MYC and NCAPG2 as molecular targets of colorectal cancer and gastric cancer in nursing.

Colorectal cancer is a common malignant tumor in intestinal tract, the early symptoms are not obvious. Gastric cancer is a malignant tumor originating from the gastric mucosal epithelium. However, the role of MYC and non-SMC condensin II complex subunit G2 (NCAPG2) in colorectal cancer and gastric cancer remains unclear. The colorectal cancer datasets GSE49355 and gastric cancer datasets GSE19826 were downloaded from gene expression omnibus database. Differentially expressed genes (DEGs) were screened and weighted gene co-expression network analysis (WGCNA) was performed. Functional enrichment analysis, gene set enrichment analysis (GSEA) and immune infiltration analysis was performed. Construction and analysis of protein-protein interactions (PPI) network. Survival analysis and comparative toxicogenomics database (CTD) were performed. A heat map of gene expression was drawn. A total of 751 DEGs were obtained. According to the gene ontology (GO) analysis, in Biological process (BP) analysis, they are mainly enriched in cell differentiation, cartilage development, and skeletal development. In cellular component (CC) analysis, they are mainly enriched in the cytoskeleton of muscle cells and actin filaments. In molecular function (MF) analysis, they are mainly concentrated in Rho GTPase binding, DNA binding, and fibronectin binding. In Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis, they are mainly enriched in the MAPK signaling pathway, apoptosis, and cancer pathways. The soft threshold power for WGCNA analysis was set to 9, resulting in the generation of 40 modules. Ultimately, 2 core genes (MYC and NCAPG2) were identified. The heatmap of core gene expression showed high expression of MYC and NCAPG2 in colorectal cancer tissue samples and low expression in normal tissue samples, while they were core molecules in gastric cancer. Survival analysis indicated that MYC and NCAPG2 were risk factors, showing an upregulation trend with increasing risk scores. CTD analysis revealed associations of MYC and NCAPG2 with colorectal cancer, gastric cancer, inflammation, and immune system diseases. MYC and NCAPG2 are highly expressed in colorectal cancer. The higher the expression of MYC and NCAPG2, the worse the prognosis. MYC and NCAPG2 are core molecules in gastric cancer.

Application of Magnetic Resonance T1rho and T2 Mapping in Evaluating Cartilage Injury in Middle-aged and Elderly Patients with Knee Osteoarthritis.

Objective: To investigate magnetic resonance longitudinal relaxation time quantitative imaging (T1rho) and transverse relaxation time quantitative imaging (T2 mapping) techniques in evaluating cartilage damage in middle-aged and elderly patients with knee osteoarthritis (OA). Methods: To carry out this investigation, the researchers enrolled 65 OA patients subjects for the study. These patients were divided into 2 groups based on the severity of their OA. Thirty healthy individuals were included as the control group. All study participants underwent magnetic resonance T1rho and T2 mapping scans. OA patient scores and values from the Western Ontario and McMaster University Osteoarthritis Index (WOMAC), T2, and a T1rho MRI measurement indicating potential early indication of bone and joint diseases from each cartilage area were compared among the OA patients as well as the control group. Pearson correlation analysis was used to examine the relationships between T2 and T1rho values and WOMAC scores. Results: The WOMAC scores in the mild OA group were lower than the severe OA group (P < .05). There were no significant differences in T2 and T1rho values of lateral tibial cartilage among the 3 groups (P > .05). On the other hand, the T2 and T1rho values of medial femoral, lateral femoral, and medial tibial cartilage areas increased progressively in the control, mild OA, and severe OA groups (P < .05). A Pearson analysis found a positive correlation between the T2 values of medial, lateral, and medial tibial cartilages and the WOMAC scores. Similarly, the T1rho values of these cartilage areas were also positively correlated with the WOMAC scores. Conclusion: Magnetic resonance T1rho and T2 mapping offer good evaluation value for assessing cartilage injury in middle-aged and elderly patients with knee OA. The values obtained from T1rho and T2 mapping in various areas of the cartilage show a positive correlation with WOMAC scores.

Spinosin inhibits activated hepatic stellate cell to attenuate liver fibrosis by targeting Nur77/ASK1/p38 MAPK signaling pathway.

AIM: Liver fibrosis remains a great challenge in the world. Spinosin (SPI), a natural flavonoid-C-glycoside, possesses various pharmacological activities including anti-inflammatory and anti-myocardial fibrosis effects. In this study, we investigate whether SPI can be a potential lead for the treatment of liver fibrosis and explore whether the orphan nuclear receptor Nur77, a negative regulator of liver fibrosis development, plays a critical role in SPI's action. METHODS: A dual luciferase reporter system of α-SMA was established to evaluate the effect of SPI on hepatic stellate cell (HSC) activation in LX2 and HSC-T6 cells. A mouse model of CCl4-induced liver fibrosis was used to test the efficacy of SPI against liver fibrosis. The expression levels of Nur77, inflammatory cytokines and collagen were determined by Western blotting and qPCR. Potential kinase pathways involved were also analyzed. The affinity of Nur77 with SPI was documented by fluorescence titration. RESULTS: SPI can strongly suppress TGF-ß1-mediated activation of both LX2 and HSC-T6 cells in a dose-dependent manner. SPI increases the expression of Nur77 and reduces TGF-ß1-mediated phosphorylation levels of ASK1 and p38 MAPK, which can be reversed by knocking out of Nur77. SPI strongly inhibits collagen deposition (COLA1) and reduces inflammatory cytokines (IL-6 and IL-1ß), which is followed by improved liver function in the CCl4-induced mouse model. SPI can directly bind to R515 and R563 in the Nur77-LBD pocket with a Kd of 2.14 µM. CONCLUSION: Spinosin is the major pharmacological active component of Ziziphus jujuba Mill. var. spinosa which has been frequently prescribed in traditional Chinese medicine. We demonstrate here for the first time that spinosin is a new therapeutic lead for treatment of liver fibrosis by targeting Nur77 and blocking the ASK1/p38 MAPK signaling pathway.

MIR503HG Overexpression Inhibits the Malignant Behaviors of Osteosarcoma Cells by Sponging miR-103a-3p.

Osteosarcoma (OS) is the most representative primary bone tumour in children and teenagers. This study explored the regulatory effects of long noncoding RNA MIR503HG (MIR503HG) on the biological functions of OS cells, and further investigated the potential mechanism of MIR503HG function exertion by analyzing the microRNA-103a-3p (miR-103a-3p) in OS cells and tissues. The expression of MIR503HG was examined using reverse transcription-quantitative PCR. OS cell proliferation was assessed by CCK-8 assay. Transwell assay was used to evaluate the migration and invasion of OS cells. The interaction between MIR503HG and miR-103a-3p was detected using the Dual-luciferase reporter assay. Forty-six paired OS tissues were collected, and the expression and correlation of MIR503HG and miR-103a-3p were evaluated. The expression of MIR503HG were significantly decreased in both OS cells and tissues. Over-expression of MIR503HG inhibited OS cell proliferation, migration and invasion. miR-103a-3p was directly targeted by MIR503HG in OS cells, and mediated the inhibitory effects of MIR503HG on OS cell malignant behaviors. miR-103a-3p expression was upregulated in OS tissues, which was negatively correlated with MIR503HG expression levels. The expression of MIR503HG was associated with OS patients' tumor size, differentiation, distant metastasis and clinical stage. Decreased MIR503HG in OS tissues and cell lines served as a tumor suppressor by inhibiting OS cell malignant behaviors through sponging miR-103a-3p. The findings of this study may provide evidence for the development of novel therapeutic targets of OS.

Effects of ambient particulate exposure on blood lipid levels in hypertension inpatients.

Background: With modernization development, multiple studies of atmospheric particulate matter exposure conducted in China have confirmed adverse cardiovascular health effects. However, there are few studies on the effect of particulate matter on blood lipid levels in patients with cardiovascular disease, especially in southern China. The purpose of this study was to investigate the association between short- and long-term exposure to ambient particulate matter and the levels of blood lipid markers in hypertension inpatients in Ganzhou, China. Methods: Data on admission lipid index testing for hypertension inpatients which were divided into those with and without arteriosclerosis disease were extracted from the hospital's big data center from January 1, 2016 to December 31, 2020, and air pollution and meteorology data were acquired from the China urban air quality real time release platform from January 1, 2015 to December 31, 2020 and climatic data center from January 1, 2016 to December 31, 2020, with data integrated according to patient admission dates. A semi-parametric generalized additive model (GAM) was established to calculate the association between ambient particulate matter and blood lipid markers in hypertension inpatients with different exposure time in 1 year. Results: Long-term exposure to particulate matter was associated with increased Lp(a) in three kinds of people, and with increased TC and decreased HDL-C in total hypertension and hypertension with arteriosclerosis. But particulate matter was associated with increased HDL-C for hypertension inpatients without arteriosclerosis, at the time of exposure in the present study. It is speculated that hypertension inpatients without arteriosclerosis has better statement than hypertension inpatients with arteriosclerosis on human lipid metabolism. Conclusion: Long-term exposure to ambient particulate matter is associated with adverse lipid profile changes in hypertension inpatients, especially those with arteriosclerosis. Ambient particulate matter may increase the risk of arteriosclerotic events in hypertensive patients.

Stable Mo/1T-MoS2 Monolith Catalyst with a Metallic Interface for Large Current Water Splitting.

To achieve global carbon neutrality, the realization of highly active and stable catalysts is critical for water splitting to produce green hydrogen (H2). MoS2 is considered to be the most promising non-precious metal catalyst for H2 evolution because of its excellent properties. Herein, we report a metal-phase MoS2 (1T-MoS2) synthesized using a simple hydrothermal method. Using a similar procedure, we synthesize a monolithic catalyst (MC) in which 1T-MoS2 is vertically bonded to a metal molybdenum plate via strong covalent bonds. These properties endow the MC with an extremely low-resistance interface and mechanical robustness, equipping it with outstanding durability and fast charge transfer. Results show that the MC can achieve stable water splitting at 350 mA cm-2 current density with a low 400 mV overpotential. The MC exhibits negligible performance decay after 60 h of operation at a large current density of 350 mA cm-2. This study provides a novel possible MC with robust and metallic interfaces to achieve technically high current water splitting to produce green H2.

Volatile Profiling and Transcriptome Sequencing Provide Insights into the Biosynthesis of α-Pinene and ß-Pinene in Liquidambar formosana Hance Leaves.

Liquidambar formosana Hance is a pinene-rich deciduous plant species in the Altingiaceae family that is used as a medicinal plant in China. However, the regulatory mechanisms underlying α-pinene and ß-pinene biosynthesis in L. formosana leaves remain unknown. Here, a joint analysis of the volatile compounds and transcriptomes of L. formosana leaves was performed to comprehensively explore the terpene synthase (TPS) that may participate in α-pinene and ß-pinene biosynthesis. Headspace solid-phase microextraction (HS-SPME) and gas chromatography-mass spectrometry (GC-MS) jointly detected volatile L. formosana leaves. Trees with high and low levels of both α-pinene and ß-pinene were defined as the H group and L group, respectively. RNA sequencing data revealed that DXR (1-deoxy-D-xylulose-5-phosphate reductoisomerase), HDS [(E)-4-hydroxy-3-methylbut-2-eny-l-diphosphate synthase], and TPS may be the major regulators of monoterpenoid biosynthesis. We identified three TPSs (LfTPS1, LfTPS2, and LfTPS3), which are highly homologous to α-pinene and ß-pinene synthases of other species in phylogenetic analysis. Four TPS genes (LfTPS1, LfTPS2, LfTPS4, LfTPS5) may be critically involved in the biosynthesis and regulation of α-pinene and ß-pinene in L. formosana. Bioinformatic and transcriptomic results were verified using quantitative real-time PCR. We identified LfTPS1, LfTPS2 as candidate genes for α-pinene and ß-pinene biosynthesis that significantly improve the yield of beneficial terpenoids.

MnO2-based materials for supercapacitor electrodes: challenges, strategies and prospects.

Manganese dioxide (MnO2) has always been the ideal electrode material for supercapacitors due to its non-toxic nature and high theoretical capacity (1370 F g-1). Over the past few years, significant progress has been made in the development of high performance MnO2-based electrode materials. This review summarizes recent research progress in experimental, simulation and theoretical studies for the modification of MnO2-based electrode materials from different perspectives of morphology engineering, defect engineering and heterojunction engineering. Several main approaches to achieve enhanced electrochemical performance are summarized, respectively increasing the effective active site, intrinsic conductivity and structural stability. On this basis, the future problems and research directions of electrode materials are further envisaged, which provide theoretical guidance for the adequate design and synthesis of MnO2-based electrode materials for use in supercapacitors.

A colorimetric sensing platform for the determination of H2O2 using 2D-1D MoS2-CNT nanozymes.

A novel colorimetric platform based on nano-composites of two-dimensional (2D) molybdenum disulfide nanosheets (MoS2 NSs) and one-dimensional (1D) carbon nanotubes (CNTs), called 2D-1D MoS2-CNT nanozyme, was fabricated for the selective and sensitive determination of hydrogen peroxide (H2O2) in soda water. The MoS2-CNT nanozyme was synthesized through a one-step solvothermal reduction method. The introduced CNTs could effectively prevent the stacking of MoS2 nanosheets (NSs) and not only expanded the interlayer distance of MoS2 NSs from 0.620 nm to 0.710 nm but also improved their specific surface. Under acidic conditions, the as-prepared 2D-1D MoS2-CNT nanozymes could oxidize the colorless 3,3',5,5'-tetramethylbenzidine (TMB) to blue-oxidized TMB (oxTMB) in the presence of H2O2, resulting in enhanced peroxidase-like (POD-like) activity. The kinetic study showed that MoS2-CNT nanozyme had stronger catalytic activity than natural horseradish peroxidase (HRP). The linear range for H2O2 colorimetric determination was 5.00-500 µmol L-1 with a limit of detection (LOD) of 1.40 µmol L-1. Furthermore, the established determination method was applied to actual samples and the recoveries of H2O2 spiked in soda water were in the range of 92.3-107%, showing feasibility for the analysis of food.

Strong Metal-Support Interactions of Ni-CeO2 Effectively Improve the Performance of a Molten Hydroxide Direct Carbon Fuel Cell.

A strong metal-support interaction (SMSI) type catalyst has been synthesized and applied to a molten hydroxide direct carbon fuel cell (MHDCFC) to enhance the reaction activity of the anode carbon fuel through the interaction between the metal Ni and the support CeO2. Two catalysts have been prepared by a direct precipitation method (denoted NiO@CeO2) and a hydrothermal method (denoted NiO-CeO2), which are reduced by H2 to obtain Ni@CeO2 and Ni-CeO2, respectively. X-ray photoelectron spectroscopy (XPS), Raman, and temperature-programmed hydrogen reduction (H2-TPR) analysis results show that there are obvious oxygen vacancies and a Ni-O-Ce interface structure in NiO-CeO2 and Ni-CeO2, which is induced by the interaction between Ni and CeO2. The calculation results of current density and power density show that the performance of the MHDCFC is significantly improved in the presence of Ni-CeO2. The function fitting curves of the logarithm of the reaction rate constant (ln k) and the reciprocal of the temperature (1/T) show that the slope of the curve is decreased significantly after the addition of Ni-CeO2. In combination with density functional theory (DFT), the anode carbon reaction path is simulated in the MHDCFC, and the calculation results show that the reaction energy for the anodic carbon to generate carbon dioxide is decreased by 1.03 eV in the presence of Ni-CeO2.

Blockage of TIM-3 relieves lupus nephritis by expanding Treg cells and promoting their suppressive capacity in MRL/lpr mice.

T Cell Immunoglobulin and Mucin Containing Protein-3 (TIM-3) is an important immune checkpoint protein that is expressed in Tregs and affects their function. However, the expression and role of TIM-3 in modulating regulatory T cells (Tregs) in lupus nephritis (LN) are still unknown. In this study, we found that the percentage of TIM-3+ cells among spleen lymphocytes, CD4+ T cells and Tregs was higher in MRL/lpr mice than in MpJ mice. TIM-3high CD4+ T cells and TIM-3high Tregs were mainly responsible for the increase. The percentage of Tregs in TIM-3high CD4+ T cells was lower than that in TIM-3low CD4+ T cells, and the expression of CTLA-4 and IL-10 was lower in TIM-3high Tregs than in the TIM-3low Tregs in MRL/lpr mice. Blockade of TIM-3 in vivo significantly increased the Treg population and the expression of CTLA-4 and IL-10 in Tregs, thus relieving the LN symptoms and pathology in MRL/lpr mice. Additionally, bioinformatics analysis indicated that TIM-3 regulates Treg cells in LN mainly through cytokine-cytokine receptor interactions, the PI3K-Akt signaling pathway, the T cell receptor signaling pathway, Th17 cell differentiation and the FoxO signaling pathway. Together, our study has demonstrated that TIM-3 regulates Tregs in LN and that overexpression of TIM-3 in CD4+ T cells and Tregs leads to Treg quantity and quality deficiency in MRL/lpr mice. Blockade of TIM-3 protects against LN by expanding Tregs and enhancing their suppressive capacity. Finally, TIM-3 might be a potential therapeutic target for the treatment of LN.

Ambient air pollutants relate to hospital admissions for chronic obstructive pulmonary disease in Ganzhou, China.

OBJECTIVE: To evaluate the relationship between ambient air pollutants and chronic obstructive pulmonary disease in relatively low-polluted areas in China. METHODS: Atmospheric pollutants levels and meteorological data were obtained from January 2016 to December 2020. The medical database including daily hospital admissions for chronic obstructive pulmonary disease (ICD10: J44) was derived from the First Affiliated Hospital of Gannan Medical University. The generalized additive model was used to analyze the percentage change with 95% confidence interval in daily hospital admissions for chronic obstructive pulmonary disease associated with a 10 µg/m3 increase in atmospheric pollutants levels. RESULTS: In total, occurred 4,980 chronic obstructive pulmonary disease hospital admissions (not including emergency department visits) during 2016-2020. The mean concentrations of daily PM2.5, PM10, SO2, NO2, O3, and CO were 37.5 µg/m3, 60.1 µg/m3, 18.7 µg/m3, 23.5 µg/m3, 70.0 µg/m3, and 1.2 mg/m3 in Ganzhou. Each 10 µg/m3 increment of PM2.5, PM10, NO2, and O3 were significantly associated with 2.8% (95%CI: 1.0-4.7), 1.3% (95%CI: 0.3-2.4), 2.8% (95%CI: 0.4-5.4), and 1.5% (95%CI: 0.2-2.7) elevation in daily chronic obstructive pulmonary disease hospital admissions. The estimates of delayed effects of PM2.5, PM10, NO2, and O3 were observed at lag6, lag6, lag8, lag1, respectively. The health effects of particulate pollutants (PM2.5 and PM10) may be independent of other pollutants. The adverse effects of air pollutants were more evident in the warm season (May-Oct) than in the cold season (Nov-Apr). CONCLUSION: Our study demonstrated that elevated concentrations of atmospheric pollutant (PM2.5, PM10, NO2, and O3), especially particulate pollutants, can be associated with increased daily count of hospital admissions for chronic obstructive pulmonary disease , which may promote further understanding of the potential hazards of relatively low levels of air pollution on chronic obstructive pulmonary disease and other respiratory disorders.

A free-standing VN/MXene composite anode for high-performance Li-ion hybrid capacitors.

The Li-ion hybrid capacitor (LIHC) is considered as a promising candidate for electrochemical energy storage owing to the high energy and power density. However, the sluggish anodic reaction kinetics and high reaction voltage greatly hinder the overall performance of LIHCs. Herein, a free-standing VN/MXene composite anode with high specific capacity and low reaction voltage was prepared by a simple vacuum filtration method. The obtained VN/MXene composite anode shows a high discharge specific capacity of 501.7 mA h g-1 at 0.1 A g-1 and excellent rate capability (191.8 mA h g-1 at 5 A g-1), as well as much extended cycling stability (1500 cycles at 2 A g-1). When combined with an egg white-derived activated carbon (E-AC) cathode, the assembled LIHC delivers a high specific capacity of 59.1 F g-1 and a high energy density of 129.3 W h kg-1 with a power density of 449.7 W kg-1. Even at a high current density of 5 A g-1, the LIHC still maintains an exciting energy density of 42.81 W h kg-1 at 11 249 W kg-1. Meanwhile, the cycling life can be extended to 5000 cycles with a high capacity retention of 98% at 1 A g-1. We believe that this work opens up new possibilities for developing advanced free-standing MXene-based electrodes for Li-ion storage.

A Free-Standing α-MoO3/MXene Composite Anode for High-Performance Lithium Storage.

Replacing the commercial graphite anode in Li-ion batteries with pseudocapacitor materials is an effective way to obtain high-performance energy storage devices. α-MoO3 is an attractive pseudocapacitor electrode material due to its theoretical capacity of 1117 mAh g-1. Nevertheless, its low conductivity greatly limits its electrochemical performance. MXene is often used as a 2D conductive substrate and flexible framework for the development of a non-binder electrode because of its unparalleled electronic conductivity and excellent mechanical flexibility. Herein, a free-standing α-MoO3/MXene composite anode with a high specific capacity and an outstanding rate capability was prepared using a green and simple method. The resultant α-MoO3/MXene composite electrode combines the advantages of each of the two components and possesses improved Li+ diffusion kinetics. In particular, this α-MoO3/MXene free-standing electrode exhibited a high Li+ storage capacity (1008 mAh g-1 at 0.1 A g-1) and an outstanding rate capability (172 mAh g-1 at 10 A g-1), as well as a much extended cycling stability (500 cycles at 0.5 A g-1). Furthermore, a full cell was fabricated using commercial LiFePO4 as the cathode, which displayed a high Li+ storage capacity of 160 mAh g-1 with an outstanding rate performance (48 mAh g-1 at 1 A g-1). We believe that our research reveals new possibilities for the development of an advanced free-standing electrode from pseudocapacitive materials for high-performance Li-ion storage.

Type I collagen reduces lipid accumulation during adipogenesis of preadipocytes 3T3-L1 via the YAP-mTOR-autophagy axis.

The extracellular matrix (ECM) regulates cell behavior through signal transduction and provides a suitable place for cell survival. As one of the major components of the extracellular matrix, type I collagen is involved in regulating cell migration, proliferation and differentiation. We present a system in which 3T3-L1 preadipocyte cells are induced for adipogenic differentiation on type I collagen coated dishes. Our previous study has found that type I collagen inhibits adipogenic differentiation via YAP activation. Here we further reveal that type I collagen inactivates autophagy by up-regulating mTOR activity via the YAP pathway. Under collagen-coating conditions, co-localization of lysosomes with mTOR was increased and the level of downstream protein p-S6K was elevated, accompanied by a decrease in the level of autophagy. Autophagy is negatively correlated with adipogenesis under type I collagen coating. Through the YAP-autophagy axis, type I collagen improves glycolipid metabolism accompanied by increased mitochondrial content, enhanced glucose uptake, reduced release of free fatty acids (FFAs) and decreased intracellular lipid accumulation. Our findings provide insight into the strategy for dealing with obesity: Type I collagen or the drugs with inhibitory effects on autophagy or YAP, have a potential to accelerate the energy metabolism of adipose tissue, so as to better maintain the homeostasis of glucose and lipids in the body, which can be used for achieving weight loss.

Association Between Sulfur Dioxide and Daily Inpatient Visits With Respiratory Diseases in Ganzhou, China: A Time Series Study Based on Hospital Data.

Background: Sulfur dioxide (SO2) has been reported to be related to the mortality of respiratory diseases, but the relationship between SO2 and hospital inpatient visits with respiratory diseases and the potential impact of different seasons on this relationship is still unclear. Methods: The daily average concentrations of air pollutants, including SO2 and meteorological data in Ganzhou, China, from 2017 to 2019 were collected. The data on daily hospitalization for respiratory diseases from the biggest hospital in the city were extracted. The generalized additive models (GAM) and the distributed lag non-linear model (DLNM) were employed to evaluate the association between ambient SO2 and daily inpatient visits for respiratory diseases. Stratified analyses by gender, age, and season were performed to find their potential effects on this association. Results: There is a positive exposure-response relationship between SO2 concentration and relative risk of respiratory inpatient visits. Every 10 µg/m3 increase in SO2 was related to a 3.2% (95% CI: 0.6-6.7%) exaltation in daily respiratory inpatient visits at lag3. In addition, SO2 had a stronger association with respiratory inpatient visits in women, older adults (≥65 years), and warmer season (May-Oct) subgroups. The relationship between SO2 and inpatient visits for respiratory diseases was robust after adjusting for other air pollutants, including PM10, NO2, O3, and CO. Conclusion: This time-series study showed that there is a positive association between short-term SO2 exposure and daily respiratory inpatient visits. These results are important for local administrators to formulate environmental public health policies.

Anticancer activity of Germacrone terpenoid in human osteosarcoma cells is mediated via autophagy induction, cell cycle disruption, downregulating the cell cycle regulatory protein expressions and cell migration inhibition.

Germacrone a sesquiterpene is a potential pharmacological agent with important medicinal applications. It is a potential anticancer agent and has been reported for anticancer activity against hepatoma cells and breast cancer cells, additionally, it has also shown anti-inflammatory, antioxidant, and antifungal activity. Therefore, this study was designed to testify anticancer activity of germacrone terpenoid in human osteosarcoma cells along with studying its effects of autophagy induction, cell cycle disruption, downregulating the cell cycle regulatory protein expressions and cell migration inhibition. Cell proliferation rate was examined by MTT assay and phase contrast inverted microscopy was performed for morphological analysis. Further, flowcytometry was implemented to examine different cell cycle phases. Transwell assay was executed for the monitoring of cell migratory tendency of osteosarcoma cells. Finally, the levels of pro-autophagic and cell cycle allied proteins were checked by Western blot analysis. MTT assay results designated potential inhibition of osteosarcoma cell viability by germacrone drug in a dose and time-reliant manner. Further, phase contrast inverted microscopy depicted significant morphological changes in osteosarcoma cells after germacrone exposure, which were indicative of autophagic cell death. Next, transmission electron microscopy evaluated the formation of autophagic vesicles which are the trademark for autophagy. The autophagy allied protein expressions were observed through Western blotting indicating enhanced levels of pro-autophagic proteins (Becalin-1, LC3-I and -II). Hence, it may be depicted that the anti-proliferation effects of germacrone may be of autophagy inducing potential. Next, flowcytometric analysis revealed the cell cycle inhibitory effects of germacrone in osteosarcoma cells and the results indicated cell cycle arrest at S-phase. Cell cycle allied protein levels indicated declination in their expressions after germacrone exposure. Finally, transwell assay specified inhibitory effects on cell migration of osteosarcoma cells by germacrone in a dose-reliant manner. In conclusion, the results of the present investigation specified that germacrone drug is a potential anticancer agent against osteosarcoma cells. The anticancer effects were found to be mediated via autophagy induction, cell cycle disruption, downregulating the cell cycle regulatory protein expressions, and cell migration inhibition.

Genome-Wide Association Study of Salt Tolerance at the Seed Germination Stage in Flax (Linum usitatissimum L.).

Soil salinization seriously affects the growth and distribution of flax. However, there is little information about the salt tolerance of flax. In this study, the salt tolerance of 200 diverse flax accessions during the germination stage was evaluated, and then the Genome-wide Association Study (GWAS) was carried out based on the relative germination rate (RGR), relative shoot length (RSL) and relative root length (RRL), whereby quantitative trait loci (QTLs) related to salt tolerance were identified. The results showed that oil flax had a better salt tolerance than fiber flax. A total of 902 single nucleotide polymorphisms (SNPs) were identified on 15 chromosomes. These SNPs were integrated into 64 QTLs, explaining 14.48 to 29.38% (R2) of the phenotypic variation. In addition, 268 candidate genes were screened by combining previous transcriptome data and homologous gene annotation. Among them, Lus10033213 is a single-point SNP repeat mapping gene, which encodes a Glutathione S-transferase (GST). This study is the first to use GWAS to excavate genes related to salt tolerance during the germination stage of flax. The results of this study provide important information for studying the genetic mechanism of salt tolerance of flax, and also provide the possibility to improve the salt tolerance of flax.

Association between Particulate Matter Pollution Concentration and Hospital Admissions for Hypertension in Ganzhou, China.

Fine particulate matter (PM2.5) and respirable particulate matter (PM10) are two major air pollutants with toxic effects on the cardiovascular system. Hypertension, as a chronic noncommunicable cardiovascular disease, is also a risk factor for several diseases. We applied generalized linear models with a quasi-Poisson link to assess the effect of air pollution exposure on the number of daily admissions for patients with hypertension. In addition, we established a two-pollutant model to evaluate PM2.5 and PM10 hazard effect stability by adjusting the other gaseous pollutants. Results showed that during the study period, 24 h mean concentrations of ambient PM2.5 and PM10 at 38.17 and 59.84 µg/m3, respectively, and a total of 2,611 hypertension hospital admissions were recorded. Air pollution concentrations significantly affected the number of hospitalizations for hypertension approximately 2 months after exposure. For each 10 µg/m3 increase in PM2.5 and PM10 in single-pollutant models, the number of hospitalizations for hypertension increased by 7.92% (95% CI: 5.48% to 10.42%) and 4.46% (95% CI: 2.86% to 5.65%), respectively, at the lag day with the strongest effect. NO2, O3, CO, and SO2 had different significant effects on the number of hospitalizations over the same time period, and PM2.5 and PM10 still showed robust significant effects after adjustment of gas pollutants through a two-pollutant model. These findings may contribute to a better understanding of the health effects of ambient particulate matter.

Yttrium chloride-induced cytotoxicity and DNA damage response via ROS generation and inhibition of Nrf2/PPARγ pathways in H9c2 cardiomyocytes.

Increasing exploration of rare-earth elements (REEs) has resulted in a high REEs' exposure risk. Owing to their persistence and accumulation of REEs in the environment, their adverse effects have caused widespread concern. However, limited toxicological data are available for the adverse effects of yttrium (Y) and its underlying mechanisms of action. In the present study, H9c2 cardiomyocytes were used in vitro model to investigate the cardiotoxicity of yttrium chloride (YCl3). Results show that YCl3 treatment resulted in reactive oxygen species (ROS) overproduction, decrease in ∆Ψm, and DNA damage. Mechanistically, we detected expression levels of protein in response to cellular DNA damage and antioxidative defense. Results indicated that the phosphorylation of histone H2AX remarkably increased in a dose-dependent manner. At a high YCl3-exposure concentration (120 µM), specific DNA damage sensors ATM/ATR-Chk1/Chk2 were significantly decreased. The protein levels of key antioxidant genes Nrf2/PPARγ/HO-1 were also remarkably inhabited. Additionally, the antioxidant N-acetyl-L-cysteine (NAC) pretreatment promoted the activation of antioxidative defense Nrf2/PPARγ signaling pathways, and prevented the production of cellular ROS, thus protecting the DNA from cleavage. Altogether, our findings suggest that YCl3 can induce DNA damage through causing intracellular ROS overproduction and inhibition of antioxidative defense, leading to cytotoxicity in H9c2 cardiomyocytes.