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OBJECTIVES: To assess the efficacy and tolerability of iGlarLixi-a novel, fixed-ratio, soluble combination of insulin glargine and lixisenatide-for the treatment of type 2 diabetes (T2D). METHODS: The PubMed, Embase, Cochrane Library and ClinicalTrials.gov databases were searched from inception to November 15, 2023 to identify randomized controlled trials (RCTs) comparing iGlarLixi with a placebo or any other antidiabetic agent in adults with T2D. Risk ratios (RRs) and mean differences (MDs) with 95% confidence intervals (CIs) were calculated to evaluate the outcomes. RESULTS: A total of 10 trials enrolling 6071 T2D patients were included. Compared with placebos or other antidiabetic agents, iGlarLixi exerted beneficial effects on changes in HbA1c, the percentage of patients who achieved an HbA1c < 7%, the percentage of patients who achieved an HbA1c < 6.5%, the percentage of patients who achieved an HbA1c < 7.0% without weight gain and/or without severe or blood glucose-confirmed hypoglycemic episodes, changes in fasting plasma glucose, and changes in self-measured plasma glucose. Regarding safety, iGlarLixi did not increase the incidence of severe hypoglycemia or serious adverse events but did increase the incidence of gastrointestinal adverse events, symptomatic hypoglycemia, and adverse events (e.g., nausea, vomiting, diarrhea). CONCLUSIONS: iGlarLixi showed improved efficacy and safety in patients with T2D. Additional large, multicenter RCTs are warranted to obtain deeper insights into the efficacy and safety of iGlarLixi, thereby providing guidance for clinical treatment decisions.
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The use of tyrosine kinase inhibitors (TKIs) has resulted in significant occurrence of arrhythmias. However, the precise mechanism of the proarrhythmic effect is not fully understood. In this study, we found that nilotinib (NIL), vandetanib (VAN), and mobocertinib (MOB) induced the development of "cellrhythmia" (arrhythmia-like events) in a concentration-dependent manner in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Continuous administration of NIL, VAN, or MOB in animals significantly prolonged the action potential durations (APD) and increased susceptibility to arrhythmias. Using phosphoproteomic analysis, we identified proteins with altered phosphorylation levels after treatment with 3⯵M NIL, VAN, and MOB for 1.5â¯h. Using these identified proteins as substrates, we performed kinase-substrate enrichment analysis to identify the kinases driving the changes in phosphorylation levels of these proteins. MAPK and WNK were both inhibited by NIL, VAN, and MOB. A selective inhibitor of WNK1, WNK-IN-11, induced concentration- and time-dependent cellrhythmias and prolonged field potential duration (FPD) in hiPSC-CMs in vitro; furthermore, administration in guinea pigs confirmed that WNK-IN-11 prolonged ventricular repolarization and increased susceptibility to arrhythmias. Fingding indicated that WNK1 inhibition had an in vivo and in vitro arrhythmogenic phenotype similar to TKIs. Additionally,three of TKIs reduced hERG and KCNQ1 expression at protein level, not at transcription level. Similarly, the knockdown of WNK1 decreased hERG and KCNQ1 protein expression in hiPSC-CMs. Collectively, our data suggest that the proarrhythmic effects of NIL, VAN, and MOB occur through a kinase inhibition mechanism. NIL, VAN, and MOB inhibit WNK1 kinase, leading to a decrease in hERG and KCNQ1 protein expression, thereby prolonging action potential repolarization and consequently cause arrhythmias.
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Potenciales de Acción , Arritmias Cardíacas , Miocitos Cardíacos , Piperidinas , Proteómica , Pirimidinas , Quinazolinas , Humanos , Arritmias Cardíacas/inducido químicamente , Animales , Proteómica/métodos , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Piperidinas/farmacología , Piperidinas/toxicidad , Pirimidinas/toxicidad , Pirimidinas/farmacología , Quinazolinas/toxicidad , Quinazolinas/farmacología , Potenciales de Acción/efectos de los fármacos , Inhibidores de Proteínas Quinasas/toxicidad , Inhibidores de Proteínas Quinasas/farmacología , Fosforilación , Canal de Potasio ERG1/metabolismo , Canal de Potasio ERG1/antagonistas & inhibidores , Canal de Potasio ERG1/genética , Cobayas , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/metabolismo , Masculino , Canal de Potasio KCNQ1/metabolismo , Canal de Potasio KCNQ1/genética , Canal de Potasio KCNQ1/efectos de los fármacos , Fosfoproteínas/metabolismo , Relación Dosis-Respuesta a DrogaRESUMEN
The differences in the safety and efficacy of anticoagulation between different types of new oral anticoagulants(NOACs) and low molecular weight heparin(LMWH) are still controversial. The main purposes of this study were to analyze safety and efficacy of NOACs versus LMWH for thromboprophylaxis, and perform subgroup analyses stratified by individual NOACs and different populations after total hip arthroplasty (THA) or total knee arthroplasty (TKA). Literature search was performed in PubMed, EMBASE, Cochrane Library, CNKI and Wanfang databases until June 31, 2022. This systematic review and meta-analysis included 46 randomized controlled trials (RCT) with 39, 924 patients. We evaluated the safety and efficacy of thromboprophylaxis between LMWH and NOACs. NOACs were more effective in reducing deep vein thrombosis (DVT) (RR0.59; 95%CI 0.49-0.71) and adverse events (RR: 0.96; 95%CI: 0.93-0.99) than LMWH. The subgroup analyses for different anticoagulants revealed that rivaroxaban (RR:0.49; 95%CI:0.36-0.66), apixaban (RR: 0.54; 95%CI: 0.36-0.81) and edoxaban (RR:0.49; 95%CI: 0.32-0.75) have the lower risk of DVT than LMWH. Apixaban (RR:0.89; 95%CI: 0.80-1.00) had superior prevention of bleeding to LMWH. Edoxaban exhibited a lower risk of VTE (RR: 0.46; 95%CI: 0.33-0.65), advantage events (RR: 0.87; 95%CI: 0.82-0.93), and drug-related adverse events (DRAEs) (RR: 0.64; 95%CI: 0.53-0.76) than LMWH. East Asian population was superior to western population for preventing DVT, advantage events, and DRAE using NOACs. In conclusion, NOACs are more effective than LMWH at preventing DVT and adverse events after arthroplasty. Apixaban has lower bleeding than LMWH, and East Asian populations may benefit more than western population from NOACs.
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BACKGROUND: Currently, endoplasmic reticulum stress is studied utilizing a dephosphorylation inhibitor (Sal). The traditional Chinese patent medicine and simple formulation Shensong Yangxin Capsule is a commonly used medication for the treatment of arrhythmia. However, the efficacy and underlying mechanism of the capsule in treating post-ischemic heart failure in myocardial tissue have not yet been investigated. OBJECTIVE: The therapeutic effects and the underlying mechanism of the Shensong Yangxin Capsule (SSYX) and the dephosphorylation inhibitor Salubrinal (Sal) on heart failure (HF) induced by high-intensity exercise in rats with acute myocardial infarction (AMI) were investigated. METHODS: Male infants of 8 weeks Spragge-Dawley (SD) rats were randomly assigned to one of four groups: sham surgery group, AMI+placebo group, AMI+Shensong Yangxin Capsule group (AMI+SSYX), and AMI+Sal administration group. Rats' myocardial infarction was induced by left coronary artery ligation. Rats were subjected to a 3-week high-intensity exercise program to simulate heart failure after 7 days of postoperative rest. After the fourth postoperative week, echocardiography was applied to determine the left ventricular ejection fraction (LVEF), left ventricular fractional shortening (LVFS), and left ventricular systolic volume (LVESV) in each group. HE and TUNEL labeling were employed to examine the morphology of cardiac cells and measure the percentage of apoptosis in each group; Western blotting was applied to detect the cardiomyocyte apoptosis-related proteins p-JNK, p-P38, and NOX2, while ELISA was used to detect glutathione(GSH), malondialdehyde (MDA), and superoxide dismutase (SOD) in serum. RESULTS: Following a 4-week drug intervention:(1)LVFS and LVEF in the AMI+placebo group were statistically significantly reduced, while LVESV were significantly higher, compared to those in the sham surgery group (P<0.05); The AMI+SSYX group performed statistically significantly better than the AMI+placebo group(P<0.05). (2) The myocardial cells in the AMI+placebo group exhibited significant swelling and inflammatory cell infiltration; the myocardial cells in the AMI+SSYX group and AMI+Sal group displayed mild swelling and minimal inflammatory cell infiltration; the AMI+SSYX group's myocardial cell morphology was superior to that of the AMI+Sal group; (3) The apoptosis rate of the AMI+placebo group was around 95%, greater than that of the sham surgery group (2.55%). The apoptosis rate of the AMI+SSYX group is approximately 21%, while the apoptosis rate of the AMI+Sal group is about 43%. (4) In the AMI+placebo group, p-JNK, p-P38, and NOX2 protein expression dramatically increased compared to the sham surgery group. The expression of p-P38, NOX2, and p-JNK/t-JNK was considerably reduced in the AMI+Shensong group and AMI+Sal group, compared to the AMI+placebo group. (P<0.01)The AMI+SSYX group's result is superior to that of the AMI+Sal group. (5) Compared to the sham surgery group, the serum levels of SOD and GSH were significantly lower, and MDA was significantly higher in the AMI+placebo group. Compared to the AMI+placebo group, the serum levels of SOD and GSH were significantly higher, and MDA was significantly lower in the AMI+SSYX group and the AMI+Sal group. (P<0.05) Conclusion: In rats with acute myocardial infarction in high-intensity exercise-induced heart failure, Shensong Yangxin Capsule dramatically reduces myocardial cell death and cardiac dysfunction. SSYX has a shorter course of treatment and a better therapeutic effect than Sal.
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Cápsulas , Medicamentos Herbarios Chinos , Insuficiencia Cardíaca , Infarto del Miocardio , Ratas Sprague-Dawley , Animales , Infarto del Miocardio/tratamiento farmacológico , Masculino , Insuficiencia Cardíaca/tratamiento farmacológico , Ratas , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/administración & dosificación , Cinamatos/farmacología , Cinamatos/química , Medicina Tradicional China , Apoptosis/efectos de los fármacosRESUMEN
S1P, also referred to as sphingosine-1-phosphate, is a lipid molecule with bioactive properties involved in numerous cellular processes such as cell growth, movement, programmed cell death, self-degradation, cell specialization, aging, and immune system reactions. Autophagy is a meticulously controlled mechanism in which cells repurpose their elements to maintain cellular balance. There are five stages in autophagy: initiation, nucleation, elongation and maturation, fusion, and degradation. New research has provided insight into the complex connection between S1P and autophagy, uncovering their interaction in both normal and abnormal circumstances. Gaining knowledge about the regulatory mechanism of S1P signaling on autophagy can offer a valuable understanding of its function in well-being and illness, potentially leading to innovative therapeutic concepts for diverse ailments. Hence, this review analyzes the essential stages in mammalian autophagy, with a specific emphasis on recent research exploring the control of each stage by S1P. Additionally, it sheds light on the roles of S1P-induced autophagy in various disorders.
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Inflammatory Bowel Disease (IBD), a chronic nonspecific intestinal inflammatory disease, is comprised of Ulcerative Colitis (UC) and Crohn's Disease (CD). IBD is closely related to a systemic inflammatory reaction and affects the progression of many intestinal and extraintestinal diseases. As one of the representative bacteria for probiotic-assisted therapy in IBD, multiple strains of Lactobacillus have been proven to alleviate intestinal damage and strengthen the intestinal immunological barrier, epithelial cell barrier, and mucus barrier. Lactobacillus also spares no effort in the alleviation of IBD-related diseases such as Colitis-associated Colorectal cancer (CAC), Alzheimer's Disease (AD), Depression, Anxiety, Autoimmune Hepatitis (AIH), and so on via gut-brain axis and gut-liver axis. This article aims to discuss the role of Lactobacillus in IBD and IBD-related diseases, including its underlying mechanisms and related curative strategies from the present to the future.
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Sunitinib (SNT)-induced cardiotoxicity is associated with abnormal calcium regulation caused by phosphoinositide 3 kinase inhibition in the heart. Berberine (BBR) is a natural compound that exhibits cardioprotective effects and regulates calcium homeostasis. We hypothesized that BBR ameliorates SNT-induced cardiotoxicity by normalizing the calcium regulation disorder via serum and glucocorticoid-regulated kinase 1 (SGK1) activation. Mice, neonatal rat cardiomyocytes (NRVMs), and human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were used to study the effects of BBR-mediated SGK1 activity on the calcium regulation disorder caused by SNT as well as the underlying mechanism. BBR offered prevention against SNT-induced cardiac systolic dysfunction, QT interval prolongation, and histopathological changes in mice. After the oral administration of SNT, the Ca2+ transient and contraction of cardiomyocytes was significantly inhibited, whereas BBR exhibited an antagonistic effect. In NRVMs, BBR was significantly preventive against the SNT-induced reduction of calcium transient amplitude, prolongation of calcium transient recovery, and decrease in SERCA2a protein expression; however, SGK1 inhibitors resisted the preventive effects of BBR. In hiPSC-CMs, BBR pretreatment significantly prevented SNT from inhibiting the contraction, whereas coincubation with SGK1 inhibitors antagonized the effects of BBR. These findings indicate that BBR attenuates SNT-induced cardiac dysfunction by normalizing the calcium regulation disorder via SGK1 activation.
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Berberina , Cardiopatías , Ratas , Ratones , Humanos , Animales , Sunitinib/metabolismo , Sunitinib/farmacología , Calcio/metabolismo , Berberina/farmacología , Cardiotoxicidad/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Cardiopatías/inducido químicamente , Cardiopatías/prevención & control , Cardiopatías/metabolismo , Miocitos CardíacosRESUMEN
Alternative splicing is an important step in eukaryotic mRNA pre-processing which increases the complexity of gene expression programs, but is frequently altered in disease. Previous work on the regulation of alternative splicing has demonstrated that splicing is controlled by RNA-binding proteins (RBPs) and by epigenetic DNA/histone modifications which affect splicing by changing the speed of polymerase-mediated pre-mRNA transcription. The interplay of these different layers of splicing regulation is poorly understood. In this paper, we derived mathematical models describing how splicing decisions in a three-exon gene are made by combinatorial spliceosome binding to splice sites during ongoing transcription. We additionally take into account the effect of a regulatory RBP and find that the RBP binding position within the sequence is a key determinant of how RNA polymerase velocity affects splicing. Based on these results, we explain paradoxical observations in the experimental literature and further derive rules explaining why the same RBP can act as inhibitor or activator of cassette exon inclusion depending on its binding position. Finally, we derive a stochastic description of co-transcriptional splicing regulation at the single-cell level and show that splicing outcomes show little noise and follow a binomial distribution despite complex regulation by a multitude of factors. Taken together, our simulations demonstrate the robustness of splicing outcomes and reveal that quantitative insights into kinetic competition of co-transcriptional events are required to fully understand this important mechanism of gene expression diversity.
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Empalme Alternativo , Empalme del ARN , Empalme del ARN/genética , Empalme Alternativo/genética , Proteínas de Unión al ARN/genética , Proteínas de Unión al ARN/metabolismo , Transcripción Genética , Sitios de UniónRESUMEN
A marked elevation of TLR4 was observed in various organs of septic mice. The mechanism of TLR4 in intestinal epithelial cell damage in sepsis remains unclear. CLP mice models were used to assess the role of TLR4 in intestinal Paneth cell damage by histological, polymerase chain reaction, western-blot analyses. The ileal expression of TLR4 was increased by more than five-fold after CLP. CLP significantly increased 7-day mortality and was associated with a higher murine sepsis score (MSS), closely related with increased TLR4 expression. Histological staining revealed that a reduced number of Paneth cells, accompanied by reduced lysozyme and defensin alpha 5(DEF-5) expression as detected by PCR. Of note, the expression levels of ATF6, XBP1 and CHOP increased in the ileal of the sepsis group. Meanwhile, the uncleaved p90 ATF6 was markedly reduced and cleaved p50 ATF6 was increased in the sepsis group. Intriguingly, The TAK-242 had improved intestinal mucosal injury, reduced the expression of ATF6, XBP1 and CHOP and relieved the cleavage of ATF6. We found that increased the expression level of TLR4 in the ileal of CLP mice promoted the depletion of Paneth cell and reduced LYZ and DEF-5 expression. Furthermore, our findings suggested that TLR4-mediated the hyperactivation of ER stress, via activating the ATF6/CHOP pathway, might be one of the mechanisms associated with Paneth cells loss and dysfunction during intestinal barrier impairment of sepsis.
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Células de Paneth , Sepsis , Animales , Estrés del Retículo Endoplásmico , Intestinos/patología , Ratones , Células de Paneth/metabolismo , Sepsis/metabolismo , Receptor Toll-Like 4/genética , Receptor Toll-Like 4/metabolismoRESUMEN
Hematopoietic stem cells (HSCs) produce highly diverse cell lineages. Here, we chart native lineage pathways emanating from HSCs and define their physiological regulation by computationally integrating experimental approaches for fate mapping, mitotic tracking, and single-cell RNA sequencing. We find that lineages begin to split when cells leave the tip HSC population, marked by high Sca-1 and CD201 expression. Downstream, HSCs either retain high Sca-1 expression and the ability to generate lymphocytes, or irreversibly reduce Sca-1 level and enter into erythro-myelopoiesis or thrombopoiesis. Thrombopoiesis is the sum of two pathways that make comparable contributions in steady state, a long route via multipotent progenitors and CD48hi megakaryocyte progenitors (MkPs), and a short route from HSCs to developmentally distinct CD48-/lo MkPs. Enhanced thrombopoietin signaling differentially accelerates the short pathway, enabling a rapid response to increasing demand. In sum, we provide a blueprint for mapping physiological differentiation fluxes from HSCs and decipher two functionally distinct pathways of native thrombopoiesis.
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Células Madre Hematopoyéticas , Trombopoyesis , Diferenciación Celular/fisiología , Linaje de la Célula , Células Madre Hematopoyéticas/metabolismo , Mielopoyesis , Trombopoyesis/fisiologíaRESUMEN
Eukaryotic circadian clocks are based on self-sustaining, cell-autonomous oscillatory feedback loops that can synchronize with the environment via recurrent stimuli (zeitgebers) such as light. The components of biological clocks and their network interactions are becoming increasingly known, calling for a quantitative understanding of their role for clock function. However, the development of data-driven mathematical clock models has remained limited by the lack of sufficiently accurate data. Here we present a comprehensive model of the circadian clock of Neurospora crassa that describe free-running oscillations in constant darkness and entrainment in light-dark cycles. To parameterize the model, we measured high-resolution time courses of luciferase reporters of morning and evening specific clock genes in WT and a mutant strain. Fitting the model to such comprehensive data allowed estimating parameters governing circadian phase, period length and amplitude, and the response of genes to light cues. Our model suggests that functional maturation of the core clock protein Frequency causes a delay in negative feedback that is critical for generating circadian rhythms.
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Relojes Circadianos , Neurospora crassa , Relojes Circadianos/genética , Ritmo Circadiano/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Neurospora crassa/genéticaRESUMEN
Cardiotoxicity by tyrosine kinase inhibitors remains an important concern. Nilotinib and vandetanib clinically carry high proarrhythmic risk and the exact mechanism underlying arrhythmogenesis is not fully understood. In this study, we investigated the effects of nilotinib and vandetanib on the abundance of human ether-á-go-go-related gene (hERG) K+ channel and assessed the potential role of acute hERG blockage versus chronic effects in arrhythmogenesis. We found that both nilotinib and vandetanib prolonged the field potential duration reflecting the repolarisation process and induced cellrythmias of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) in a time-and concentration-dependent manner after, after chronic exposure. Patch-clamp recordings revealed significant reductions of hERG current densities by nilotinib or vandetanib after chronic incubation with hERG-HEK293 cells in addition to the acute inhibition. Western blot analysis showed that nilotinib and vandetanib decreased mature hERG protein (155-kDa) expression, in a greater extent than that of the immature form (135-kDa). A serum and glucocorticoid kinase 1 (SGK1) activator, C4-ceramide, prevented the nilotinib-and vandetanib-induced hERG protein downregulation and thus the incidence of cellrrhythmias. Taken together, our data demonstrated that the downregulation of hERG channel abundance on the cellular membrane predominantly contributed to the proarrhythmic effect of nilotinib and vandetanib.
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Canales de Potasio Éter-A-Go-Go , Células Madre Pluripotentes Inducidas , Arritmias Cardíacas/inducido químicamente , Arritmias Cardíacas/metabolismo , Regulación hacia Abajo , Canal de Potasio ERG1/metabolismo , Canales de Potasio Éter-A-Go-Go/genética , Canales de Potasio Éter-A-Go-Go/metabolismo , Células HEK293 , Humanos , Miocitos Cardíacos , Piperidinas , Inhibidores de Proteínas Quinasas/toxicidad , Pirimidinas , QuinazolinasRESUMEN
With the rapid development of industrialization and urbanization in China, the ecological environment has been damaged, especially the air quality, which has negatively impacted the productivity and lives of residents. China has taken various measures to improve air quality, and industrial upgrading is one of these measures. This article uses urban and provincial data from 2015 to 2018 and a multilevel growth model to study how industrial upgrading can improve air quality. The following conclusions are drawn through empirical analysis. If industrial upgrading is not considered, with time, air quality will gradually deteriorate. However, once the country adopts strategic measures for industrial upgrading, the combined effect of industrial upgrading and time will improve air quality. Industrial upgrading and industrial restructuring jointly reduce air pollution and have a significant impact on the improvement of air quality. Company goals for economic profit and survival will eventually lead to overall industrial upgrades that have little effect on air improvement. According to the empirical results, this paper puts forward some suggestions to improve the air quality.
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Contaminación del Aire , Contaminación del Aire/análisis , China , Desarrollo Económico , Eficiencia , Desarrollo Industrial , Industrias , UrbanizaciónRESUMEN
The effect of targeted therapy for metastatic hepatocellular carcinoma (HCC) is still unsatisfactory. Exploring the underlying mechanism of HCC metastasis is favorable to provide new therapeutic strategies. T-box (TBX) transcription factor family genes, which are crucial regulators in embryo and organ development, are vital for regulating tumor initiation, growth and metastasis. Here we explored the role of TBX19 in HCC metastasis, which is one of the most upregulated TBX family genes in human HCC tissues. TBX19 expression was markedly upregulated in HCC tissues and elevated TBX19 expression predicted poor prognosis. Overexpression of TBX19 enhanced HCC metastasis through upregulating epidermal growth factor receptor (EGFR) and Rac family small GTPase 1 (RAC1) expression. Downregulation of EGFR and RAC1 inhibited TBX19-mediated HCC metastasis, while upregulation of EGFR and RAC1 restored inhibition of HCC metastasis mediated by TBX19 knockdown. Furthermore, epidermal growth factor (EGF)/EGFR signaling upregulated TBX19 expression via the extracellular signal-regulated kinase (ERK)/nuclear factor (NF)-kB axis. Besides, the combined application of EGFR inhibitor Erlotinib and RAC1 inhibitor NSC23766 markedly inhibited TBX19-mediated HCC metastasis. In HCC cohorts, TBX19 expression was positively associated with EGFR and RAC1 expression. Patients with positive coexpression of TBX19/EGFR or TBX19/RAC1 displayed the poorest prognosis. In conclusion, EGF/EGFR signaling upregulated TBX19 expression via ERK/NF-kB pathway and TBX19 fostered HCC metastasis by enhancing EGFR and RAC1 expression, which formed an EGF-TBX19-EGFR positive feedback loop. Targeting this signaling pathway may offer a potential therapeutic strategy to efficiently restrain TBX19-mediated HCC metastasis.
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Carcinoma Hepatocelular , Receptores ErbB , Neoplasias Hepáticas , Proteína de Unión al GTP rac1 , Carcinoma Hepatocelular/patología , Línea Celular Tumoral , Factor de Crecimiento Epidérmico/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/genética , Proteínas de Homeodominio/metabolismo , Humanos , Neoplasias Hepáticas/patología , Metástasis de la Neoplasia , Proteínas de Dominio T Box/genética , Proteínas de Dominio T Box/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteína de Unión al GTP rac1/genética , Proteína de Unión al GTP rac1/metabolismoRESUMEN
The average annual growth rate of China's waste emissions from 2007 to 2017 was 2.3%. The main pollutants in the wastewater are chemical oxygen demand, ammonia nitrogen, total ammonia, total phosphorus, and so on which pollute groundwater and destroy ecosystems. Poor water quality reduces the edible value of agricultural products and has an impact on human health. Based on the panel data of 31 provinces in China from 2007 to 2017, this paper uses a dynamic spatial panel lag model to study the impact of China's water pollution on agricultural economic growth. The results show that the impact of China's water pollution on agricultural economic growth is significant. If the intensity of wastewater discharge is taken as an input factor in the process of agricultural production, the growth of agricultural economy tends to decline with the increase of water pollution. In the effect analysis, the short-term and long-term effects are significant. The absolute value of the long-term total effect is far greater than the short-term total effect, indicating that the inhibitory effect of water pollution on agricultural economic growth is more obvious. The cumulative effect of water pollution on agricultural economic growth continues to expand, resulting in more and more economic losses. The central and local governments should take various measures to reduce water pollution, guide the green development of agriculture, and increase farmers' income to realize the rural revitalization plan.
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Desarrollo Económico , Ecosistema , Agricultura , China , Humanos , Contaminación del AguaRESUMEN
Haze pollution in China is very serious and has become the source of mortality, affecting the health and lives of residents. The Chinese government adopts different policy measures to reduce haze pollution. The impact of different types of environmental regulations on haze pollution has become a hot topic for academics and government departments. Based on panel data from 2005-2017, this paper studies the effect of different types of environmental regulations on haze pollution in 30 provinces of China using a panel quantile model. The results show that when haze pollution changes from a low quantile to a high quantile, the marginal impact of command-and-control environmental regulation on haze pollution changes from 0.122 to -0.332. Command-and-control environmental regulation can reduce haze pollution, but its impact is not significant. The main reason for this finding is that environmental law enforcement is not strict. The marginal impact of economically restrained environmental regulation on haze pollution changes from -14.389 to 49.939. Economically restrained environmental regulation can reduce haze pollution in low quantiles, but not in high quantiles. The collection of sewage charges fees is far less than the total profit, which has no deterrent effect on enterprises. The marginal impact of public participation in environmental regulation on haze pollution changes from 0.154 to -0.002. Public participation in environmental regulation cannot reduce haze pollution in low quantiles, but can in high quantiles; however its impact becomes insignificant. This study reveals the quantile-based discrepancy in the effect of environmental regulation on haze pollution, and offers a new perspective for research on the effects of environmental regulation.
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Contaminación del Aire/análisis , Investigación Empírica , Control Social Formal , China , Análisis de RegresiónRESUMEN
Using the panel data of China's provinces from 2005 to 2016, the paper adopts the ultra-efficiency model to measure the green economy efficiency of each province. Then, the paper used the panel threshold model to study the impact of science and technological input on the green economy efficiency with the energy consumption intensity as a threshold variable. The results show that the green economy efficiency in China's provinces is low and is in a downward trend. When the energy consumption intensity is the threshold variable, the single-threshold effect is significant. When the energy consumption intensity is lower than the threshold value, the impact of science and technological input on green economic efficiency is not significant, and the energy consumption intensity has a significant impact on green economic efficiency with science and technological input and energy consumption intensity as the core explanatory variables and with energy consumption intensity as the threshold variable. When the energy consumption intensity crosses the threshold value, the impact of science and technological input and energy consumption intensity on green economic efficiency becomes significant. According to the above empirical results, this paper proposes corresponding countermeasures and suggestions.
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Industrias , Tecnología , China , Eficiencia , Investigación EmpíricaRESUMEN
We report the synergistic adsorption and activation of CO2 by using magnesium oxide anchored into a hollow carbon sphere (MgO/HCS) as an efficient catalyst for electrochemical reduction of CO2 (ERC). The MgO/HCS catalyst exhibits a high selectivity for CO production with a faradaic efficiency of 81.7% at -1.0 V vs. RHE and a partial current density (PCD) of 16.7 mA cm-2 in aqueous electrolyte.
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The critical bottleneck of electrocatalytic CO2 reduction reaction (CO2RR) lies in its low efficiency at high overpotential caused by competitive hydrogen evolution. It is challenging to develop an efficient catalyst achieving both high current density and high Faradaic efficiency (FE) for CO2RR. Herein, we synthesized fluorine-doped cagelike porous carbon (F-CPC) by purposely tailoring its structural properties. The optimized F-CPC possesses large surface area with moderate mesopore and abundant micropores as well as high electrical conductivity. When used as catalyst for CO2RR, F-CPC exhibits FE of 88.3% for CO at -1.0 V vs RHE with a current density of 37.5 mA·cm -2. Experimental results and finite element simulations demonstrate that the excellent CO2RR performance of F-CPC at high overpotential should be attributed to its structure-enhanced electrocatalytic process stemming from its cagelike morphology.
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Startup-shutdown cycling is one of the main factors that contribute to fuel cell deterioration related to high cathode potential. In this study, a coupled model with the carbon corrosion model and agglomerate model of the cathode catalyst layer is built to predict performance degradation during startup-shutdown cycles. The carbon corrosion model calculates the carbon loading loss through the rate equations and material balance expressions of seven reactions, while the agglomerate model describes the catalyst layer performance according to the computed structural parameters. A set of operational and structural parametric studies are used to investigate their effects on initial performance and voltage degradation rate. The maximum voltage of the cyclic load is found to have a greater influence over the voltage degradation rate compared with relative humidity, pressure, and minimum voltage of the cyclic load. Among the structural parameters, the carbon loading and platinum loading have the greatest and least impact on voltage degradation rate, respectively, while ionomer fraction has a complex and nonmonotonic effect. An optimal design strategy is provided with a case demonstration. Results may provide a fundamental and important tool for degradation prediction in startup-shutdown conditions and guidance for catalyst layer design and operation.