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Recurrent events, including cardiovascular events, are commonly observed in biomedical studies. Understanding the effects of various treatments on recurrent events and investigating the underlying mediation mechanisms by which treatments may reduce the frequency of recurrent events are crucial tasks for researchers. Although causal inference methods for recurrent event data have been proposed, they cannot be used to assess mediation. This study proposed a novel methodology of causal mediation analysis that accommodates recurrent outcomes of interest in a given individual. A formal definition of causal estimands (direct and indirect effects) within a counterfactual framework is given, and empirical expressions for these effects are identified. To estimate these effects, a semiparametric estimator with triple robustness against model misspecification was developed. The proposed methodology was demonstrated in a real-world application. The method was applied to measure the effects of two diabetes drugs on the recurrence of cardiovascular disease and to examine the mediating role of kidney function in this process.
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Enfermedades Cardiovasculares , Causalidad , Análisis de Mediación , Modelos Estadísticos , Recurrencia , Humanos , Simulación por Computador , Interpretación Estadística de Datos , Hipoglucemiantes/uso terapéuticoRESUMEN
Radiotherapy is an effective therapy in tumour treatment. However, the characteristics of the tumour microenvironment, including hypoxia, low pH, and interstitial fluid pressure bring about radioresistance. To improve the anti-tumour effect of radiotherapy, it has been demonstrated that antiangiogenic therapy can be employed to repair the structural and functional defects of tumour angiogenic vessels, thereby preventing radioresistance or poor therapeutic drug delivery. In this study, we prepared triptolide (TP)-loaded Asn-Gly-Arg (NGR) peptide conjugated mPEG2000-DSPE-targeted liposomes (NGR-PEG-TP-LPs) to induce tumour blood vessel normalisation, to the end of increasing the sensitivity of tumour cells to radiotherapy. Further, to quantify the tumour vessel normalisation window, the structure and functionality of tumour blood vessels post NGR-PEG-TP-LPs treatment were evaluated. Thereafter, the anti-tumour effect of radiotherapy following these treatments was evaluated using HCT116 xenograft-bearing mouse models based on the tumour vessel normalisation period window. The results obtained showed that NGR-PEG-TP-LPs could modulate tumour vascular normalisation to increase the oxygen content of the tumour microenvironment and enhance the efficacy of radiotherapy. Further, liver and kidney toxicity tests indicated that NGR-PEG-TP-LPs are safe for application in cancer treatment.
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Diterpenos , Neoplasias , Humanos , Ratones , Animales , Liposomas/química , Lipopolisacáridos , Sistemas de Liberación de Medicamentos/métodos , Diterpenos/química , Línea Celular TumoralRESUMEN
Growing evidence indicates that circulating lactoferrin (Lf) is implicated in peripheral cholesterol metabolism disorders. It has emerged that the distribution of Lf changes in astrocytes of aging brains and those exhibiting neurodegeneration; however, its physiological and/or pathological role remains unknown. Here, we demonstrate that astrocyte-specific knockout of Lf (designated cKO) led to decreased body weight and cognitive abnormalities during early life in mice. Accordingly, there was a reduction in neuronal outgrowth and synaptic structure in cKO mice. Importantly, Lf deficiency in the primary astrocytes led to decreased sterol regulatory element binding protein 2 (Srebp2) activation and cholesterol production, and cholesterol content in cKO mice and/or in astrocytes was restored by exogenous Lf or a Srebp2 agonist. Moreover, neuronal dendritic complexity and total dendritic length were decreased after culture with the culture medium of the primary astrocytes derived from cKO mice and that this decrease was reversed after cholesterol supplementation. Alternatively, these alterations were associated with an activation of AMP-activated protein kinase (AMPK) and inhibition of SREBP2 nuclear translocation. These data suggest that astrocytic Lf might directly or indirectly control in situ cholesterol synthesis, which may be implicated in neurodevelopment and several neurological diseases.
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Astrocitos , Proteína 2 de Unión a Elementos Reguladores de Esteroles , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Astrocitos/metabolismo , Colesterol/metabolismo , Lactoferrina/genética , Lactoferrina/metabolismo , Lactoferrina/farmacología , Ratones , Proteína 2 de Unión a Elementos Reguladores de Esteroles/genética , Proteína 2 de Unión a Elementos Reguladores de Esteroles/metabolismoRESUMEN
PURPOSE: COVID-19 is also referred to as a typical viral septic pulmonary infection by 2019-nCoV. However, little is known regarding its characteristics in terms of systemic inflammation and organ injury, especially compared with classical bacterial sepsis. This article aims to investigate the clinical characteristics and prognosis between COVID-19-associated sepsis and classic bacterial-induced sepsis. METHODS: In this retrospective cohort study, septic patients with COVID-19 in the intensive care unit (ICU) of a government-designed therapy center in Shenzhen, China between January 14, 2020 and March 10, 2020, and septic patients induced by carbapenem-resistant klebsiella pneumonia (CrKP) admitted to the ICU of the Second People's Hospital of Shenzhen, China between January 1, 2014 and October 30, 2019 were enrolled. Demographic and clinical parameters including comorbidities, critical illness scores, treatment, and laboratory data, as well as prognosis were compared between the two groups. Risk factors for mortality and survival rate were analyzed using multivariable logistic regression and survival curve, respectively. RESULTS: A total of 107 patients with COVID-19 and 63 patients with CrKP were enrolled. A direct comparison between the two groups demonstrated more serious degrees of primary lung injury following 2019-nCoV infection (indicated by lower PaO2/FiO2), but milder systemic inflammatory response, lower sequential organ failure assessment score and better functions of the organs like heart, liver, kidney, coagulation, and circulation. However, the acquired immunosuppression presented in COVID-19 patients was more severe, which presented as lower lymphocyte counts (0.8×109/L vs. 0.9×109/L). Moreover, the proportion of COVID-19 patients treated with corticosteroid therapy and extracorporeal membrane oxygenation was larger compared with CrKP patients (78.5% vs. 38.1% and 6.5% vs. 0, respectively) who required less invasive mechanical ventilation (31.6% vs. 54.0%). The incidence of hospitalized mortality and length of ICU stay and total hospital stay were also lower or shorter in viral sepsis (12.1% vs. 39.7%, 6.5 days vs. 23.0 days and 21.0 days vs. 33.0 days, respectively) (all p < 0.001). Similar results were obtained after being adjusted by age, gender, comorbidity and PaO2/FiO2. Lymphocytopenia and high acute physiology and chronic health evaluation II scores were common risk factors for in-hospital death. While the death cases of COVID-19 sepsis mostly occurred at the later stages of patients' hospital stay. CONCLUSION: Critical COVID-19 shares clinical characteristics with classical bacterial sepsis, but the degree of systemic inflammatory response, secondary organ damage and mortality rate are less severe. However, following 2019-nCoV infection, the level of immunosuppression may be increased and thus induce in more death at the later stage of patients' hospitalstay.
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COVID-19 , Sepsis , Carbapenémicos , Mortalidad Hospitalaria , Humanos , Unidades de Cuidados Intensivos , Klebsiella , Pronóstico , Estudios Retrospectivos , SARS-CoV-2RESUMEN
OBJECTIVE: The objective of this study was to assess the relationship between serum procalcitonin (PCT) and acute kidney injury (AKI) induced by bacterial septic shock. METHODS: A retrospective study was designed which included patients who were admitted to the ICU from January 2015 to October 2018. Multiple logistic regression and receiver operating characteristic (ROC) as well as smooth curve fitting analysis were used to assess the relationship between the PCT level and AKI. RESULTS: Of the 1,631 patients screened, 157 patients were included in the primary analysis in which 84 (53.5%) patients were with AKI. Multiple logistic regression results showed that PCT (odds ratio [OR] = 1.017, 95% confidence interval [CI] 1.009-1.025, p < 0.001) was associated with AKI induced by septic shock. The ROC analysis showed that the cutoff point for PCT to predict AKI development was 14 ng/mL, with a sensitivity of 63% and specificity 67%. Specifically, in multivariate piecewise linear regression, the occurrence of AKI decreased with the elevation of PCT when PCT was between 25 ng/mL and 120 ng/mL (OR 0.963, 95% CI 0.929-0.999; p = 0.042). The AKI increased with the elevation of PCT when PCT was either <25 ng/mL (OR 1.077, 95% CI 1.022-1.136; p = 0.006) or >120 ng/mL (OR 1.042, 95% CI 1.009-1.076; p = 0.013). Moreover, the PCT level was significantly higher in the AKI group only in female patients aged ≤75 years (p = 0.001). CONCLUSIONS: Our data revealed a nonlinear relationship between PCT and AKI in septic shock patients, and PCT could be used as a potential biomarker of AKI in female patients younger than 75 years with bacterial septic shock.
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Lesión Renal Aguda/sangre , Polipéptido alfa Relacionado con Calcitonina/sangre , Choque Séptico/sangre , Lesión Renal Aguda/etiología , Anciano , Infecciones Bacterianas/sangre , Infecciones Bacterianas/complicaciones , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Choque Séptico/complicacionesRESUMEN
Gliomas are the most common form of malignant tumour in the central nervous system. However, the molecular mechanism of the tumorigenesis and progression of gliomas remains unclear. In this study, we used the GEO database to identify genes differentially expressed in gliomas and predict the prognosis of glioma. We observed that ASPM mRNA was increased obviously in glioma tissue, and higher ASPM mRNA expression predicted worse disease prognosis. ASPM was highly expressed in glioma cell lines U87-MG and U251, and knockdown of ASPM expression in these cells significantly repressed the proliferation, migration and invasion ability and induced G0/G1 phase arrest. In addition, down-regulation of ASPM suppressed the growth of glioma in nude mice. Five potential binding sites for transcription factor FoxM1 were predicted in the ASPM promoter. FoxM1 overexpression significantly increased the expression of ASPM and promoted the proliferation and migration of glioma cells, which was abolished by ASPM ablation. ChIP and dual-luciferase reporter analysis confirmed that FoxM1 bound to the ASPM promoter at -236 to -230 bp and -1354 to -1348 bp and activated the transcription of ASPM directly. Collectively, our results demonstrated for the first time that aberrant ASPM expression mediated by transcriptional regulation of FoxM1 promotes the malignant properties of glioma cells.
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Proteína Forkhead Box M1/genética , Glioma/genética , Proteínas del Tejido Nervioso/genética , Transcripción Genética/genética , Animales , Carcinogénesis/genética , Carcinogénesis/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Regulación hacia Abajo/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Glioma/patología , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Pronóstico , Regiones Promotoras Genéticas/genéticaRESUMEN
A series of 6-aminocarbonyl pyrrolo[2,1-f][1,2,4]triazine derivatives were designed by scaffold hopping strategy. The IC50 values of compound 14a against PI3Ks were measured, showing selective activity against p110α and p110δ with IC50s of 122 nM and 119 nM respectively. All the synthesized compounds were evaluated for their antiproliferative activity against human cancer cells by SRB assay. Compounds 14a, 14p and 14q exhibited potent antiproliferative activity against five types of human cancer cells and the PK property of 14q was also investigated here.
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Antineoplásicos/farmacología , Diseño de Fármacos , Inhibidores de Proteínas Quinasas/farmacología , Triazinas/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Estructura Molecular , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Relación Estructura-Actividad , Triazinas/síntesis química , Triazinas/químicaRESUMEN
The aim of this study was to investigate the association between nadir platelet count and acute kidney injury (AKI) or 28-day all-cause mortality induced by hemorrhagic shock (HS), and to determine the cutoff value of nadir platelet count in HS clinical practice. This retrospective study included hospitalized patients enrolled in a tertiary-care teaching hospital from January 1, 2010 to December 31, 2015. Clinical data from HS admitted to the intensive care unit (ICU) were evaluated. Nadir platelet count was defined as the lowest values in the first 48 h. Multivariate logistic regression and Cox proportional hazards regression were used to assess the correlation between nadir platelet count and AKI or 28-day all-cause mortality induced by HS, respectively; the area under receiver operating characteristic (AU-ROC) and Youde's index were used to determine the optimal cutoff value of nadir platelet count. Kaplan-Meier's method and log-rank test were assessed for the 28-day all-cause mortality in AKI and non-AKI groups. Of 1589 patients screened, 84 patients (mean age,37.1 years; 58 males) were included in the primary analysis in which 30 patients with AKI. Multiple logistic results indicated that nadir platelet count was a risk factor of AKI (OR = 0.71,95% confidence interval [CI] 0.54-0.93, P < 0.05). Cox regression analysis revealed that nadir platelet count was independent risk factors for 28-day all-cause mortality (Hazard ratios [HR]0.89,95%CI 0.76-0.99, P < 0.05). Kaplan-Meier curve showed that 28-day all-cause mortality was significantly higher in patients with AKI than non-AKI (P < 0.001).These results suggest that nadir platelet count in the first 48 h is a new biomarker for AKI and 28-day all-cause mortality induced by HS. Moreover, the risk for AKI and 28-day all-cause mortality in HS patients decreased by 29% and 11%, respectively, for every 10 × 109/L increase in platelet count. Additional studies are needed to investigate whether elevation of nadir platelet count reduces the risk in different genders.
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Lesión Renal Aguda/sangre , Lesión Renal Aguda/etiología , Biomarcadores , Recuento de Plaquetas , Choque Hemorrágico/complicaciones , Lesión Renal Aguda/diagnóstico , Lesión Renal Aguda/mortalidad , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Transfusión Sanguínea , Causas de Muerte , Femenino , Humanos , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Pronóstico , Modelos de Riesgos Proporcionales , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Choque Hemorrágico/etiología , Choque Hemorrágico/mortalidad , Choque Hemorrágico/terapia , Adulto JovenRESUMEN
BACKGROUND AND OBJECTIVES: To investigate the effect of accelerated rehabilitation combined with enteral nutrition on surgically treated lung cancer patients. METHODS AND STUDY DESIGN: In total, 150 lung cancer patients treated in our hospital from January 2017 to January 2018 were retrospectively analysed. Sixty-six patients were randomly divided into a control group with conventional nutrition (Con group) and an accelerated rehabilitation combined with enteral nutrition group (EN group). Postoperative drainage; total hospitalization time; total hospitalization expenses; and albumin, haemoglobin and total lymphocyte counts (TLC) before and after treatment were compared. RESULTS: The serum albumin, prealbumin and haemoglobin in both groups were decreased after operation and were significantly higher in the EN group (p<0.05) than in the Con group. The TLC decreased in both groups after operation and were significantly higher in the EN group than in the con group. The postoperative drainage volume, total hospitalization time and total hospitalization expenses were significantly lower in the EN group than in the Con group (p<0.05). CONCLUSIONS: The effect of accelerated rehabilitation combined with enteral nutrition in lung cancer surgery patients is clear. Surgery leads to stress, which enhances catabolism and reduces the synthesis of carbohydrates, protein, and fat, increasing patients' nutritional risk. Nutritional support combined with fast-track minimally invasive thoracic surgery for at-risk lung cancer patients who undergo preoperative nutritional screening and assessment can reduce postoperative complications and hospitalization time and improve nutritional indicators, immunity, respiratory function recovery and clinical outcomes, leading to socioeconomic benefits.
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Nutrición Enteral , Neoplasias Pulmonares/cirugía , Desnutrición/prevención & control , Femenino , Humanos , Neoplasias Pulmonares/rehabilitación , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/prevención & control , Estudios RetrospectivosRESUMEN
With both spin and valley degrees of freedom, the low-lying excitonic spectra of photoexcited transition-metal dichalcogenide monolayers (TMDC-MLs) are featured by rich fine structures, comprising the intravalley bright exciton states as well as various intra- and intervalley dark ones. The latter states can be classified as those of the spin- and momentum-forbidden dark excitons according to the violated optical selection rules. Because of their optical invisibility, these two types of the dark states are in principle hardly observed and even distinguished in conventional spectroscopies although their impacts on the optical and dynamical properties of TMDC-MLs have been well noticed. In this Letter, we present a theoretical and computational investigation of the exciton fine structures and the temperature-dependent photoluminescence spectra of strained tungsten diselenide monolayers (WSe2-MLs) where the intravalley spin-forbidden dark exciton lies in the lowest exciton states and other momentum-forbidden states are in the higher energies that are tunable by external stress. The numerical computations are carried out by solving the Bethe-Salpeter equation for an exciton in a WSe2-ML under the stress-control in the tight-binding scheme established from the first principle computation in the density functional theory. According to the numerical computation and supportive model analysis, we reveal the distinctive signatures of the spin- and momentum-forbidden exciton states of strained WSe2-MLs in the temperature-dependent photoluminescences and present the guiding principle to infer the relative energetic locations of the two types of dark excitons.
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BACKGROUND/AIMS: In the current study, we performed an integrated analysis of genome-wide methylation and gene expression data to find novel prognostic genes for lower-grade gliomas (LGGs). METHODS: First, TCGA methylation data were used to identify prognostic genes associated with promoter methylation. Second, candidate genes that were stably regulated by promoter methylation were explored. Third, Cox proportional hazards regression analysis was used to generate a prognostic signature, and the signature genes were used to construct a survival risk score system. RESULTS: Three genes (EMP3, GSX2 and EMILIN3) were selected as signature genes. These three signature genes were used to construct a survival risk score system. The high-risk group exhibited significantly worse overall survival (OS) and relapse-free survival (RFS) as compared to the low-risk group in the TCGA dataset. The association of the three-gene prognostic signature with patient' survival was then validated using the CGGA dataset. Moreover, Kaplan-Meier plots showed that the three-gene prognostic signature risk remarkably stratified grade II and grade III patients in terms of both OS and RFS in the TCGA cohort. There was also a significant difference between the low- and high-risk groups in IDH wild-type glioma patients, indicating that the three-gene signature may be able to help in predicting prognosis for patients with IDH wild-type gliomas. CONCLUSION: We identified and validated a three-gene (EMP3, GSX2 and EMILIN3) prognostic signature in LGGs by integrating multidimensional genomic data from the TCGA and CGGA datasets, which may help in fine-tuning the current histology-based tumors classification system and providing better stratification for future clinical trials.
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Antígenos de Superficie/genética , Neoplasias del Sistema Nervioso Central/genética , Metilación de ADN , Glioma/genética , Proteínas de Homeodominio/genética , Glicoproteínas de Membrana/genética , Adulto , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Glioma/diagnóstico , Glioma/patología , Humanos , Estimación de Kaplan-Meier , Masculino , Recurrencia Local de Neoplasia/genética , Pronóstico , Regiones Promotoras Genéticas , TranscriptomaRESUMEN
The study aimed to develop a real-time electromyography (EMG) signal acquiring and processing device that can acquire signal during electrical stimulation. Since electrical stimulation output can affect EMG signal acquisition, to integrate the two elements into one system, EMG signal transmitting and processing method has to be modified. The whole system was designed in a user-friendly and flexible manner. For EMG signal processing, the system applied Altera Field Programmable Gate Array (FPGA) as the core to instantly process real-time hybrid EMG signal and output the isolated signal in a highly efficient way. The system used the power spectral density to evaluate the accuracy of signal processing, and the cross correlation showed that the delay of real-time processing was only 250 µs.
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Terapia por Estimulación Eléctrica/instrumentación , Electromiografía/métodos , Procesamiento de Señales Asistido por Computador/instrumentación , Humanos , Diseño de Software , Factores de TiempoRESUMEN
In China, many surveys have shown that most people do not have a correct understanding about cold and administration of anti-cold Chinese patent medicine preparations. The author conducted a systematic summary and analysis on the actual application of anti-cold Chinese patent medicine preparations as well as the warning on safe application of anti-cold Chinese patent medicine preparations in Clinical Medication Information of China Pharmacopoeia, in the expectation of reducing the blind application of anti-cold Chinese patent medicine preparations and providing traditional Chinese medicine pharmacists new ideas in monitoring the safe application of exterior syndrome-relieving Chinese patent medicine preparations.
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Resfriado Común/tratamiento farmacológico , Medicamentos Herbarios Chinos/efectos adversos , China , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Medicamentos sin Prescripción/efectos adversos , Medicamentos sin Prescripción/química , Medicamentos sin Prescripción/uso terapéuticoRESUMEN
In this paper, we explore the challenges associated with biomarker identification for diagnosis purpose in biomedical experiments, and propose a novel approach to handle the above challenging scenario via the generalization of the Dantzig selector. To improve the efficiency of the regularization method, we introduce a transformation from an inherent nonlinear programming due to its nonlinear link function into a linear programming framework under a reasonable assumption on the logistic probability range. We illustrate the use of our method on an experiment with binary response, showing superior performance on biomarker identification studies when compared to their conventional analysis. Our proposed method does not merely serve as a variable/biomarker selection tool, its ranking of variable importance provides valuable reference information for practitioners to reach informed decisions regarding the prioritization of factors for further investigations.
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Biomarcadores , ProbabilidadRESUMEN
Chemical weathering is a pivotal geochemical process that shapes the carbon cycling and climates in the critical zone. Among its critical drivers, river discharge holds a particular significance, especially in the orogenic landscapes. Here, we examined the impact of discharge on mineral weathering in southwestern (SW) Taiwan by analyzing river water chemistry across a wide discharge range. Current observations indicated that carbonate contributes significantly to total weathering (50-80 %), with sulfuric acid accounting for one-half to two-thirds of carbonate weathering. A statistically strong correlation between river discharge and sulfuric acid-mediated carbonate weathering was highlighted, while the silicate weathering remained constant. This relationship suggests an increased influx of fresh minerals, such as pyrite, into the weathering regime as water flow increases. Our model identifies a critical discharge threshold of 4.6 m3 s-1, determining whether mineral weathering acts as a net source or sink of CO2. Consequently, mineral weathering in SW Taiwan acts as a net CO2 sink during dry periods but turns into a net source during wet periods. Through analyzing a decade of daily discharge data, we found mineral weathering in SW Taiwan is a net CO2 source, with a 2.6-fold increase in annual mean discharge causing a 3.8-fold increase in net CO2 flux. This pattern is likely to be applicable to other similar minerals containing mountain-building regions, highlighting the significant role of hydrology in determining weathering sources and their potential impact on the carbon cycle balance.
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Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune-mediated primary inflammatory myelinopathy of the central nervous system that primarily affects the optic nerve and spinal cord. The aquaporin 4 antibody (AQP4-Ab) is a specific autoantibody marker for NMOSD. Most patients with NMOSD are seropositive for AQP4-Ab, thus aiding physicians in identifying ways to treat NMOSD. AQP4-Ab has been tested in many clinical and laboratory studies, demonstrating effectiveness in diagnosing NMOSD. Recently, novel assays have been developed for the rapid and accurate detection of AQP4-Ab, providing further guidance for the diagnosis and treatment of NMOSD. This article summarizes the importance of rapid and accurate diagnosis for treating NMOSD based on a review of the latest relevant literature. We discussed current challenges and methods for improvement to offer new ideas for exploring rapid and accurate AQP4-Ab detection methods, aiming for early diagnosis of NMOSD.
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This paper quantifies the allocation of ecosystem services value (ESV) associated with land use pattern and qualitatively examined impacts of land use changes and socio-economic factors on spatiotemporal variation of ESV in the Natural Wetland Distribution Area (NWDA), Fuzhou city, China. The results showed that total ESV of the study area decreased from 4,332.16 × 10(6) RMB Yuan in 1989 to 3,697.42 × 10(6) RMB Yuan in 2009, mainly due to the remarkable decreases in cropland (decreased by 55.3 %) and wetland (decreased by 74.2 %). Forest, water, and wetland played major roles in providing ecosystem services, accounting for over 90 % of the total ESV. Based on time series Landsat TM/ETM+ imagery, geographic information system, and historical data, analysis of the spatiotemporal variation of ESV from 1989 to 2009 was performed. It indicated that rapid expansion of urban areas along the Minjiang River resulted in significant changes in land use types, leading to a dramatic decline in ecosystem services. Meanwhile, because of land scarcity and unique ecosystem functions, the emergency of wetland and cropland protection in built-up area has become an urgent task of local authorities to the local government. Furthermore, there was still a significant negative correlation between ESV of cropland and wetland and the GDP. The results suggest that future planning of land use pattern should control encroachment of urban areas into cropland and wetland in addition to scientific and rational policies towards minimizing the adverse effects of urbanization.
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Desarrollo Económico/estadística & datos numéricos , Monitoreo del Ambiente , Urbanización/tendencias , Humedales , Agricultura/estadística & datos numéricos , China , Ciudades/estadística & datos numéricos , Conservación de los Recursos Naturales , Sistemas de Información Geográfica , Tecnología de Sensores Remotos , Nave Espacial , Árboles/crecimiento & desarrolloRESUMEN
Parkinson's disease (PD) is one of the most widespread neurodegenerative diseases. PD is associated with progressive loss of substantia nigra dopaminergic neurons, including various motor symptoms (e.g., bradykinesia, rigidity, and resting tremor), as well as non-motor symptoms (e.g., cognitive impairment, constipation, fatigue, sleep disturbance, and depression). PD involves multiple biological processes, including mitochondrial or lysosomal dysfunction, oxidative stress, insulin resistance, and neuroinflammation. Metabolic syndrome (MetS), a collection of numerous connected cerebral cardiovascular conditions, is a common and growing public health problem associated with many chronic diseases worldwide. MetS components include central/abdominal obesity, systemic hypertension, diabetes, and atherogenic dyslipidemia. MetS and PD share multiple pathophysiological processes, including insulin resistance, oxidative stress, and chronic inflammation. In recent years, MetS has been linked to an increased risk of PD, according to studies; however, the specific mechanism remains unclear. Researchers also found that some related metabolic therapies are potential therapeutic strategies to prevent and improve PD. This article reviews the epidemiological relationship between components of MetS and the risk of PD and discusses the potentially relevant mechanisms and recent progress of MetS as a risk factor for PD. Furthermore, we conclude that MetS-related therapies are beneficial for the prevention and treatment of PD.
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Resistencia a la Insulina , Síndrome Metabólico , Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/epidemiología , Enfermedad de Parkinson/tratamiento farmacológico , Síndrome Metabólico/complicaciones , Síndrome Metabólico/epidemiología , Síndrome Metabólico/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Mitocondrias/metabolismoRESUMEN
Parkinson's disease (PD) is a common age-related neurodegenerative disorder characterized by damage to nigrostriatal dopaminergic neurons. Key pathogenic mechanisms underlying PD include alpha-synuclein misfolding and aggregation, impaired protein clearance, mitochondrial dysfunction, oxidative stress, and neuroinflammation. However, to date, no study has confirmed the specific pathogenesis of PD. Similarly, current PD treatment methods still have shortcomings. Although some emerging therapies have proved effective for PD, the specific mechanism still needs further clarification. Metabolic reprogramming, a term first proposed by Warburg, is applied to the metabolic energy characteristics of tumor cells. Microglia have similar metabolic characteristics. Pro-inflammatory M1 type and anti-inflammatory M2 type are the two types of activated microglia, which exhibit different metabolic patterns in glucose, lipid, amino acid, and iron metabolism. Additionally, mitochondrial dysfunction may be involved in microglial metabolic reprogramming by activating various signaling mechanisms. Functional changes in microglia resulting from metabolic reprogramming can cause changes in the brain microenvironment, thus playing an important role in neuroinflammation or tissue repair. The involvement of microglial metabolic reprogramming in PD pathogenesis has been confirmed. Neuroinflammation and dopaminergic neuronal death can effectively be reduced by inhibiting certain metabolic pathways in M1 microglia or reverting M1 cells to the M2 phenotype. This review summarizes the relationship between microglial metabolic reprogramming and PD and provides strategies for PD treatment.
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Enfermedades Neurodegenerativas , Enfermedad de Parkinson , Humanos , Enfermedad de Parkinson/metabolismo , Microglía/metabolismo , Enfermedades Neuroinflamatorias , Enfermedades Neurodegenerativas/metabolismo , Macrófagos/metabolismo , Neuronas Dopaminérgicas/metabolismoRESUMEN
We report on the experimental observation of the focusing effect of a 50MeV accelerator electron beam in a gas-discharge plasma target. The plasma is generated by igniting an electric discharge in two collinear quartz tubes, with the currents up to 1.5kA flowing in opposite directions in either of the two tubes. In such plasma current configuration, the electron beam is defocused in the first discharge tube and focused with a stronger force in the second one. With symmetric plasma currents, asymmetric effects are, however, induced on the beam transport process and the beam radius is reduced by a factor of 2.6 compared to the case of plasma discharge off. Experimental results are supported by two-dimensional particle-in-cell simulations.