Central Environmental Protection Inspection (CEPI) is an important innovative measure meant to improve the health of China’s environment. In view of this, based on the "quasi natural experiment" ...situation of the implementation of CEPI in China, this paper takes as its research sample 155 A-share listed companies located in the provinces in which CEPI was first implemented. Our work uses the event study method to explore the reaction of China’s capital market to this policy implementation. The results show two significant findings. (1) CEPI will cause the capital market to react negatively because of the environmental protection pressure that it brings to bear on corporations; that is, the capital market will experience significantly negative abnormal returns due to the signals sent by CEPI. (2) Further analysis shows that the multiple heterogeneity factors will have an impact on the capital market’s reaction to CEPI. Specifically, at the corporate level, we find that firms that cause heavy pollution, firms that are small-scale, and firms with weak political connections are more sensitive to the market’s reaction to the CEPI policy; at the regional levels, the effect is more significant in areas with high environmental performance.
•Research empirically tests the capital market’s reaction to China’s CEPI policy in 2016 using the event study method.•The capital market experiences significantly negative abnormal returns due to the signals sent by CEPI.•Research analyzes the multiple heterogeneity factors at the corporate and regional levels.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Objective
Ovarian cancer (OC) affects nearly 22,000 women annually in the United States and ranks fifth in cancer deaths, largely because of being diagnosed at an advanced stage. Autophagy is the ...cellular process of self-degrading damaged or degenerate proteins and organelles. Long non-coding RNAs (lncRNAs) are a group of RNA molecules whose transcripts are greater than 200 nt but are not translated into proteins. However, just a small number of autophagy-related lncRNAs have been explored in depth.
Methods
We used RNA sequencing data from The Cancer Genome Atlas (TCGA) and autophagy datasets to identify dysfunctional autophagy-related lncRNAs and provide potential useful biomarkers for OC diagnosis and prognosis.
Results
Seventeen differentially expressed lncRNAs (AC010186.3, AC006001.2, LBX2-AS1, SNHG17, AC011445.1, AC083880.1, MIR193BHG, AC025259.3, HCG14, AC007114.1, AC108673.2, USP30-AS1, AC010336.5, LINC01132, AC006333.2, LINC00665 and AC027348.1) were selected as independent prognostic factors for OC patients. Functional annotation of the data was performed through gene set enrichment analysis (GSEA). The results suggested that the high-risk group was mainly enriched in specific tumor-related and metabolism pathways.
Conclusion
Based on the online databases, we identified novel autophagy-related lncRNAs for the prognosis of ovarian cancer.
The molecular mechanisms involved in the development of obesity and related complications remain unclear. Here, we report that obese mice and human subjects have increased activity of neutrophil ...elastase (NE) and decreased serum levels of the NE inhibitor α1-antitrypsin (A1AT, SerpinA1). NE null (Ela2−/−) mice and A1AT transgenic mice were resistant to high-fat diet (HFD)-induced body weight gain, insulin resistance, inflammation, and fatty liver. NE inhibitor GW311616A reversed insulin resistance and body weight gain in HFD-fed mice. Ela2−/− mice also augmented circulating high molecular weight (HMW) adiponectin levels, phosphorylation of AMP-activated protein kinase (AMPK), and fatty acid oxidation (FAO) in the liver and brown adipose tissue (BAT) and uncoupling protein (UCP1) levels in the BAT. These data suggest that the A1AT-NE system regulates AMPK signaling, FAO, and energy expenditure. The imbalance between A1AT and NE contributes to the development of obesity and related inflammation, insulin resistance, and liver steatosis.
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► Obese men and mice have decreased serum A1AT levels and increased NE activity ► Neutrophil infiltration and NE deposition occur in adipose tissue from HFD-fed mice ► NE−/− and A1AT Tg mice have reduced HFD-induced insulin resistance and inflammation ► NE deletion increases AMPK signaling and fatty acid oxidation in liver and BAT
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•An epoxy resin-Q345 system with a sandwich structure was prepared.•Cl− ions permeated into epoxy resin coating prior to K+ ions.•Free volume size and PAL increased when the coating was immersed into ...the solution.
An epoxy resin coating with a sandwich structure was prepared to investigate ion transport behavior in the coating. The macro- and micro- appearance of the coating immersed in 5wt.% KCl solutions was observed by stereomicroscopy, scanning electron microscopy equipped with an energy dispersive spectrometer. The electrochemical property of the coating was characterized by electrochemical impedance spectroscopy, and change of free volume after immersion was characterized by positron annihilation lifetime spectroscopy. The results indicated that Cl− ions permeated into the coating prior to K+ ions, the free volume size and positron annihilation lifetime of the coating increased during immersion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Disordered metabolic states, which are characterised by hypoxia and elevated levels of metabolites, particularly lactate, contribute to the immunosuppression in the tumour microenvironment (TME). ...Excessive lactate secreted by metabolism-reprogrammed cancer cells regulates immune responses via causing extracellular acidification, acting as an energy source by shuttling between different cell populations, and inhibiting the mechanistic (previously ‘mammalian’) target of rapamycin (mTOR) pathway in immune cells. This review focuses on recent advances in the regulation of immune responses by lactate, as well as therapeutic strategies targeting lactate anabolism and transport in the TME, such as those involving glycolytic enzymes and monocarboxylate transporter inhibitors. Considering the multifaceted roles of lactate in cancer metabolism, a comprehensive understanding of how lactate and lactate-targeting therapies regulate immune responses in the TME will provide insights into the complex relationships between metabolism and antitumour immunity.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Interferon-α2b Treatment for COVID-19 Zhou, Qiong; Chen, Virginia; Shannon, Casey P ...
Frontiers in immunology,
05/2020, Volume:
11
Journal Article
Peer reviewed
Open access
The global pandemic of COVID-19 cases caused by infection with SARS-CoV-2 is ongoing, with no approved antiviral intervention. We describe here the effects of treatment with interferon (IFN)-α2b in a ...cohort of confirmed COVID-19 cases in Wuhan, China. In this uncontrolled, exploratory study, 77 adults hospitalized with confirmed COVID-19 were treated with either nebulized IFN-α2b (5 mU b.i.d.), arbidol (200 mg t.i.d.) or a combination of IFN-α2b plus arbidol. Serial SARS-CoV-2 testing along with hematological measurements, including cell counts, blood biochemistry and serum cytokine levels, and temperature and blood oxygen saturation levels, were recorded for each patient during their hospital stay. Treatment with IFN-α2b with or without arbidol significantly reduced the duration of detectable virus in the upper respiratory tract and in parallel reduced duration of elevated blood levels for the inflammatory markers IL-6 and CRP. These findings suggest that IFN-α2b should be further investigated as a therapy in COVID-19 cases.
MiRNAs are involved in the occurrence and development of many diseases. Extensive literature studies have demonstrated that miRNA-disease associations are stratified and encompass ~ 20% causal ...associations. Computational models that predict causal miRNA-disease associations provide effective guidance in identifying novel interpretations of disease mechanisms and potential therapeutic targets. Although several predictive models for miRNA-disease associations exist, it is still challenging to discriminate causal miRNA-disease associations from non-causal ones. Hence, there is a pressing need to develop an efficient prediction model for causal miRNA-disease association prediction.
We developed DNI-MDCAP, an improved computational model that incorporated additional miRNA similarity metrics, deep graph embedding learning-based network imputation and semi-supervised learning framework. Through extensive predictive performance evaluation, including tenfold cross-validation and independent test, DNI-MDCAP showed excellent performance in identifying causal miRNA-disease associations, achieving an area under the receiver operating characteristic curve (AUROC) of 0.896 and 0.889, respectively. Regarding the challenge of discriminating causal miRNA-disease associations from non-causal ones, DNI-MDCAP exhibited superior predictive performance compared to existing models MDCAP and LE-MDCAP, reaching an AUROC of 0.870. Wilcoxon test also indicated significantly higher prediction scores for causal associations than for non-causal ones. Finally, the potential causal miRNA-disease associations predicted by DNI-MDCAP, exemplified by diabetic nephropathies and hsa-miR-193a, have been validated by recently published literature, further supporting the reliability of the prediction model.
DNI-MDCAP is a dedicated tool to specifically distinguish causal miRNA-disease associations with substantially improved accuracy. DNI-MDCAP is freely accessible at http://www.rnanut.net/DNIMDCAP/ .
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Three new polyether‐tethered dinickel–salphen complexes (2 a–c) have been synthesized and fully characterized by NMR spectroscopy, mass spectrometry, and elemental analyses. The binding affinity and ...selectivity of these complexes and of the parent mono‐nickel complex (1) towards dimeric quadruplex DNA have been determined by UV/Vis titrations, fluorescence spectroscopy, CD spectroscopy, and electrophoresis. These studies have shown that the dinickel–salphen complex with the longest polyether linker (2 c) has higher binding affinity and selectivity towards dimeric quadruplexes (over monomeric quadruplexes) than the dinickel–salphen complexes with the shorter polyether linkers (2 a and 2 b). Complex 2 c also has higher selectivity towards human telomeric dimeric quadruplexes with one TTA linker than the monometallic complex 1. Based on the spectroscopic data, a possible binding mode between complex 2 c and the dimeric G‐quadruplex DNA under study is proposed.
A dinuclear metal complex based on nickel–salphens that binds with high affinity and selectivity to dimeric G‐quadruplex DNA structures is reported. The ligand–DNA interactions have been investigated using a range of spectroscopic techniques. This type of dimetallic complex could have interesting applications in targeting sequential G‐quadruplex DNA sequences proposed to be present in telomeric DNA.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Sarcopenia is a common disorder that leads to a progressive decrease in skeletal muscle function in elderly people. Exercise effectively prevents or delays the onset and progression of sarcopenia. ...However, the molecular mechanisms underlying how exercise intervention improves skeletal muscle atrophy remain unclear. In this study, we found that 21‐month‐old zebrafish had a decreased swimming ability, reduced muscle fibre cross‐sectional area, unbalanced protein synthesis, and degradation, increased oxidative stress, and mitochondrial dysfunction, which suggests zebrafish are a valuable model for sarcopenia. Eight weeks of exercise intervention attenuated these pathological changes in sarcopenia zebrafish. Moreover, the effects of exercise on mitochondrial dysfunction were associated with the activation of the AMPK/SIRT1/PGC‐1α axis and 15‐PGDH downregulation. Our results reveal potential therapeutic targets and indicators to treat age‐related sarcopenia using exercise intervention.
Exercise reduce zebrafish sarcopenia may by activating the AMPK/SIRT1/PGC‐1α axis and down‐regulating 15‐PGDH to improve mitochondrial function. Aging induces oxidative stress and mitochondrial dysfunction in skeletal muscle, reducing myofibre cross‐sectional area, imbalance in protein synthesis and degradation, and, ultimately, muscle atrophy. Exercise inhibited oxidative stress and improved mitochondrial function may via AMPK/SIRT1/PGC‐1α axis activation and 15‐PGDH downregulation, effectively preventing age‐related sarcopenia (Created with BioRender.com.).
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
Mitochondria are vital organelles in cells, regulating energy metabolism and apoptosis. Mitochondrial transcellular transfer plays a crucial role during physiological and pathological conditions, ...such as rescuing recipient cells from bioenergetic deficit and tumorigenesis. Studies have shown several structures that conduct transcellular transfer of mitochondria, including tunneling nanotubes (TNTs), extracellular vesicles (EVs), and Cx43 gap junctions (GJs). The intra- and intercellular transfer of mitochondria is driven by a transport complex. Mitochondrial Rho small GTPase (MIRO) may be the adaptor that connects the transport complex with mitochondria, and myosin XIX is the motor protein of the transport complex, which participates in the transcellular transport of mitochondria through TNTs. In this review, the roles of TNTs, EVs, GJs, and related transport complexes in mitochondrial transcellular transfer are discussed in detail, as well as the formation mechanisms of TNTs and EVs. This review provides the basis for the development of potential clinical therapies targeting the structures of mitochondrial transcellular transfer.