ABSTRACT
The evolutionarily conserved target of rapamycin (TOR) kinase acts as a master regulator that coordinates cell proliferation and growth by integrating nutrient, energy, hormone and stress signals in all eukaryotes1,2. Research has focused mainly on TOR-regulated translation, but how TOR orchestrates the global transcriptional network remains unclear. Here we identify ethylene-insensitive protein 2 (EIN2), a central integrator3-5 that shuttles between the cytoplasm and the nucleus, as a direct substrate of TOR in Arabidopsis thaliana. Glucose-activated TOR kinase directly phosphorylates EIN2 to prevent its nuclear localization. Notably, the rapid global transcriptional reprogramming that is directed by glucose-TOR signalling is largely compromised in the ein2-5 mutant, and EIN2 negatively regulates the expression of a wide range of target genes of glucose-activated TOR that are involved in DNA replication, cell wall and lipid synthesis and various secondary metabolic pathways. Chemical, cellular and genetic analyses reveal that cell elongation and proliferation processes that are controlled by the glucose-TOR-EIN2 axis are decoupled from canonical ethylene-CTR1-EIN2 signalling, and mediated by different phosphorylation sites. Our findings reveal a molecular mechanism by which a central signalling hub is shared but differentially modulated by diverse signalling pathways using distinct phosphorylation codes that can be specified by upstream protein kinases.
Subject(s)
Arabidopsis Proteins/metabolism , Arabidopsis/growth & development , Arabidopsis/metabolism , Cell Nucleus/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Plant Development , Receptors, Cell Surface/metabolism , Signal Transduction , Arabidopsis/cytology , Arabidopsis/genetics , Catalytic Domain , DNA-Binding Proteins/metabolism , Ethylenes/metabolism , Glucose/metabolism , Intracellular Signaling Peptides and Proteins/metabolism , Meristem/metabolism , Phosphorylation , Plant Growth Regulators/metabolism , Protein Kinases/metabolism , Substrate Specificity , Transcription Factors/metabolism , TranscriptomeABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a lethal progressive disease with elusive molecular mechanisms and limited therapeutic options. Aberrant activation of fibroblasts is a central hallmark of lung fibrosis. Here, we report that Golgi membrane protein 1 (GOLM1, also known as GP73 or GOLPH2) was increased in the lungs of patients with pulmonary fibrosis and mice with bleomycin (BLM)-induced pulmonary fibrosis. Loss of GOLM1 inhibited proliferation, differentiation, and extracellular matrix deposition of fibroblasts, whereas overexpression of GOLM1 exerted the opposite effects. Similarly, worsening pulmonary fibrosis after BLM treatment was observed in GOLM1-knock-in mice, whereas BLM-treated Golm1-knockout mice exhibited alleviated pulmonary fibrosis and collagen deposition. Furthermore, we identified long noncoding RNA NEAT1 downstream of GOLM1 as a potential mediator of pulmonary fibrosis through increased GOLM1 expression. Depletion of NEAT1 inhibited fibroblast proliferation and extracellular matrix production and reversed the profibrotic effects of GOLM1 overexpression. Additionally, we identified KLF4 as a downstream mediator of GOLM1 signaling to NEAT1. Our findings suggest that GOLM1 plays a pivotal role in promoting pulmonary fibrosis through the GOLM1-KLF4-NEAT1 signaling axis. Targeting GOLM1 and its downstream pathways may represent a novel therapeutic strategy for treating pulmonary fibrosis.
Subject(s)
Idiopathic Pulmonary Fibrosis , Animals , Humans , Mice , Bleomycin , Extracellular Matrix , Fibroblasts , Idiopathic Pulmonary Fibrosis/chemically induced , Idiopathic Pulmonary Fibrosis/genetics , Membrane Proteins/genetics , Mice, Knockout , Up-RegulationABSTRACT
BACKGROUND & AIMS: Dysregulation of alternative splicing is implicated in many human diseases, and understanding the genetic variation underlying transcript splicing is essential to dissect the molecular mechanisms of cancers. We aimed to provide a comprehensive functional dissection of splicing quantitative trait loci (sQTLs) in cancer and focus on elucidating its distinct role in colorectal cancer (CRC) mechanisms. METHODS: We performed a comprehensive sQTL analysis to identify genetic variants that control messenger RNA splicing across 33 cancer types from The Cancer Genome Atlas and independently validated in our 154 CRC tissues. Then, large-scale, multicenter, multi-ethnic case-control studies (34,585 cases and 76,023 controls) were conducted to examine the association of these sQTLs with CRC risk. A series of biological experiments in vitro and in vivo were performed to investigate the potential mechanisms of the candidate sQTLs and target genes. RESULTS: The molecular characterization of sQTL revealed its distinct role in cancer susceptibility. Tumor-specific sQTL further showed better response to cancer development. In addition, functionally informed polygenic risk score highlighted the potentiality of sQTLs in the CRC prediction. Complemented by large-scale population studies, we identified that the risk allele (T) of a multi-ancestry-associated sQTL rs61746794 significantly increased the risk of CRC in Chinese (odds ratio, 1.20; 95% CI, 1.12-1.29; P = 8.82 × 10-7) and European (odds ratio, 1.11; 95% CI, 1.07-1.16; P = 1.13 × 10-7) populations. rs61746794-T facilitated PRMT7 exon 16 splicing mediated by the RNA-binding protein PRPF8, thus increasing the level of canonical PRMT7 isoform (PRMT7-V2). Overexpression of PRMT7-V2 significantly enhanced the growth of CRC cells and xenograft tumors compared with PRMT7-V1. Mechanistically, PRMT7-V2 functions as an epigenetic writer that catalyzes the arginine methylation of H4R3 and H3R2, subsequently regulating diverse biological processes, including YAP, AKT, and KRAS pathway. A selective PRMT7 inhibitor, SGC3027, exhibited antitumor effects on human CRC cells. CONCLUSIONS: Our study provides an informative sQTLs resource and insights into the regulatory mechanisms linking splicing variants to cancer risk and serving as biomarkers and therapeutic targets.
ABSTRACT
Nuclear factor erythroid 2-related factor 2 (Nrf2) significantly contributes to drug resistance of cancer cells, and Nrf2 inhibitors have been vigorously pursued. Repurposing of existing drugs, especially anticancer drugs, is a straightforward and promising strategy to find clinically available Nrf2 inhibitors and effective drug combinations. Topoisomerase inhibitors SN-38 (an active metabolite of irinotecan), topotecan, mitoxantrone, and epirubicin were found to significantly suppress Nrf2 transcriptional activity in cancer cells. SN-38, the most potent one among them, significantly inhibited the transcription of Nrf2, as indicated by decreased mRNA level and binding of RNA polymerase II to NFE2L2 gene, while no impact on Nrf2 protein or mRNA degradation was observed. SN-38 synergized with Nrf2-sensitive anticancer drugs such as mitomycin C in killing colorectal cancer cells, and irinotecan and mitomycin C synergistically inhibited the growth of SW480 xenografts in nude mice. Our study identified SN-38 and three other topoisomerase inhibitors as Nrf2 inhibitors, revealed the Nrf2-inhibitory mechanism of SN-38, and indicate that clinically feasible drug combinations could be designed based on their interactions with Nrf2 signaling.
Subject(s)
Antineoplastic Agents , Colorectal Neoplasms , Animals , Mice , Humans , Irinotecan/pharmacology , Camptothecin/pharmacology , Mitomycin/pharmacology , Mice, Nude , NF-E2-Related Factor 2/genetics , Antineoplastic Agents/pharmacology , Drug Resistance, Neoplasm , Topoisomerase Inhibitors/pharmacology , Drug Combinations , Colorectal Neoplasms/drug therapy , Colorectal Neoplasms/geneticsABSTRACT
BACKGROUND: Although hepatitis B virus (HBV) infection is a major risk factor for hepatic cancer, the majority of HBV carriers do not develop this lethal disease. Additional molecular alterations are thus implicated in the process of liver tumorigenesis. Since phosphatase and tensin homolog (PTEN) is decreased in approximately half of liver cancers, we investigated the significance of PTEN deficiency in HBV-related hepatocarcinogenesis. METHODS: HBV-positive human liver cancer tissues were checked for PTEN expression. Transgenic HBV, Alb-Cre and Ptenfl/fl mice were inter-crossed to generate WT, HBV, Pten-/- and HBV; Pten-/- mice. Immunoblotting, histological analysis and qRT-PCR were used to study these livers. Gp73-/- mice were then mated with HBV; Pten-/- mice to illustrate the role of hepatic tumor biomarker golgi membrane protein 73 (GP73)/ golgi membrane protein 1 (GOLM1) in hepatic oncogenesis. RESULTS: Pten deletion and HBV transgene synergistically aggravated liver injury, inflammation, fibrosis and development of mixed hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). GP73 was augmented in HBV; Pten-/- livers. Knockout of GP73 blunted the synergistic effect of deficient Pten and transgenic HBV on liver injury, inflammation, fibrosis and cancer development. CONCLUSIONS: This mixed HCC-ICC mouse model mimics liver cancer patients harboring HBV infection and PTEN/AKT signaling pathway alteration. Targeting GP73 is a promising therapeutic strategy for cancer patients with HBV infection and PTEN alteration.
Subject(s)
Carcinoma, Hepatocellular , Hepatitis B , Liver Neoplasms , PTEN Phosphohydrolase , Animals , Humans , Mice , Carcinoma, Hepatocellular/pathology , Fibrosis , Hepatitis B/complications , Hepatitis B virus , Inflammation/pathology , Liver/pathology , Liver Neoplasms/pathology , Membrane Proteins/metabolism , Mice, Knockout , PTEN Phosphohydrolase/metabolismABSTRACT
Putatively, tooth agenesis was attributed to the initiation failure of tooth germs, though little is known about the histological and molecular alterations. To address if constitutively active FGF signaling is associated with tooth agenesis, we activated Fgf8 in dental mesenchyme with Osr-cre knock-in allele in mice (Osr2-creKI; Rosa26R-Fgf8) and found incisor agenesis and molar microdontia. The cell survival assay showed tremendous apoptosis in both the Osr2-creKI; Rosa26R-Fgf8 incisor epithelium and mesenchyme, which initiated incisor regression from cap stage. In situ hybridization displayed vanished Shh transcription, and immunostaining exhibited reduced Runx2 expression and enlarged mesenchymal Lef1 domain in Osr2-creKI; Rosa26R-Fgf8 incisors, both of which were suggested to enhance apoptosis. In contrast, Osr2-creKI; Rosa26R-Fgf8 molar germs displayed mildly suppressed Shh transcription, and the increased expression of Ectodin, Runx2 and Lef1. Although mildly smaller than WT controls prenatally, the Osr2-creKI; Rosa26R-Fgf8 molar germs produced a miniature tooth with impaired mineralization after a 6-week sub-renal culture. Intriguingly, the implanted Osr2-creKI; Rosa26R-Fgf8 molar germs exhibited delayed odontoblast differentiation and accelerated ameloblast maturation. Collectively, the ectopically activated Fgf8 in dental mesenchyme caused incisor agenesis by triggering incisor regression and postnatal molar microdontia. Our findings reported tooth agenesis resulting from the regression from the early bell stage and implicated a correlation between tooth agenesis and microdontia.
Subject(s)
Fibroblast Growth Factor 8 , Incisor , Mesoderm , Molar , Animals , Fibroblast Growth Factor 8/genetics , Fibroblast Growth Factor 8/metabolism , Mice , Incisor/abnormalities , Incisor/metabolism , Mesoderm/metabolism , Mesoderm/pathology , Molar/abnormalities , Molar/metabolism , Anodontia/genetics , Anodontia/metabolism , Anodontia/pathology , Apoptosis , Hedgehog Proteins/metabolism , Hedgehog Proteins/genetics , Lymphoid Enhancer-Binding Factor 1/metabolism , Lymphoid Enhancer-Binding Factor 1/genetics , Core Binding Factor Alpha 1 Subunit/genetics , Core Binding Factor Alpha 1 Subunit/metabolism , Signal Transduction , Gene Expression Regulation, Developmental , Odontogenesis/genetics , Mice, TransgenicABSTRACT
BACKGROUND: Spiritual care plays a significant role in holistic patient care, addressing not only physical ailments but also attending to patients' emotional and spiritual well-being. While the importance of spiritual care in nursing is widely recognized, there is often a gap in understanding nurses' willingness to provide such care. This cross-sectional study aimed to explore the association between self-efficacy, spiritual well-being, and willingness to provide spiritual care among nursing staff. METHODS: The study conducted a cross-sectional survey of full-time registered nurses at a hospital in Taiwan from January 2019 to December 2019. A sample comprising 168 nurses was selected for participation in the study through a random sampling method. In addition to collecting demographic variables, the assessment tools used in the study include the General Self-Efficacy Scale (GSES) for measuring self-efficacy, the Spiritual Index of Well-Being Chinese Version (SIWB-C) for evaluating spiritual well-being, and the Spiritual Care Needs Inventory (SCNI) to gauge willingness to provide spiritual care. RESULTS: Most participants in the study were female, accounting for 98.2% (n = 165). The mean age of all 168 nurses was 37.1 ± 9.3 years. Additionally, most participants held a Bachelor's degree (79.2%, n = 133) and possessed clinical experience was 10.5 ± 9.3 years. Through logistic regression analysis, it was found that regardless of whether participants have received sufficient spiritual care training, both GSES and SIWB-C remain influential factors in determining the provision of spiritual care. CONCLUSIONS: Collaboration between healthcare management and nursing staff is essential for fostering a healthcare environment that not only appreciates the physical and spiritual dimensions of patient care but also prioritizes the enhancement of nurses ' self-efficacy and well-being.
ABSTRACT
BACKGROUND: Although ß-catenin signaling cascade is frequently altered in human cancers, targeting this pathway has not been approved for cancer treatment. METHODS: High-throughput screening of an FDA-approved drug library was conducted to identify therapeutics that selectively inhibited the cells with activated ß-catenin. Efficacy of iron chelator and mitochondrial inhibitor was evaluated for suppression of cell proliferation and tumorigenesis. Cellular chelatable iron levels were measured to gain insight into the potential vulnerability of ß-catenin-activated cells to iron deprivation. Extracellular flux analysis of mitochondrial function was conducted to evaluate the downstream events of iron deprivation. Chromatin immunoprecipitation, real-time quantitative PCR and immunoblotting were performed to identify ß-catenin targets. Depletion of iron-regulatory protein 2 (IRP2), a key regulator of cellular iron homeostasis, was carried out to elucidate its significance in ß-catenin-activated cells. Online databases were analyzed for correlation between ß-catenin activity and IRP2-TfR1 axis in human cancers. RESULTS: Iron chelators were identified as selective inhibitors against ß-catenin-activated cells. Deferoxamine mesylate, an iron chelator, preferentially repressed ß-catenin-activated cell proliferation and tumor formation in mice. Mechanically, ß-catenin stimulated the transcription of IRP2 to increase labile iron level. Depletion of IRP2-sequered iron impaired ß-catenin-invigorated mitochondrial function. Moreover, mitochondrial inhibitor S-Gboxin selectively reduced ß-catenin-associated cell viability and tumor formation. CONCLUSIONS: ß-catenin/IRP2/iron stimulation of mitochondrial energetics is targetable vulnerability of ß-catenin-potentiated cancer.
Subject(s)
Iron Regulatory Protein 2 , Neoplasms , Mice , Humans , Animals , Iron Regulatory Protein 2/metabolism , beta Catenin/metabolism , Iron/metabolism , Neoplasms/drug therapy , Iron Chelating Agents/pharmacology , Mitochondria/metabolismABSTRACT
BACKGROUND: Studies on chemerin/chemokine-like receptor-1 have mainly focused on adipose and liver with the intestinal tissues largely overlooked. In this study conducted on obese mice, we have explored: 1) CMKLR1 expression in the ileums; 2) CMKLR1 inhibitor α-NETA on body weight and intestinal mucosa integrity hence the impact on hepatic steatosis and pathway involved. METHODS: Nineteen male C57BL/6 mice were randomly divided into five groups: normal diet group (ND), high-fat diet group (HFD), HFD + α-NETA group (NETA), HFD + PD98059 group (PD) and HFD + α-NETA + PD98059 group (NETA + PD). Mice were fed either with a chow diet or HFD for 12 weeks. At 12th week, mice of ND were put on the diet as before; mice of NETA received daily treatments of α-NETA (30 mg/kg) via gavage; mice of PD received daily treatment of PD98059 via tail vein injection; mice of NETA + PD received daily treatment of α-NETA + PD98059, all for another 4 weeks. At the time intervention ended, mice were sacrificed. The body weight, the liver pathologies were assessed. Ileal CMKLR1 mRNA was evaluated by rtPCR; ZO-1, ERK1/2 protein expression of ileal tissues by western blotting; liver TNF-α and serum endotoxin by Elisa. RESULTS: More weight gains in mice of HFD than ND (37.90 ± 3.00 g) vs (24.47 ± 0.50 g), P = 0.002; α-NETA reduced the body weight (33.22 ± 1.90 g) vs (37.90 ± 3.00 g), P = 0.033; and further reduced by NETA + PD98059: (31.20 ± 1.74 g) vs (37.30 ± 4.05 g), P = 0.032. CMKLR1 mRNA expression was up-regulated in ileum in group HFD compared with ND and down-regulated by α-NETA. Steatosis was only alleviated in group PD + NETA with less weight gain. No impact of α-NETA on ileal ZO-1 or pERK with western blotting, and no endotoxin level changes were detected. TNF-α was higher in group HFD than in group ND, while no significant difference between other groups. CONCLUSIONS: CMKLR1 mRNA was up-regulated in the ileum of obese mice and down-regulated by α-NETA along with a body weight control collaborating with ERK inhibitor PD98059. Steatosis was alleviated in a weight dependent way. α-NETA has no influence on intestinal mucosal integrity and no impact on steatohepatitis progression.
Subject(s)
Fatty Liver , Tumor Necrosis Factor-alpha , Male , Animals , Mice , Mice, Obese , Mice, Inbred C57BL , Fatty Liver/drug therapy , Fatty Liver/etiology , Fatty Liver/prevention & control , Liver , Weight Gain , Diet, High-Fat/adverse effects , Intestinal Mucosa , Ileum , Body Weight , Receptors, ChemokineABSTRACT
Although genome-wide association studies (GWASs) have identified over 100 colorectal cancer (CRC) risk loci, an understanding of causal genes or risk variants and their biological functions in these loci remain unclear. Recently, genomic loci 10q26.12 with lead SNP rs1665650 was identified as an essential CRC risk loci of Asian populations. However, the functional mechanism of this region has not been fully clarified. Here, we applied an RNA interfering-based on-chip approach to screen for the genes essential for cell proliferation in the CRC risk loci 10q26.12. Notably, HSPA12A had the most significant effect among the identified genes and functioned as a crucial oncogene facilitating cell proliferation. Moreover, we conducted an integrative fine-mapping analysis to identify putative casual variants and further explored their association with CRC risk in a large-scale Chinese population consisting of 4054 cases and 4054 controls and also independently validated in 5208 cases and 20,832 controls from the UK biobank cohort. We identified a risk SNP rs7093835 in the intron of HSPA12A that was significantly associated with an increased risk of CRC (OR 1.23, 95% CI 1.08-1.41, P = 1.92 × 10-3). Mechanistically, the risk variant could facilitate an enhancer-promoter interaction mediated by the transcriptional factor (TF) GRHL1 and ultimately upregulate HSPA12A expression, which provides functional evidence to support our population findings. Collectively, our study reveals the important role of HSPA12A in CRC development and illustrates a novel enhancer-promoter interaction module between HSPA12A and its regulatory elements rs7093835, providing new insights into the etiology of CRC.
Subject(s)
Colorectal Neoplasms , Genome-Wide Association Study , Humans , Genetic Predisposition to Disease , Promoter Regions, Genetic , Risk , Colorectal Neoplasms/genetics , Polymorphism, Single Nucleotide , Case-Control Studies , HSP70 Heat-Shock Proteins/geneticsABSTRACT
The persistence of Staphylococcus aureus within biofilm can lead to contamination of medical devices and life-threatening infections. Luckily, lactic acid bacteria (LAB) have an inhibitory effect on the growth of these bacteria. This study aims to select LAB strains from fermented vegetables, and analyze their potential inhibition activities against S. aureus. In total, 45 isolates of LAB were successfully isolated from Sichuan pickles, and the CFS of Lactiplantibacillus plantarum LR-14 exerted the strongest inhibitory effect against S. aureus. Moreover, S. aureus cells in planktonic and biofilm states both wrinkled and damaged when treated with the CFS of L. plantarum LR-14. In addition, whole genome sequencing analysis indicates that L. plantarum LR-14 contains various functional genes, including predicted extracellular polysaccharides (EPS) biosynthesis genes, and genes participating in the synthesis and metabolism of fatty acid, implying that L. plantarum LR-14 has the potential to be used as a probiotic with multiple functions.
Subject(s)
Anti-Infective Agents , Fermented Foods , Lactobacillales , Staphylococcal Infections , Anti-Infective Agents/pharmacology , Fatty Acids , Humans , Lactobacillaceae , Lactobacillales/genetics , Polysaccharides/pharmacology , Staphylococcus aureusABSTRACT
Agricultural soil pollution in China poses a major threat to human health and food safety. There are no agricultural soil environmental standards based on human health in China, which prevents effective screening and assessment of risks. Jiangsu (JS) and Zhejiang (ZJ) provinces, located in the Yangtze River Delta (YRD) core region, have obvious differences in agricultural land conditions, which will result in differences in Generic Assessment Criteria (GAC). In this study, we derived and compared human health risk-based GAC using the Contaminated Land Exposure Assessment (CLEA) model for agricultural land scenarios in these two provinces. We found differences in the GAC between JS and ZJ due to differences in parameters. These differences are greatest for benzene, and cadmium (Cd). For Cd, the contribution of oral intake exceeds 90 %, and the vegetable consumption rate and mean daily intake (MDI) may be key parameters affecting GAC. For the volatile organic compound benzene, the inhalation of indoor vapor accounts for about 30 %, and the key parameters affecting the GAC for benzene may be the attenuation factor and soil organic matte (SOM). The derived GAC are generally lager (i.e., less stringent) than the GB15618-2018 and UK Suitable 4 Use Levels (S4ULs); however, the derived GAC for JS and ZJ were lower than the soil screening values (SSV) for residential land in China. This may be related to methods, land use types, and critical receptors. This work will contribute to the development of regional soil environmental standards in China.
Subject(s)
Metals, Heavy , Soil Pollutants , Agriculture , China , Environmental Monitoring , Environmental Pollution/analysis , Humans , Metals, Heavy/analysis , Risk Assessment , Soil , Soil Pollutants/analysisABSTRACT
Cold atmospheric plasma (CAP) has attracted significant attention and has been widely used to inactivate pathogens based on its excellent effect; however, the mechanisms underlying the interactions between plasma-generated species and organisms have not yet been fully elucidated. In this paper, the interactions of reactive oxygen plasma species (O, OH and H2O2) with chitin polymer (the skeletal component of the Candida albicans cell wall) were investigated by means of reactive molecular dynamics simulations from a microscopic point of view. Our simulations show that O and OH species can break important structural bonds (e.g., N-H bonds, O-H bonds and C-H bonds) of chitin. This is followed by a cascade of bond cleavage and double bond formation events. This simulation study aimed to improve the understanding of the micromechanism of plasma-inactivated Candida albicans at the atomic level.
Subject(s)
Candida albicans/drug effects , Candidiasis/drug therapy , Cell Wall/drug effects , Chitin/metabolism , Plasma Gases/pharmacology , Reactive Oxygen Species/metabolism , Candida albicans/chemistry , Candida albicans/metabolism , Candidiasis/metabolism , Candidiasis/microbiology , Hydrogen Peroxide/chemistry , Hydrogen Peroxide/pharmacology , Molecular Dynamics SimulationABSTRACT
Host nutrition is an important factor affecting disease progression. Selenium (Se) is an essential trace element for the human body with anti-inflammatory, antioxidant, and immune effects, and Se deficiency increases RNA-virus replication and virulent mutations, which lead to more severe tissue damage and symptoms. Low Se status in the host may be an important cause of health complications induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this article, we describe the metabolic mechanisms by which Se is involved in anti-inflammatory, antioxidant, and immune effects, and review the role and clinical effects of Se in viral infection. We then discuss the potential relationship between Se and coronavirus disease 2019 (COVID-19). The association between soil Se level and the incidence of COVID-19 was observed in different cities of Hubei Province. The incidence of COVID-19 was more than 10 times lower in Se-enriched cities (Enshi, Shiyan, and Xiangyang) than in Se-deficient cities (Suizhou and Xiaogan). Although the relationship between soil Se levels and the incidence of COVID-19 in Hubei still needs further study, these findings provide baseline information demonstrating the effect of Se levels on SARS-CoV-2, which could contribute to the prevention and management of COVID-19.
Subject(s)
COVID-19 , Selenium , Virus Diseases , Humans , Nutritional Status , SARS-CoV-2ABSTRACT
Based on 1677 published studies, 1648 sites across China collected from 1985 to 2016 were used to research the concentrations of arsenic in agricultural soils. In order to understand the status of arsenic pollution in agricultural soils in China over the past three decades, and to learn about the arsenic stocks in agricultural soils in various regions, and compared the relationship with annual arsenic emissions in China, and finally evaluated the potential ecological risks and human health risks. The median arsenic concentration in the surface agricultural soils of China was 10.40 mg Kg-1, and it ranged from 0.4 mg Kg-1 to 175.8 mg Kg-1. The inventory of arsenic in Chinese agricultural surface soils was estimated to be 3.71 × 106 t. In this study, the arsenic concentrations were found to be higher in Central, South, and Southwest China than those in other regions. The trend of arsenic pollution in agricultural soils has gradually increased over the past three decades. However, the growth rate of arsenic concentrations pollution in farmlands agricultural in China slowed during 2012-2016. The ecological risk index and geoaccumulation index revealed that arsenic in Chinese agricultural soil poses a low risk to the ecosystem. For human health assessment, the dietary pathway was the main pathway of exposure to arsenic in farmland soil of China. However, children's soil intake also contributed 34.48% to the exposure to arsenic, owing to their behavior. This study can provide a reference for the management of arsenic agricultural pollution in farmland soils in China.
Subject(s)
Arsenic , Metals, Heavy , Soil Pollutants , Agriculture , Arsenic/analysis , Child , China , Ecosystem , Environmental Monitoring , Humans , Metals, Heavy/analysis , Risk Assessment , Soil , Soil Pollutants/analysisABSTRACT
Soil contamination with mercury (Hg) is a serious and widespread issue in China, with particularly severe effects on the quality of agricultural soils. To analyse long-term, nation-wide trends in Hg contamination of agriculture soil, we conducted a review of Hg concentrations in agricultural soils over four decades, based on 791 studies comprising 1411 sites, published between 1976 and 2016. We assessed spatiotemporal variations in Hg concentration, along with ecological and health risks. While Hg concentrations in agricultural soils showed an increasing trend between 1979 and 2010, they declined thereafter. Moreover, Hg concentrations in agricultural soils were generally high in western (e.g. Guizhou), southern (e.g. Hunan) and north-eastern provinces (e.g. Liaoning), where mining activities were concentrated. Using the geoaccumulation index (Igeo) and other ecological and health risk indices, we found most sampling sites to be uncontaminated, or to have a low level of contamination, although some mining sites showed moderate to extreme Hg contamination. The noncarcinogenic risk to exposure groups followed the order of children (4.42) > adult females (2.71) > adult males (2.45). Therefore, children were identified as the priority risk group. Noncarcinogenic risk values exceeded 100 in some areas in Guizhou and Hunan provinces; these areas should be prioritised for Hg control measures. This review examined Hg pollution in Chinese agricultural soils to provide insight to policymakers for the development of targeted contamination prevention measures.
Subject(s)
Agriculture , Environmental Exposure/analysis , Mercury/analysis , Soil Pollutants/analysis , China , Environmental Monitoring , Humans , Mining , Risk AssessmentABSTRACT
BACKGROUND: Little is known about the gaps between expectation and the perception of service quality in the care setting of prolonged mechanical ventilation (MV). METHODS: We conducted this prospective study at the Respiratory Care Center (RCC) of a medical center from February 2017 to January 2018. Family members of the patients admitted to the RCC completed a questionnaire based on the SERVQUAL instrument in two sections - expectation and perception, consisting of 22 questions each in five dimensions. We analyzed the gaps between paired items, used important-performance analysis (IPA) to identify priority items for improvement, and performed multivariate logistic regression analysis. RESULTS: A total of 167 respondents participated in the survey. The average length of patient stay in the RCC was 19.4 days, and 70.7% were successfully liberated from MV. The overall mean SERVQUAL scores for the two sections were similar (4.50 ± 0.52 and 4.51 ± 0.54 for expectation and perception, respectively; p = 0.808). IPA identified four items, including one "tangible," one "reliability" and two "empathy" with an undesired expectation/perception gap indicating a priority for improvement. Multivariate logistic regression analysis showed that male respondents, patients older than 75 years, tracheostomy, and the need for physical training or dialysis were associated with an increased gap in these priority items. CONCLUSION: Gaps exist between expectation and perception in multiple dimensions of the quality of healthcare service in the care setting of prolonged MV, indicating unmet needs and priorities for improvement.
Subject(s)
Patient Satisfaction/statistics & numerical data , Quality of Health Care , Respiration, Artificial/standards , Surveys and Questionnaires , Adult , Aged , Aged, 80 and over , Female , Hospitals, University , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Perception , Prospective Studies , Reproducibility of Results , Respiration, Artificial/psychology , Taiwan , Young AdultABSTRACT
AIM: The purpose of this pilot study was to evaluate the effects of the Bass brushing method on dental plaque and pneumonia in older adults hospitalized with pneumonia after discharge. BACKGROUND: Poor oral hygiene may lead to pneumonia. Complications of pneumonia in older adults can be life-threatening during hospitalization and after discharge. METHODS: Older adults hospitalized with pneumonia (nâ¯=â¯30) were randomly assigned to intervention (with the Bass brushing method; nâ¯=â¯15) or control (with usual care; nâ¯=â¯15) groups. Dental plaque index and pneumonia as detected on chest x-rays were evaluated prior to the intervention (baseline) and every month for six months after discharge. RESULTS: Participants in the intervention group experienced a sustained reduction in dental plaque from the fourth to the sixth months (pâ¯=â¯.024; pâ¯=â¯.025; pâ¯=â¯.000, respectively) that was not found in the control group. There were no group differences in detected pneumonia throughout the follow-up period. Pneumonia as detected on the chest x-rays at baseline (pâ¯=â¯.001) and dental plaque index (pâ¯=â¯.021) were significant predictors of the risk of pneumonia across groups. CONCLUSIONS: The Bass brushing method is a simple and effective oral hygiene practice that reduces dental plaque in older adults hospitalized with pneumonia after discharge.
Subject(s)
Dental Plaque/prevention & control , Oral Hygiene/methods , Pneumonia/prevention & control , Toothbrushing/methods , Aged , Aged, 80 and over , Dental Plaque Index , Female , Humans , Longitudinal Studies , Male , Pilot ProjectsABSTRACT
BACKGROUND: Spiritual well-being has become an increasingly important issue for the elderly people. The 12-item Spirituality Index of Well-Being (SIWB) is a well-validated instrument for assessing a patient's current spiritual state. However, the psychometric properties of the SIWB in the Chinese elderly populations are not known. Therefore, this study translated the SIWB into Chinese and evaluated its psychometric properties. METHODS: The English version of the SIWB was first translated into Chinese based on the Brislin's translation model. The psychometric properties of the translated version of the SIWB (SIWB-C) was evaluated in 416 elderly Taiwanese recruited using a purposive sampling procedure from a medical center, a long-term care institution, and a community health center. Convergent validity was accessed using Pearson's correlation coefficients of the SIWB-C, the EQ-5D-3 L health-related quality of life scale, and the Geriatric Depression Scale-5 (GDS-5). Exploratory factor analysis with Varimax rotation was performed to determine the construct validity. Confirmatory factor analysis was conducted for verification of the quality of the factor structures and demonstrating the convergent validity of the SIWB-C. An internal consistency test based on the Cronbach's alpha coefficient and a stability test based on the Guttman split-half coefficient were also performed. Test-retest reliability was evaluated with intraclass correlation coefficient. RESULTS: Exploratory factor analysis confirmed the original two-dimensional structure of the scale. Confirmatory factor analysis indicated a well-fitting model and a fine convergent validity of the SIWB-C. The Cronbach's alpha coefficient and the Guttman split-half coefficient for the SIWB-C were 0.94 and 0.84, respectively. The correlations between the SIWB-C with EQ-5D-3 L and GDS-5 were 0.22 (p < 0.01) and 0.45 (p < 0.05), respectively. The intraclass correlation coefficient of the SIWB-C over a test-retest interval of two weeks was 0.989. CONCLUSIONS: The SIWB-C was found to be a potential useful measure of subjective spiritual well-being in elderly Taiwanese. Its application in assessing the spiritual well-being in Mandarin-speaking elderly population warrants further investigation.
Subject(s)
Health Services for the Aged , Psychometrics/methods , Spirituality , Aged , Aged, 80 and over , Asian People , Factor Analysis, Statistical , Female , Humans , Long-Term Care , Male , Quality of Life , Reproducibility of Results , TaiwanABSTRACT
BACKGROUND: Late-life depression is common among elderly patients. Ignorance of the health problem, either because of under-diagnosis or under-treatment, causes additional medical cost and comorbidity. For a better health and quality of life (QoL), evaluation, prevention and treatment of late-life depression in elderly patients is essential. METHODS: This study examined (1) the differences of clinical characteristics, degree of improvement on QoL and functionality on discharge between non-depressed and depressed elderly inpatients and (2) factors associated with QoL on discharge. Four hundred and seventy-one elderly inpatients admitted to a geriatric evaluation and management unit (GEMU) from 2009 to 2010 were enrolled in this study. Comprehensive geriatric assessment including the activities of daily living (ADL), geriatric depression scale, and mini-mental state examination were conducted. QoL was assessed using the European Quality of Life-5 Dimensions and the European Quality of Life-5 Dimensions Visual Analog Scale on discharge. Information on hospital stay and Charlson comorbidity index were obtained by chart review. Chi-square tests, independent t-tests, Mann-Whitney U tests and multiple linear regressions were used in statistical analysis. RESULTS: Worse QoL and ADL on discharge were found among the depressed. Depressive symptoms, female gender, duration of hospital stay, and rehabilitation were significant factors affecting QoL on discharge in linear regression models. CONCLUSIONS: The importance of the diagnosis and treatment of depression among elderly inpatients should not be overlooked during hospital stay and after discharge. Greater efforts should be made to improve intervention with depressed elderly inpatients.