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Capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) has proven to be an efficient technique for the separation and detection of charged inorganic, organic, and biochemical analytes. It offers several advantages, including cost-effectiveness, nanoliter injection volume, short analysis time, good separation efficiency, suitability for miniaturization, and portability. However, the routine determination of common inorganic cations (NH4+, K+, Na+, Ca2+, Mg2+, and Li+) and inorganic anions (F-, Cl-, Br-, NO2-, NO3-, PO43-, and SO42-) in water quality monitoring typically exhibits limits of detection of about 0.3-1 µM without preconcentration. This sensitivity often proves insufficient for the applications of CE-C4D in trace analysis situations. Here, we explore methods to push the detection limits of CE-C4D through a comprehensive consideration of signal and noise sources. In particular, we (i) studied the model of C4D and its guiding roles in C4D and CE-C4D, (ii) optimized the bandwidth and noise performance of the current-to-voltage (I-V) converter, and (iii) reduced the noise level due to the strong background signal of the background electrolyte by adaptive differential detection. We characterized the system with Li+; the 3-fold signal-to-noise (S/N) detection limit for Li+ was determined at 20 nM, with a linear range spanning from 60 nM to 1.6 mM. Moreover, the optimized CE-C4D method was applied to the analysis of common mixed inorganic cations (K+, Na+, Ca2+, Mg2+, and Li+), anions (F-, Cl-, Br-, NO2-, NO3-, PO43-, and SO42-), toxic halides (BrO3-) and heavy metal ions (Pb2+, Cd2+, Cr3+, Co2+, Ni2+, Zn2+, and Cu2+) at trace concentrations of 200 nM. All electropherograms showed good S/N ratios, thus proving its applicability and accuracy. Our results have shown that the developed CE-C4D method is feasible for trace ion analysis in water quality control.
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Evolutionary transitions from outcrossing to selfing in flowering plants have convergent morphological and genomic signatures and can involve parallel evolution within related lineages. Adaptive evolution of morphological traits is often assumed to evolve faster than nonadaptive features of the genomic selfing syndrome. We investigated phenotypic and genomic changes associated with transitions from distyly to homostyly in the Primula oreodoxa complex. We determined whether the transition to selfing occurred more than once and investigated stages in the evolution of morphological and genomic selfing syndromes using 22 floral traits and both nuclear and plastid genomic data from 25 populations. Two independent transitions were detected representing an earlier and a more recently derived selfing lineage. The older lineage exhibited classic features of the morphological and genomic selfing syndrome. Although features of both selfing syndromes were less developed in the younger selfing lineage, they exhibited parallel development with the older selfing lineage. This finding contrasts with the prediction that some genomic changes should lag behind adaptive changes to morphological traits. Our findings highlight the value of comparative studies on the timing and extent of transitions from outcrossing to selfing between related lineages for investigating the tempo of morphological and molecular evolution.
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Flores , Primula , Flores/genética , Flores/anatomía & histología , Genómica , Primula/genética , Evolución Biológica , Reproducción/genética , Polinización , Autofecundación/genéticaRESUMEN
Drought stress is one of the main environmental factors limiting plant growth and development. Plants adapt to changing soil moisture by modifying root architecture, inducing stomatal closure, and inhibiting shoot growth. The AP2/ERF transcription factor DREB2A plays a key role in maintaining plant growth in response to drought stress, but the molecular mechanism underlying this process remains to be elucidated. Here, it was found that overexpression of MdDREB2A positively regulated nitrogen utilisation by interacting with DRE cis-elements of the MdNIR1 promoter. Meanwhile, MdDREB2A could also directly bind to the promoter of MdSWEET12, which may enhance root development and nitrogen assimilation, ultimately promoting plant growth. Overall, this regulatory mechanism provides an idea for plants in coordinating with drought tolerance and nitrogen assimilation to maintain optimal plant growth and development under drought stress.
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Sequías , Proteínas de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Regiones Promotoras Genéticas , Sacarosa/metabolismo , Regulación de la Expresión Génica de las Plantas , Estrés Fisiológico/genéticaRESUMEN
The specific pathophysiological pathways through which diabetes exacerbates myocardial ischemia/reperfusion (I/R) injury remain unclear; however, dysregulation of immune and inflammatory cells, potentially driven by abnormalities in their number and function due to diabetes, may play a significant role. In the present investigation, we simulated myocardial I/R injury by inducing ischemia through ligation of the left anterior descending coronary artery in mice for 40 min, followed by reperfusion for 24 h. Previous studies have indicated that protein kinase Cß (PKCß) is upregulated under hyperglycemic conditions and is implicated in the development of various diabetic complications. The Y4 RNA fragment is identified as the predominant small RNA component present in the extracellular vesicles of cardio sphere-derived cells (CDCs), exhibiting notable anti-inflammatory properties in the contexts of myocardial infarction and cardiac hypertrophy. Our investigation revealed that the administration of Y4 RNA into the ventricular cavity of db/db mice following myocardial I/R injury markedly enhanced cardiac function. Furthermore, Y4 RNA was observed to facilitate M2 macrophage polarization and interleukin-10 secretion through the suppression of PKCß activation. The mechanism by which Y4 RNA affects PKCß by regulating macrophage activation within the inflammatory environment involves the inhibition of ERK1/2 phosphorylation In our study, the role of PKCß in regulating macrophage polarization during myocardial I/R injury was investigated through the use of PKCß knockout mice. Our findings indicate that PKCß plays a crucial role in modulating the inflammatory response associated with macrophage activation in db/db mice experiencing myocardial I/R, with a notable exacerbation of this response observed upon significant upregulation of PKCß expression. In vitro studies further elucidated the protective mechanism by which Y4 RNA modulates the PKCß/ERK1/2 signaling pathway to induce M2 macrophage activation. Overall, our findings suggest that Y4 RNA plays an anti-inflammatory role in diabetic I/R injury, suggesting a novel therapeutic approach for managing myocardial I/R injury in diabetic individuals.
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Modelos Animales de Enfermedad , Macrófagos , Ratones Endogámicos C57BL , Daño por Reperfusión Miocárdica , Proteína Quinasa C beta , Transducción de Señal , Animales , Proteína Quinasa C beta/metabolismo , Daño por Reperfusión Miocárdica/patología , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/prevención & control , Daño por Reperfusión Miocárdica/genética , Macrófagos/metabolismo , Macrófagos/enzimología , Masculino , Interleucina-10/metabolismo , Interleucina-10/genética , Ratones , Cardiomiopatías Diabéticas/enzimología , Cardiomiopatías Diabéticas/patología , Cardiomiopatías Diabéticas/metabolismo , Cardiomiopatías Diabéticas/etiología , Cardiomiopatías Diabéticas/genética , Cardiomiopatías Diabéticas/fisiopatología , Células Cultivadas , Fenotipo , Miocitos Cardíacos/enzimología , Miocitos Cardíacos/patología , Miocitos Cardíacos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Activación de Macrófagos , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Función Ventricular Izquierda , FosforilaciónRESUMEN
OBJECTIVE: Ubiquitin-specific peptidase 10 (USP10), a typical de-ubiquitinase, has been found to play a double-edged role in human cancers. Previously, we reported that the expression of USP10 was negatively correlated with the depth of gastric wall invasion, lymph node metastasis, and prognosis in gastric cancer (GC) patients. However, it remains unclear whether USP10 can regulate the metastasis of GC cells through its de-ubiquitination function. METHODS: In this study, proteome, ubiquitinome, and transcriptome analyses were conducted to comprehensively identify novel de-ubiquitination targets for USP10 in GC cells. Subsequently, a series of validation experiments, including in vitro cell culture studies, in vivo metastatic tumor models, and clinical sample analyses, were performed to elucidate the regulatory mechanism of USP10 and its de-ubiquitination targets in GC metastasis. RESULTS: After overexpression of USP10 in GC cells, 146 proteins, 489 ubiquitin sites, and 61 mRNAs exhibited differential expression. By integrating the results of multi-omics, we ultimately screened 9 potential substrates of USP10, including TNFRSF10B, SLC2A3, CD44, CSTF2, RPS27, TPD52, GPS1, RNF185, and MED16. Among them, TNFRSF10B was further verified as a direct de-ubiquitination target for USP10 by Co-IP and protein stabilization assays. The dysregulation of USP10 or TNFRSF10B affected the migration and invasion of GC cells in vitro and in vivo models. Molecular mechanism studies showed that USP10 inhibited the epithelial-mesenchymal transition (EMT) process by increasing the stability of TNFRSF10B protein, thereby regulating the migration and invasion of GC cells. Finally, the retrospective clinical sample studies demonstrated that the downregulation of TNFRSF10B expression was associated with poor survival among 4 of 7 GC cohorts, and the expression of TNFRSF10B protein was significantly negatively correlated with the incidence of distant metastasis, diffuse type, and poorly cohesive carcinoma. CONCLUSIONS: Our study established a high-throughput strategy for screening de-ubiquitination targets for USP10 and further confirmed that inhibiting the ubiquitination of TNFRSF10B might be a promising therapeutic strategy for GC metastasis.
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Neoplasias Gástricas , Ubiquitina Tiolesterasa , Ubiquitinación , Neoplasias Gástricas/patología , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Humanos , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Ratones , Animales , Línea Celular Tumoral , Movimiento Celular/genética , Regulación Neoplásica de la Expresión Génica , Femenino , Masculino , Metástasis de la Neoplasia , Perfilación de la Expresión Génica , Transición Epitelial-Mesenquimal/genética , Pronóstico , MultiómicaRESUMEN
Major depressive disorder (MDD) is a global health burden characterized by persistent low mood, deprivation of pleasure, recurrent thoughts of death, and physical and cognitive deficits. The current understanding of the pathophysiology of MDD is lacking, resulting in few rapid and effective antidepressant therapies. Recent studies have pointed to the sigma-1 (σ-1) receptor as a potential rapid antidepressant target; σ-1 agonists have shown promise in a variety of preclinical depression models. Hypidone hydrochloride (YL-0919), an independently developed antidepressant by our institute with faster onset of action and low rate of side effects, has recently emerged as a highly selective σ-1 receptor agonist; however, its underlying astrocyte-specific mechanism is unknown. In this study, we investigated the effect of YL-0919 treatment on gene expression in the prefrontal cortex of depressive-like mice by single-cell RNA sequencing. Furthermore, we knocked down σ-1 receptors on astrocytes in the medial prefrontal cortex of mice to explore the effects of YL-0919 on depressive-like behavior and neuroinflammation in mice. Our results demonstrated that astrocyte-specific knockdown of σ-1 receptor resulted in depressive-like behavior in mice, which was reversed by YL-0919 administration. In addition, astrocytic σ-1 receptor deficiency led to activation of the NF-κB inflammatory pathway, and crosstalk between reactive astrocytes and activated microglia amplified neuroinflammation, exacerbating stress-induced neuronal apoptosis. Furthermore, the depressive-like behavior induced by astrocyte-specific knockdown of the σ-1 receptor was improved by a selective NF-κB inhibitor, JSH-23, in mice. Our study not only reaffirms the σ-1 receptor as a key target of the faster antidepressant effect of YL-0919, but also contributes to the development of astrocytic σ-1 receptor-based novel drugs.
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Antidepresivos , Astrocitos , Trastorno Depresivo Mayor , Ratones Endogámicos C57BL , FN-kappa B , Corteza Prefrontal , Receptores sigma , Receptor Sigma-1 , Receptores sigma/metabolismo , Receptores sigma/agonistas , Animales , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Ratones , Corteza Prefrontal/metabolismo , Corteza Prefrontal/efectos de los fármacos , Antidepresivos/farmacología , FN-kappa B/metabolismo , Masculino , Trastorno Depresivo Mayor/metabolismo , Trastorno Depresivo Mayor/tratamiento farmacológico , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Modelos Animales de Enfermedad , Depresión/metabolismo , Depresión/tratamiento farmacológicoRESUMEN
Correction for 'A compact and high-performance setup of capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D)' by Lin Li et al., Analyst, 2024, https://doi.org/10.1039/d4an00354c.
RESUMEN
Capillary electrophoresis with capacitively coupled contactless conductivity detection (CE-C4D) has the advantages of high throughput (simultaneous detection of multiple ions), high separation efficiency (higher than 105 theoretical plates) and rapid analysis capability (less than 5 min for common inorganic ions). A compact CE-C4D system is ideal for water quality control and on-site analysis. It is suitable not only for common cations (e.g. Na+, K+, Li+, NH4+, Ca2+, etc.) and anions (e.g. Cl-, SO42-, BrO3-, etc.) but also for some ions (e.g. lanthanide ions, Pb2+, Cd2+, etc.) that require complex derivatization procedures to be detected by ion chromatography (IC). However, an obvious limitation of the CE-C4D method is that its sensitivity (e.g. 0.3-1 µM for common inorganic ions) is often insufficient for trace analysis (e.g. 1 ppb or 20 nM level for common inorganic ions) without preconcentration. For this technology to become a powerful and routine analytical technique, the system should be made compact while maintaining trace analysis sensitivity. In this study, we developed an all-in-one version of the CE-C4D instrument with custom-made modular components to make it a convenient, compact and high-performance system. The system was designed using direct digital synthesis (DDS) technology to generate programmable sinusoidal waveforms with any frequency for excitation, a kilovolt high-voltage power supply for capillary electrophoresis separation, and an "effective" differential C4D cell with a low-noise circuitry for high-sensitivity detection. We characterized the system with different concentrations of Cs+, and even a low concentration of 20 nM was detectable without preconcentration. Moreover, the optimized CE-C4D setup was applied to analyse mixed ions at a trace concentration of 200 nM with excellent signal-to-noise ratios. In typical applications, the limits of detection based on the 3σ criterion (without baseline filtering) were 9, 10, 24, 5, and 12 nM for K+, Cs+, Li+, Ca2+, and Mg2+, respectively, and about 7, 6, 6 and 6 nM for Br-, ClO4-, BrO3- and SO42-, respectively. Finally, the setup was also applied for the analysis of all 14 lanthanide ions and rare-earth minerals, and it showed an improvement in sensitivity by more than 25 times.
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Takifugu rubripes is a highly valued cultured fish in Asia, while pathogen infections can result in severe diseases and lead to substantial economic losses. Toll-like receptors (TLRs), as pattern recognition receptors, play a crucial role on recognition pathogens and initiation innate immune response. However, the immunological properties of teleost-specific TLR23 remain largely unknown. In this study, we investigated the biological functions of TLR23 (TrTLR23) from T. rubripes, found that TrTLR23 existed in various organs. Following bacterial pathogen challenge, the expression levels of TrTLR23 were significantly increased in immune related organs. TrTLR23 located on the cellular membrane and specifically recognized pathogenic microorganism. Co-immunoprecipitation and antibody blocking analysis revealed that TrTLR23 recruited myeloid differentiation primary response protein (MyD88), thereby mediating the activation of the ERK signaling pathway. Furthermore, in vivo showed that, when TrTLR23 is overexpressed in T. rubripes, bacterial replication in fish tissues is significantly inhibited. Consistently, when TrTLR23 expression in T. rubripes is knocked down, bacterial replication is significantly enhanced. In conclusion, these findings suggested that TrTLR23 played a critical role on mediation TLR23-MyD88-ERK axis against bacterial infection. This study revealed that TLR23 involved in the innate immune mechanism, and provided the foundation for development disease control strategies in teleost.
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Enfermedades de los Peces , Proteínas de Peces , Inmunidad Innata , Factor 88 de Diferenciación Mieloide , Takifugu , Receptores Toll-Like , Animales , Proteínas de Peces/genética , Proteínas de Peces/inmunología , Takifugu/inmunología , Takifugu/genética , Enfermedades de los Peces/inmunología , Factor 88 de Diferenciación Mieloide/genética , Factor 88 de Diferenciación Mieloide/metabolismo , Factor 88 de Diferenciación Mieloide/inmunología , Inmunidad Innata/genética , Receptores Toll-Like/genética , Receptores Toll-Like/inmunología , Receptores Toll-Like/metabolismo , Sistema de Señalización de MAP Quinasas/inmunología , Regulación de la Expresión Génica/inmunología , Edwardsiella/fisiología , Edwardsiella/inmunología , Vibrio/fisiologíaRESUMEN
3-Methylindole (Skatole), a degradation product of tryptophan produced by intestinal microbial activity, significantly contributes to odor nuisance. Its adverse effects on animal welfare, human health, and environmental pollution have been noted. However, it is still unclear whether the intestinal microbiota mediates the impact of selenium (Se) on skatole production and what the underlying mechanisms remain elusive. A selenized glucose (SeGlu) derivative is a novel organic selenium compound. In this study, a diverse range of dietary SeGlu-treated levels, including SeGlu-deficient (CK), SeGlu-adequate (0.15 mg Se per L), and SeGlu-supranutritional (0.4 mg Se per L) conditions, were used to investigate the complex interaction of SeGlu on intestinal microbiome and serum metabolome changes in male Sprague-Dawley (SD) rats. The study showed that SeGlu supplementation enhanced the antioxidant ability in rats, significantly manifested in the increases of the activity of catalase (CAT) and glutathione peroxidase (GSH-Px), while no change in the level of malonaldehyde (MDA). Metagenomic sequencing analysis verified that the SeGlu treatment group significantly increased the abundance of beneficial microorganisms such as Clostridium, Ruminococcus, Faecalibacterium, Lactobacillus, and Alloprevotella while reducing the abundance of opportunistic pathogens such as Bacteroides and Alistipes significantly. Further metabolomic analysis revealed phenylalanine, tyrosine, and tryptophan biosynthesis changes in the SeGlu treatment group. Notably, the biosynthesis of indole, a critical pathway, was affected by SeGlu treatment, with several crucial enzymes implicated. Correlation analysis demonstrated strong associations between specific bacterial species - Treponema, Bacteroides, and Ruminococcus, and changes in indole and derivative concentrations. Moreover, the efficacy of SeGlu-treated fecal microbiota was confirmed through fecal microbiota transplantation, leading to a decrease in the concentration of skatole in rats. Collectively, the analysis of microbiota and metabolome response to diverse SeGlu levels suggests that SeGlu is a promising dietary additive in modulating intestinal microbiota and reducing odor nuisance in the livestock and poultry industry.
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Microbioma Gastrointestinal , Glucosa , Ratas Sprague-Dawley , Escatol , Triptófano , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Escatol/metabolismo , Masculino , Triptófano/metabolismo , Ratas , Glucosa/metabolismo , Selenio/farmacología , DietaRESUMEN
BACKGROUND: Adherence to healthy lifestyle habits has become a mainstream approach for lessening the burden of cardiovascular disease (CVD) during initial prevention efforts. The purpose of this study was to investigate the prevalence of four healthy lifestyle habits, the associated factors, and their impact on all-cause and cardiovascular mortality among residents of Guangxi Zhuang Autonomous Region. METHODS: From 2015 to 2019, individuals between the ages of 35 and 75 from Guangxi Zhuang Autonomous Region were recruited through the ChinaHeart Million Person Project. Our study examined four healthy lifestyle habits: not smoking, no or moderate amounts of alcohol, sufficient leisure time physical activity (LTPA) and a balanced diet. RESULTS: Out of the 19,969 individuals involved, the majority, 77.3% did not smoke, while 96.7% had limited alcohol intake, 24.5% engaged in sufficient LTPA, 5.5% followed a balanced diet, and merely 1.7% adhered to all four healthy lifestyle habits. Participants who were women, older, nonfarmers, living in cities, with a high income or level of education, or had hypertension or diabetes were more likely to follow all four healthy lifestyle habits (p < 0.001). People who followed the three healthy lifestyle habits had reduced chances of death from all cause (HR 0.34[95% CI:0.15,0.76]) and cardiovascular-related death (HR 0.23 [95% CI: 0.07, 0.68]) (p < 0.01) over a median period of 3.5 years. CONCLUSIONS: In Guangxi Province, the level of adherence to healthy lifestyle habits is very minimal. Therefore, population-specific health promotion strategies are urgently needed.
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Enfermedades Cardiovasculares , Estilo de Vida Saludable , Humanos , Masculino , Femenino , Persona de Mediana Edad , China/epidemiología , Enfermedades Cardiovasculares/mortalidad , Adulto , Anciano , Ejercicio Físico , Causas de Muerte , Consumo de Bebidas Alcohólicas/epidemiologíaRESUMEN
BACKGROUND: Quitting support from smokers' partners can predict quit attempts and smoking abstinence but research on factors that predict such support has been limited. To add more evidence for partner support and the improved interventions for smoking cessation, we analyzed some new potential predictors of quitting support from smokers' spouses. METHOD: This cross-sectional study was conducted in in 2022 and 2023, selecting the students' families in which fathers smoked and mothers didn't smoke from grade 1-5 of 13 primary schools in Qingdao, China. Parents who met the criteria completed the online questionnaires and 1018 families were included in the analysis. We measured personal information related to smokers and their spouses such as age, education and nicotine dependence, and variables related to family and marital relationship such as family functioning, perceived responsiveness and power in decision-making of quitting smoking. Quitting support from smokers' spouses was measured by Partner Interaction Questionnaire and generalized linear model was used to explore the potential predictors of partner support. RESULTS: In this study, the mean age of smokers was 39.97(SD = 5.57) and the mean age of smokers' spouses was 38.24(SD = 4.59). The regression analysis showed that for smokers and their spouses, the older age groups showed the lower ratio of positive/negative support(P < 0.05) and smokers with high education showed the less positive and negative partner support(P < 0.05). Nicotine dependence was positively associated with negative support (ß = 0.120, P < 0.01), and perceived responsiveness (ß = 0.124, P < 0.05) as well as family functioning (ß = 0.059, P < 0.05) was positively associated with positive support. These three factors were associated with ratio of positive/negative support(P < 0.05). In addition, power of smoker's spouse in decision-making of quitting smoking was positively associated with the positive (ß = 0.087, P < 0.001) and negative support (ß = 0.084, P < 0.001). CONCLUSIONS: Nicotine dependence, family functioning, power in decision-making of quitting smoking and perceived responsiveness were found to be the predictors of quitting support from smokers' spouses. By incorporating predictors of partner support and integrating some established theories that can improve family functioning and marital relationships, smoking cessation interventions can be further improved.
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Tabaquismo , Humanos , Masculino , Anciano , Estudios Transversales , Fumar , China/epidemiología , PadreRESUMEN
BACKGROUND: With Primary Health Care (PHC) being a cornerstone of accessible, affordable, and effective healthcare worldwide, its efficiency, especially in developing countries like China, is crucial for achieving Universal Health Coverage (UHC). This study evaluates the efficiency of PHC systems in a southwest China municipality post-healthcare reform, identifying factors influencing efficiency and proposing strategies for improvement. METHODS: Utilising a 10-year provincial panel dataset, this study employs an enhanced Data Envelopment Analysis (DEA) model integrating Slack-Based Measure (SBM) and Directional Distance Function (DDF) with the Global Malmquist-Luenberger (GML) index for efficiency evaluation. Tobit regression analysis identifies efficiency determinants within the context of China's healthcare reforms, focusing on horizontal integration, fiscal spending, urbanisation rates, and workforce optimisation. RESULTS: The study reveals a slight decline in PHC system efficiency across the municipality from 2009 to 2018. However, the highest-performing county achieved a 2.36% increase in Total Factor Productivity (TFP), demonstrating the potential of horizontal integration reforms and strategic fiscal investments in enhancing PHC efficiency. However, an increase in nurse density per 1,000 population negatively correlated with efficiency, indicating the need for a balanced approach to workforce expansion. CONCLUSIONS: Horizontal integration reforms, along with targeted fiscal inputs and urbanisation, are key to improving PHC efficiency in underdeveloped regions. The study underscores the importance of optimising workforce allocation and skillsets over mere expansion, providing valuable insights for policymakers aiming to strengthen PHC systems toward achieving UHC in China and similar contexts.
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Eficiencia Organizacional , Reforma de la Atención de Salud , Atención Primaria de Salud , China , HumanosRESUMEN
The persistence of the novel brominated flame retardant, bis(2-ethylhexyl)-3,4,5,6-tetrabromophthalate (TBPH), in the environment and its potential for bioaccumulation in living organisms, including humans, further exacerbate its health risks. Therefore, ongoing research is crucial for fully understanding the extent of TBPH's neurotoxicity and for developing effective mitigation strategies. This study aims to investigate the potential neurotoxicity of TBPH on mouse neurobehavior and to evaluate the protective effects of the natural antioxidant astaxanthin (AST) against TBPH-induced neurotoxicity. The results indicate that exposure to TBPH can lead to a decline in learning and memory abilities and abnormal behaviors in mice, which may be associated with oxidative stress responses and apoptosis in the hippocampus. TBPH may disrupt the normal function of hippocampal neurons by activating the extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. Mice exposed to TBPH treated with AST showed improved learning and memory abilities in the Morris water maze (MWM) and Step-down test (SDT). AST, through its antioxidant action, was able to significantly reduce the increase in reactive oxygen species (ROS) levels induced by TBPH, the increased expression of apoptosis markers, and the activation of the ERK1/2-FOS signaling pathway, alleviating TBPH-induced apoptosis in hippocampal neurons and improving neurobehavioral outcomes. These findings suggest that AST may alleviate the neurotoxicity of TBPH by modulating molecular events related to apoptosis and the ERK1/2-FOS signaling pathway. Thus, this study provides evidence for AST as a potential interventional strategy for the prevention or treatment of cognitive decline associated with environmental neurotoxicant exposure.
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Hipocampo , Sistema de Señalización de MAP Quinasas , Especies Reactivas de Oxígeno , Xantófilas , Animales , Xantófilas/farmacología , Ratones , Especies Reactivas de Oxígeno/metabolismo , Hipocampo/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Conducta Animal/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Retardadores de Llama/toxicidad , Antioxidantes/farmacología , Ácidos Ftálicos/toxicidad , Apoptosis/efectos de los fármacos , Neuronas/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacosRESUMEN
Propylene glycol (PG) and vegetable glycerin (VG) are the most common solvents used in electronic cigarette liquids. No long-term inhalation toxicity assessments have been performed combining conventional and multi-omics approaches on the potential respiratory effects of the solvents in vivo. In this study, the systemic toxicity of aerosol generated from a ceramic heating coil-based e-cigarette was evaluated. First, the aerosol properties were characterized, including carbonyl emissions, the particle size distribution, and aerosol temperatures. To determine toxicological effects, rats were exposed, through their nose only, to filtered air or a propylene glycol (PG)/ glycerin (VG) (50:50, %W/W) aerosol mixture at the target concentration of 3 mg/L for six hours daily over a continuous 28-day period. Compared with the air group, female rats in the PG/VG group exhibited significantly lower body weights during both the exposure period and recovery period, and this was linked to a reduced food intake. Male rats in the PG/VG group also experienced a significant decline in body weight during the exposure period. Importantly, rats exposed to the PG/VG aerosol showed only minimal biological effects compared to those with only air exposure, with no signs of toxicity. Moreover, the transcriptomic, proteomic, and metabolomic analyses of the rat lung tissues following aerosol exposure revealed a series of candidate pathways linking aerosol inhalation to altered lung functions, especially the inflammatory response and disease. Dysregulated pathways of arachidonic acids, the neuroactive ligand-receptor interaction, and the hematopoietic cell lineage were revealed through integrated multi-omics analysis. Therefore, our integrated multi-omics approach offers novel systemic insights and early evidence of environmental-related health hazards associated with an e-cigarette aerosol using two carrier solvents in a rat model.
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Sistemas Electrónicos de Liberación de Nicotina , Glicerol , Masculino , Femenino , Ratas , Animales , Glicerol/toxicidad , Glicerol/análisis , Verduras , Multiómica , Proteómica , Propilenglicol/toxicidad , Propilenglicol/análisis , Solventes , Aerosoles/análisisRESUMEN
OBJECTIVE: To systematically review the risk factors for unplanned weaning during continuous renal replacement therapy in ICU patients. METHODS: A combination of subject words + free words was used to search the relevant literature published in CNKI, Wanfang, VIP, CBM, PubMed, EMbase, Web of Science, Cochrane Library, Mediline and other databases. The search period was from the establishment of the databases to June 25, 2024. Revman 5.4 software and Stata15.0 software was used to meta-analyze the risk factors for unplanned weaning during continuous renal replacement therapy in ICU patients. RESULTS: A total of 23 studies were included in this meta-analysis, describing 15 variables, 3793 patients, and using 7197 filters. Meta-analysis results showed that risk factors for unplanned weaning during continuous renal replacement therapy in ICU patients were as follows: Low mean arterial pressure [OR = 1.02, 95%CI (1.00, 1.03), p < 0.05], hypothermia [OR = 3.40, 95%CI (1.78, 6.47), p < 0.05], age (≥60 years) [OR = 4.45, 95%CI (3.18, 6.22), p < 0.05], comorbid underlying disease [OR = 3.63, 95%CI (2.70, 4.88), p < 0.05], agitation [OR = 4.97, 95%CI (3.20, 7.74), p < 0.05], no anticoagulant use [OR = 1.65, 95%CI (1.25, 2.17), p < 0.05], short activated partial prothrombin time [OR = 1.23, 95%CI (1.13, 1.34), p < 0.05], hyper-hematocrit [OR = 1.73, 95%CI (1.13, 2.66), p = 0.01], low ionized calcium concentration [OR = 1.48, 95% CI (1.08, 2.02), p = 0.01], CRRT that was treated at a high dose [OR = 1.42, 95%CI (1.14, 1.76), p < 0.05], mechanical ventilation [OR = 4.25, 95%CI (2.67, 6.77), p < 0.05], and lack of dedicated care [OR = 5.08, 95%CI (2.51, 10.28), p < 0.05]. However, it is unclear whether platelet count, prothrombin activity, and blood flow velocity are risk factors for unplanned weaning during CRRT in ICU patients, and more studies are needed for further validation. CONCLUSION: Available evidence suggests that a variety of factors contribute to unplanned weaning of CRRT in ICU patients. Early detection of these risk factors is essential for healthcare professionals to develop preventive and curative strategies. REGISTRATION: This study is registered on the PROSERO website under registration number CRD42024543554.
Asunto(s)
Terapia de Reemplazo Renal Continuo , Unidades de Cuidados Intensivos , Humanos , Factores de Riesgo , Lesión Renal Aguda/terapiaRESUMEN
OBJECTIVES: The aim of this study was to determine the strength of the association between frailty and adverse outcomes in patients undergoing maintenance hemodialysis. DESIGN: A systematic review and meta-analysis. SETTING AND PARTICIPANTS: Patients aged ≥18 years who were undergoing maintenance hemodialysis. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, Scopus, the China Knowledge Resource Integrated Database, the Wanfang Database and the Weipu Database were searched from inception until 11 April 2024. The reviewers independently selected the studies, extracted the data and evaluated the quality of the studies. Stata 15.1 software was used to perform the meta-analysis. RESULTS: A total of 36 articles were included in this study, including 56,867 patients. The primary outcome events in this study were mortality, hospitalization, and vascular access events. The secondary outcomes were depression, cognitive impairment, falls, fracture, sleep disturbances, and quality of life. This study suggested that frailty was associated with mortality in patients undergoing maintenance hemodialysis [hazard ratio (HR), 1.97; 95% CI, 1.62-2.40]. Frailty increased the risk of mortality in patients [odds ratio (OR), 2.33; 95% CI, 1.47-3.68]. In addition, we found that frailty was significantly associated with hospitalization in patients undergoing maintenance hemodialysis (OR, 2.47; 95% CI, 1.52-4.03). Patients who were undergoing maintenance hemodialysis and who were frail had a greater risk of hospitalization [RR, 1.47; 95% CI, 1.05-2.08] and emergency visits (RR, 2.28; 95% CI, 1.78-2.92). The results of this study also suggested that frailty was associated with a greater risk of vascular access events (HR, 1.72; 95% CI, 1.50-1.97). Finally, frailty increased the risk of depression (OR, 4.31; 95% CI, 1.83-10.18), falls and fractures, and reduced quality of life. CONCLUSIONS: The findings of this study suggested that frailty was an important predictor of adverse outcomes in patients undergoing maintenance hemodialysis. In the future, medical staff should regularly evaluate signs of weakness, formulate individual diagnosis and treatment plans, adjust dialysis plans according to the patient's condition, and reduce the occurrence of adverse events. REGISTRATION: The study protocol was registered on PROSPERO (https://www.crd.york.ac.uk/PROSPERO/, number: CRD42023486239).
Asunto(s)
Fragilidad , Hospitalización , Fallo Renal Crónico , Calidad de Vida , Diálisis Renal , Humanos , Diálisis Renal/efectos adversos , Fragilidad/epidemiología , Hospitalización/estadística & datos numéricos , Fallo Renal Crónico/terapia , Fallo Renal Crónico/mortalidad , Fallo Renal Crónico/complicaciones , Accidentes por Caídas/estadística & datos numéricos , Depresión/epidemiología , Depresión/etiología , Factores de RiesgoRESUMEN
Environmental temperatures are increasing worldwide, threatening desert ectotherms already living at their thermal limits. Organisms with flexible thermoregulatory behaviours may be able to mitigate the effects of extreme temperatures by moving among microhabitats, yet little work has tracked movement patterns of desert ectotherms in the wild over diurnal scales or compared behaviour among seasons. Here, we used camera traps to track the thermoregulatory behaviour and microhabitat choices of 30 desert lizards (Messalina bahaldini) in custom, outdoor arenas that provided access to open, rock, and bush microhabitats. We found that in the summer, lizards preferred to move to the shaded microhabitats and remain there under warmer conditions. During winter, however, lizards' activity was not related to temperature, and lizards mostly chose to remain in the open habitat. Interestingly, in both seasons, lizards tended to remain in their current microhabitat and moved infrequently between certain combinations of microhabitats. Our study shows that thermoregulation (shade-seeking behaviour) is a major factor during summer, helping lizards to avoid extreme temperatures, but not during winter, and shows a novel effect of current microhabitat on movement, suggesting that other biotic or abiotic factors may also drive microhabitat choice. Understanding the complex factors at play in microhabitat choice is critical for developing conservation programs that effectively mitigate the negative impacts of climate change on desert animals.
Asunto(s)
Regulación de la Temperatura Corporal , Clima Desértico , Lagartos , Estaciones del Año , Animales , Lagartos/fisiología , Ecosistema , Conducta Animal , Movimiento , MasculinoRESUMEN
CONTEXT: Molecular dynamics simulations are performed to clarify the deformation mechanism of ß-HMX crystal in the [Formula: see text] space group setting under uniaxial compression. Nanoscale shear bands whose internal structure is regular enough to form twin with parent structure were found under high strain rate loading in the [010] direction. These deformation twins are formed by the change of lattice orientation due to atomic translation under shear stress, with [Formula: see text] (or [Formula: see text] twin planes and [Formula: see text] (or [Formula: see text] twin directions. Molecular rotation can significantly reduce the activation barrier of twin systems; meanwhile, the change of lattice direction is accomplished by a serial of fractional translation steps. Our results implicate that these factors, such as decreasing the activation energy barrier of twin systems via molecular rotation and new twin systems introducing shear bands, should be considered via applying the crystal plasticity model to investigate the hot spot formation in energetic explosive crystals. METHODS: All simulations were carried out with the MD code package LAMMPS. The non-reactive and flexible molecular force field proposed by Smith and Bharadwaj was adopted to simulate the uniaxial compression of the monoclinic ß-HMX molecular crystal in the [Formula: see text] space group setting on (010) plane along [010] direction. In addition, the Shake algorithm was used to constrain all C-H bonds to the equilibrium length. Two methods, i.e., the Von Mises strain and the relative displacements of molecules, were applied to analyze the structure of twin type shear bands of ß-HMX during compression. Visualization analysis for atomistic simulations was performed by using OVITO.
RESUMEN
Ni is a promising B-site doping element capable of improving the oxygen carrier performance of SrFeO3 perovskite. In this work, the effect of Ni doping on the formation and migration of oxygen vacancies in SrFe1-xNixO3-δ (x = 0, 0.0625, 0.125, 0.1875, and 0.25) is investigated using density functional theory calculations. Our results show that the oxygen vacancies formed from Ni-O-Fe chains exhibit lower formation energy (Ef) compared to those from Fe-O-Fe chains in each doping system. Additionally, Ef generally decreases with an increase of Ni content. This Ni-promoted formation of VO is attributed to three factors: weakened Ni-O bonding, the closure of O-2p states to the Fermi level by Ni-O hybridization, and Ni3+ decreasing the positive charges to be compensated by VO formation. Due to these multiple advantages, a modest Ni doping of x = 0.25 can induce a higher PO2 and a lower T comparted to the relatively larger Co doping of x = 0.5, thermodynamically. Kinetically, Ni-doping appears to be a disadvantage as it hinders oxygen migration, due to a higher oxygen migration barrier through SrSrNi compared to the SrSrFe pathway. However, the overall oxygen ion conduction would not be significantly influenced by hopping through a nearby pathway of SrSrFe with a low migration barrier in a system doped with a small amount of Ni. In a word, a small amount of Ni doping has an advantage over Co doping in terms of enhancing the oxygen carrier performance of the parent SrFeO3 system.