 2006; of these, 21.4% were occupationally exposed to asbestos. The main cause of death was circulatory system diseases (21.2%). The proportion of individuals with respiratory system diseases increased by age among each exposure subgroup (P trend < 0.01). Among females, a significant trend was observed between increased asbestos exposure and mortality due to respiratory system diseases and lung cancer. Our study indicated that asbestos exposure was associated with excess mortality from lung cancer and respiratory diseases, particularly among female workers in an asbestos processing area in Eastern China.
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Linarin (acacetin-7-O-rutinoside), isorhoifolin (apigenin-7-O-rutinoside), and diosmin (diosmetin-7-O-rutinoside) are chemically and structurally similar flavone rutinoside (FR) compounds found in Chrysanthemum L. (Anthemideae, Asteraceae) plants. However, their biosynthetic pathways remain largely unknown. In this study, we cloned and compared FRs and genes encoding rhamnosyltransferases (RhaTs) among eight accessions of Chrysanthemum polyploids. We also biochemically characterized RhaTs of Chrysanthemum plants and Citrus (Citrus sinensis and Citrus maxima). RhaTs from these two genera are substrate-promiscuous enzymes catalyzing the rhamnosylation of flavones, flavanones, and flavonols. Substrate specificity analysis revealed that Chrysanthemum 1,6RhaTs preferred flavone glucosides (e.g. acacetin-7-O-glucoside), whereas Cs1,6RhaT preferred flavanone glucosides. The nonsynonymous substitutions of RhaTs found in some cytotypes of diploids resulted in the loss of catalytic function. Phylogenetic analysis and specialized pathways responsible for the biosynthesis of major flavonoids in Chrysanthemum and Citrus revealed that rhamnosylation activity might share a common evolutionary origin. Overexpression of RhaT in hairy roots resulted in 13-, 2-, and 5-fold increases in linarin, isorhoifolin, and diosmin contents, respectively, indicating that RhaT is mainly involved in the biosynthesis of linarin. Our findings not only suggest that the substrate promiscuity of RhaTs contributes to the diversity of FRs in Chrysanthemum species but also shed light on the evolution of flavone and flavanone rutinosides in distant taxa.
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Chrysanthemum , Citrus , Diosmina , Flavonas , Chrysanthemum/genética , Chrysanthemum/química , Filogenia , Flavonoides , Flavonas/química , Glucósidos/químicaRESUMEN
To evaluate the body burdens of heavy metals and explore the impact of environmental metal exposure on ribosomal DNA (rDNA) or mitochondrial DNA (mtDNA) copy number (CN) variation in school-age children living near a municipal waste incinerator (MWI), we conducted a follow-up study in 2019. A total of 146 sixth-grade children from a primary school located 1.2 km away from the MWI were recruited for our study. Metals, including vanadium (V), chromium (Cr), manganese (Mn), cobalt (Co), nickel (Ni), copper (Cu), zinc (Zn), arsenic (As), selenium (Se), cadmium (Cd), stannum (Sn), stibium (Sb), thallium (Tl), and lead (Pb), were determined by an inductively coupled plasma mass spectrometer method. Real-time qPCR was used to measure the rDNA and mtDNA CN. The blood metal levels followed this order: Zn > Cu > Se > Pb > Mn > Sb > As > Ni > Cd > Co > Cr > Sn > V > Tl. Blood Cr level was significantly correlated with 18 S, 2.5 S, and 45 S CN (ß = -0.25, -0.22, -0.26, p < 0.05); Ni was correlated with 5 S (ß = -0.36, p < 0.01); Cu was correlated with 28 S, 18 S, and 5.8 S (ß = -0.24, -0.24, -0.23, p < 0.05); while Zn was correlated with 18 S, 5.8 S, and 45 S (ß = -0.28, -0.32, -0.26, p < 0.05). In conclusion, school-age children living near the MWI had lower blood metal levels compared to children recruited in 2013, while rDNA CN loss was found to be correlated to several heavy metals in these children.
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Arsénico , Metales Pesados , Selenio , Cadmio/análisis , Niño , Cromo/análisis , Cobalto , Cobre , Variaciones en el Número de Copia de ADN , ADN Mitocondrial , ADN Ribosómico , Estudios de Seguimiento , Humanos , Plomo , Manganeso/análisis , Níquel/análisis , Talio , Estaño , Vanadio , ZincRESUMEN
Study Objectives: The purpose of this study was to determine the effects of daytime transcranial direct current stimulation (tDCS) on sleep electroencephalogram (EEG) in patients with depression. Methods: The study was a double-blinded, randomized, controlled clinical trial. A total of 37 patients diagnosed with a major depression were recruited; 19 patients (13 females and 6 males mean age 44.79 ± 15.25 years) received tDCS active stimulation and 18 patients (9 females and 9 males; mean age 43.61 ± 11.89 years) received sham stimulation. Ten sessions of daytime tDCS were administered with the anode over F3 and the cathode over F4. Each session delivered a 2 mA current for 30 min per 10 working days. Hamilton-24 and Montgomery scales were used to assess the severity of depression, and polysomnography (PSG) was used to assess sleep structure and EEG complexity. Eight intrinsic mode functions (IMFs) were computed from each EEG signal in a channel. The sample entropy of the cumulative sum of the IMFs were computed to acquire high-dimensional multi-scale complexity information of EEG signals. Results: The complexity of Rapid Eye Movement (REM) EEG signals significantly decreased intrinsic multi-scale entropy (iMSE) (1.732 ± 0.057 vs. 1.605 ± 0.046, P = 0.0004 in the case of the C4 channel, IMF 1:4 and scale 7) after tDCS active stimulation. The complexity of the REM EEG signals significantly increased iMSE (1.464 ± 0.101 vs. 1.611 ± 0.085, P = 0.001 for C4 channel, IMF 1:4 and scale 7) after tDCS sham stimulation. There was no significant difference in the Hamilton-24 (P = 0.988), Montgomery scale score (P = 0.726), and sleep structure (N1% P = 0.383; N2% P = 0.716; N3% P = 0.772) between the two groups after treatment. Conclusion: Daytime tDCS changed the complexity of sleep in the REM stage, and presented as decreased intrinsic multi-scale entropy, while no changes in sleep structure occurred. This finding indicated that daytime tDCS may be an effective method to improve sleep quality in depressed patients. Trial registration This trial has been registered at the ClinicalTrials.gov (protocol ID: TCHIRB-10409114, in progress).
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Patchouli (Pogostemon cablin (Blanco) Benth.), a member of the Lamiaceae family, is an important aromatic plant that has been widely used in medicine and perfumery. Here, we report a 1.94 Gb chromosome-scale assembly of the patchouli genome (contig N50 = 7.97 Mb). The gene annotation reveals that tandem duplication of sesquiterpene biosynthetic genes may be a major contributor to the biosynthesis of patchouli bioactivity components. We further phase the genome into two distinct subgenomes (A and B), and identify a chromosome substitution event that have occurred between them. Further investigations show that a burst of universal LTR-RTs in the A subgenome lead to the divergence between two subgenomes. However, no significant subgenome dominance is detected. Finally, we track the evolutionary scenario of patchouli including whole genome tetraploidization, subgenome divergency, hybridization, and chromosome substitution, which are the key forces to determine the complexity of patchouli genome. Our work sheds light on the evolutionary history of patchouli and offers unprecedented genomic resources for fundamental patchouli research and elite germplasm development.
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Lamiaceae , Pogostemon , Cromosomas , Haplotipos , Lamiaceae/genética , Pogostemon/genética , TetraploidíaRESUMEN
MAIN CONCLUSION: AaZFP1, a C2H2-type transcription factor, was found to bind the AGT-N1-10-AGT box of AaIPPI1pro and activate the expression of AaIPPI1 involved in artemisinin biosynthesis. Artemisinin, an endoperoxide sesquiterpene lactone, is a widely used antimalarial drug isolated from Artemisia annua L. Isopentenyl pyrophosphate isomerase (AaIPPI1) catalyzes the interconversion of isopentenyl diphosphate and dimethylallyl diphosphate and is the key gene involved in the biosynthesis of artemisinin. However, the AaIPPI1 gene regulation network remains largely unknown. Here, we isolated the AaIPPI1 promoter (AaIPPI1pro) and predicted that it contains cis-elements involved in stress responses, including the TGACG motif (a methyl jasmonate-responsive element), GARE motif (a gibberellin-responsive element), ABRE (an abscisic acid-responsive element), TC-rich repeats (a stress-responsive element), and the AGT-N1-10-AGT box, which is the binding site of Cys/His2 zinc finger protein (C2H2 ZFP). The C2H2 ZFP gene AaZFP1 was discovered by screening a cDNA library using AaIPPI1pro as bait in yeast. AaZFP1 contains two conserved C2H2 regions, a nuclear localization domain (B box), a Leu-rich domain (L box), and a conserved DLN sequence (DLN box) close to its C terminus. A subcellular localization assay indicated that AaZFP1 protein is localized in the nucleus and cytoplasm. An electrophoretic mobility shift assay demonstrated that AaZFP1 binds to the AGT-N1-10-AGT box of AaIPPI1pro. A dual-luciferase assay indicated that AaZFP1 enhanced the promoter activity of AaIPPI1 in vivo. Transient overexpression of AaZFP1 in A. annua increased the expression of AaIPPI1 and the content of artemisinin. Our data demonstrated that AaZFP1 functions as a transcriptional activator that regulates the expression of AaIPPI1 by directly binding to its promoter. The present study provides insights into the transcriptional regulation of genes involved in artemisinin biosynthesis in A. annua.
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Artemisia annua , Artemisininas , Dedos de Zinc CYS2-HIS2 , Ácido Abscísico/metabolismo , Artemisia annua/genética , Artemisia annua/metabolismo , Artemisininas/metabolismo , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismoRESUMEN
Objective @#To examine the effect of asbestos exposure on oxidative stress, so as to provide insights into the elucidation of pathogenesis and management of asbestos-related diseases. @*Methods @#Totally 245 subjects were recruited from an asbestos manufacturing area in Zhejiang Province, and their gender, age and history of asbestos exposure were collected through a questionnaire survey. The serum levels of 8-hydroxy-2'deoxyguanosine ( 8-OHdG ), glutathione ( GSH ), malondialdehyde ( MDA ), superoxide dismutase ( SOD ) and total antioxidative capacity ( TAOC ) were measured using an enzyme-linked immunosorbent assay ( ELISA ), and the levels of catalase ( CAT ), peroxiredoxin 2 ( PRX2 ), SOD1, SOD2 and thioredoxin-1 ( TRX1 ) were detected in peripheral white blood cells ( WBCs ) using a liquid-chip assay. Multivariable linear regression analysis was performed to identify the association between asbestos exposure and oxidative stress parameters. @*Results @#There were 50 subjects without a history of asbestos exposure (unexposed group), 102 subjects with asbestos exposure for less than 10 years ( AE<10-year group ) and 93 subjects with asbestos exposure for 10 years and more ( AE≥10-year group ). No significant differences were found among the three groups in terms of age, gender, proportion of smokers or proportion of alcohol consumers ( P>0.05 ). Significantly higher 8-OHdG and MDA in serum, and higher PRX2 in peripheral WBCs were detected in the AE≥10-year group than in the unexposed group ( P<0.05 ); lower GSH and TAOC in serum, and lower CAT in peripheral WBCs were detected in the AE≥10-year group than in the unexposed group ( P<0.05 ); higher 8-OHdG and MDA in serum, and higher PRX2 in peripheral WBCs were detected in the AE≥10-year group than in the AE<10-year group ( P<0.05 ). Multivariable linear regression analysis showed that asbestos exposure significantly correlated with 8-OHdG, MDA and TAOC in serum, and CAT and PRX2 in peripheral WBCs ( P<0.05 ). @*Conclusion @#Asbestos exposure may induce the oxidative stress damage, suggesting that oxidative stress may be involved in asbestos-related diseases.
RESUMEN
Objective @#To investigate the status of occupational stress and analyze its influencing factors among frontline employees working in a chemical fiber manufacturing enterprise, so as to provide insights into the development of occupational stress interventions. @*Methods @#The frontline employees working in a chemical fiber manufacturing enterprise were selected as the study subjects using a cluster sampling method in October 2018. The status of occupational stress was investigated using the Chinese version of the effort-reward imbalance ( ERI ) questionnaire. The influencing factors for occupational stress were identified using a multivariable logistic regression model. @*Results @#A total of 1 780 questionnaires were sent out, and 1 115 valid ones ( 62.64% ) were recovered. Among the 1 115 respondents, there were 427 men ( 38.30% ) and 688 women ( 61.70% ), and 71.22% were at ages of 21 to 39 years. There were 561 respondents with < 1 year of service ( 50.31% ), and the longest length of service was 11 years. In addition, there were 1 069 respondents ( 95.87% ) exposed to high noise, and 346 respondents ( 31.03% ) were diagnosed at a high occupational-stress state and 769 ( 68.97% ) at a low state. Multivariable logistic regression analysis identified 5 years or longer of service ( OR=1.540, 95%CI: 1.057-2.245 ) and exposure to high noise ( OR=1.917, 95%CI: 1.004-3.659 ) as risk factors for occupational stress among frontline employees in the chemical fiber manufacturing enterprise. @*Conclusions @#There are 31.03% of frontline employees at a high occupational-stress state in the chemical fiber manufacturing enterprise, and a high occupational-stress state is associated with exposure to high noise and 5 years or longer of service.
RESUMEN
Objective @#To analyze the survival of patients with malignant mesothelioma, so as to provide insights into the management of malignant mesothelioma.@*Methods @#Totally 36 patients with malignant mesothelioma admitted to Cixi Third People’s Hospital from October 2012 to January 2021 were enrolled, and the demographic features, exposure to asbestos, and diagnosis and treatment were retrospectively reviewed. The survival rate and median survival time were calculated with the life-table method, and the factors affecting the survival rate of malignant mesothelioma were identified using the Kaplan-Meier estimate and log-rank test.@*Results @#The 36 patients with malignant mesothelioma included 6 men ( 16.67% ) and 30 women ( 83.33% ), and had a median age of 61 ( interquartile range, 14 ) years. There were 30 cases with pleural malignant mesothelioma ( 83.33% ) and 6 cases with peritoneal malignant mesothelioma ( 16.67% ), 32 cases ( 88.89% ) with a history of occupational exposure to asbestos, and 26 cases ( 72.22% ) receiving palliative treatment. The 1-, 2- and 3-year cumulative survival rates were 30%, 15% and 3%, respectively, and the median survival time was 0.71 years. In addition, there were no significant differences in the survival period among patients with malignant mesothelioma in terms of gender, age, route of asbestos exposure, duration of asbestos exposure, pathogenic site and treatment regimens ( P>0.05 ).@*Conclusion @#The 36 patients with malignant mesothelioma had a median survival period of 0.71 years, and no association was found between the survival period and asbestos exposure or pathogenic site.