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China is currently entering a stage of high-quality development, with urban development and governance facing systematic reconstruction of internal and external conditions, showing clear differences and the complex superposition of multi-stage development. The steady progress of urbanization has facilitated significant changes in the population structure of Chinese cities. It is expected that the population and industries will further converge to urban agglomerations and big cities, indicating basic multicenter and network patterns. Therefore, analyzing the negative population growth risks of urban agglomerations at different development stages is crucial. This study examined the cities of 19 urban agglomerations in China by adopting the data of the seventh population census, employing the optimized fuzzy logic method, building a complex network of population flow with ArcGIS and MATLAB platforms, and using the intensity of population flow and the registered population fertility rate to represent exogenous and endogenous growth, respectively. The negative population growth evaluation index system was constructed with five indicators: child ratio, aging rate, average family size, population density, and sex ratio. The risk index of negative population growth was measured using the fuzzy logic method, and the growth mechanism of negative population growth risk in urban agglomerations in China was analyzed using the spatial measurement method. (1) The negative population growth risk of growing urban agglomerations was influenced by both exogenous and endogenous growth, with exogenous growth having a greater impact. (2) The dynamic mechanism of negative population growth risk in large urban agglomerations is exogenous growth, whereas that of nurturing urban agglomerations is endogenous growth. (3) According to the risk of negative population growth in China's urban agglomerations and its influencing factors, negative population growth in 19 urban agglomerations can be divided into eight types. 1) The state of population growth of expanding urban agglomerations can be divided into two types, with the middle reaches of the Yangtze River and Chengdu-Chongqing urban agglomerations as one type; the capital city has a low risk of negative population growth, while other cities have a high risk of negative population growth. The Yangtze River Delta, Pearl River Delta, and Beijing-Tianjin-Hebei city clusters are the same, with the capital and other cities having a relatively low risk of negative population growth. 2) The status of large urban agglomerations can be divided into two types: Shandong Peninsula, Central Plains, Guanzhong Plain, and Beibu Gulf urban agglomerations. The capital city has a low risk of negative population growth, whereas other cities have a high risk of negative population growth. The risk of negative population growth in capital cities and other cities is relatively low. 3) The state of population growth of cultivated urban agglomerations can be divided into four types: the Harbin and Changsha urban agglomerations and the central and southern Liaoning urban agglomerations, which have a high risk of negative population growth. Meanwhile, the northern slope of the Tianshan Mountain City cluster and the Hubao Eyu City cluster have low risk of negative population growth. The risk of negative population growth is low in the provincial capital city and high in the other cities, while endogenous growth is positive in the provincial capital city and negative in the other cities. In the Jinzhong City, Central Guizhou City, and Central Yunnan City groups, the risk of negative population growth is low in provincial cities and high in other cities. Endogenous growth shows that the capital city and other cities have positive growth. In conclusion, this study posits that upgrading urban agglomerations should consider the spatial balance of population distribution, large urban agglomerations should fulfill their role in "blocking the flow" of big cities, and nurturing urban agglomerations should "consolidate human capital." This study presents a comprehensive and in-depth analysis of the negative population growth risk and its impact mechanisms in different development stages of urban agglomerations. This can provide a decision-making reference for the formulation of scientific and reasonable population and economic policies in various urban agglomerations and plays a significant role for maintaining a long-term stable population, economy, and social growth in the region.

Pancreatic β-cell dysfunction caused by obesity can be associated with alterations in the levels of miRNAs. However, the role of miRNAs in such processes remains elusive. Here, we show that pancreatic islet miR-27a-5p, which is markedly increased in obese mice and impairs insulin secretion, is mainly delivered by visceral adipocyte–derived extracellular vesicles (EVs). Depleting miR-27a-5p significantly improved insulin secretion and glucose intolerance in db / db mice. Supporting the function of EV miR-27a-5p as a key pathogenic factor, intravenous injection of miR-27a-5p–containing EVs showed their distribution in mouse pancreatic islets. Tracing the injected adeno-associated virus (AAV)-miR-27a-5p (AAV-miR-27a) or AAV-FABP4-miR-27a-5p (AAV-FABP4-miR-27a) in visceral fat resulted in upregulating miR-27a-5p in EVs and serum and elicited mouse pancreatic β-cell dysfunction. Mechanistically, miR-27a-5p directly targeted L-type Ca2+ channel subtype CaV1.2 (Cacna1c) and reduced insulin secretion in β-cells. Overexpressing mouse CaV1.2 largely abolished the insulin secretion injury induced by miR-27a-5p. These findings reveal a causative role of EV miR-27a-5p in visceral adipocyte–mediated pancreatic β-cell dysfunction in obesity-associated type 2 diabetes mellitus. Article Highlights: miR-27a-5p expression in the islets is increased in obesity-associated diabetes mouse models. miR-27a-5p overexpression in β-cells impairs β-cell function in vitro and in vivo. Visceral adipocyte–derived extracellular vesicles and their cargo miR-27a-5p lead to β-cell insulin secretion injury and glucose intolerance by targeting L-type Ca2+ channel subtype CaV1.2. Blockage of visceral adipocyte extracellular vesicle miR-27a-5p expression improves β-cell insulin secretion and glucose tolerance in db / db mice. [ABSTRACT FROM AUTHOR]

Aim: To assess the expression and function of miR‐483‐5p in diabetic β cells. Methods: The expression of miR‐483‐5p was evaluated in the pancreatic islets of obesity mouse models by quantitative reverse transcription polymerase chain reaction. Dual‐luciferase activity, and western blotting assays, were utilized for miR‐483‐5p target gene verification. Mice with β cell‐specific miR‐483‐5p downregulation were studied under metabolic stress (i.e. a high‐fat diet) condition. Lineage tracing was used to determine β‐cell fate. Results: miR‐483‐5p increased in the islets of obese mouse models. Expression levels of miR‐483‐5p were significantly upregulated with the treatment of high glucose and palmitate, in both MIN6 cells and mouse islets. Overexpression of miR‐483‐5p in β cells results in impaired insulin secretion and β‐cell identity. Cell lineage‐specific analyses revealed that miR‐483‐5p overexpression deactivated β‐cell identity genes (insulin, Pdx1 and MafA) and derepressed β‐cell dedifferentiation (Ngn3) genes. miR‐483‐5p downregulation in β cells of high‐fat diet‐fed mice alleviated diabetes and improved glucose intolerance by enhancing insulin secretory capacity. These detrimental effects of miR‐483‐5p relied on its seed sequence recognition and repressed expression of its target genes Pdx1 and MafA, two crucial markers of β‐cell maturation. Conclusions: These findings indicate that the miR‐483‐5p–mediated reduction of mRNAs specifies β‐cell identity as a contributor to β‐cell dysfunction via the loss of cellular differentiation. [ABSTRACT FROM AUTHOR]

Understanding the near-ground vertical and temporal photochemical O 3 formation mechanism is important to mitigate O 3 pollution. Here, we measured the vertical profiles of O 3 and its precursors at six different heights, ranging from 5 to 335 m, using a newly built vertical observation system in the Pearl River Delta (PRD) region of China. The net photochemical ozone production rate (P (O 3) net) and O 3 formation sensitivities at various heights were diagnosed using an observation-based model coupled with the Master Chemical Mechanism (MCM v3.3.1). Moreover, to assess model performance and identify the causative factors behind O 3 pollution episodes, the P (O 3) net was measured at 5 m above ground level with a custom-built detection system. In total, three O 3 pollution episodes and two non-episodes were captured. The identified O 3 pollution episodes were found to be jointly influenced by both photochemical production and physical transport, with local photochemical reactions playing a major role. The high index of agreement (IOA) calculated by comparing the modelled and measured P (O 3) net values indicated the rationality of investigating the vertical and temporal variability in O 3 formation mechanisms using model results. However, the measured P (O 3) net values were generally higher than the modelled P (O 3) net values, particularly under high-NO x conditions, which may indicate a potential underestimation of total RO 2 by the model. Throughout the measurement period, the contribution of different reaction pathways to O 3 production remained consistent across various heights, with HO 2 + NO as the major O 3 production pathway, followed by RO 2 + NO. We observed that P (O 3) net decreased with an increase in measurement height, which was primarily attributed to the reduction in O 3 precursors, such as oxygenated volatile organic compounds (OVOCs) and non-methane hydrocarbons (NMHCs). The O 3 formation regimes were similar at different heights during both episodes and non-episodes, either being located in the VOC-sensitive regime or in the transition regime that is more sensitive to VOCs. Diurnally, photochemical O 3 formation typically remained in the VOC-sensitive regime during the morning and noon, but it transitioned to the transition regime and was more sensitive to VOCs in the afternoon at around 16:00 LT (local time). Vertical and temporal photochemical O 3 formation is most sensitive to OVOCs, suggesting that targeting specific VOCs for control measures is more practical and feasible at the observation site. The vertical temporal analysis of O 3 formation mechanisms near the ground surface in this study provides critical foundational knowledge that can be used to formulate effective short-term emergency and long-term control strategies to combat O 3 pollution in the PRD region of China. [ABSTRACT FROM AUTHOR]

Activated carbon filter is the main equipment used to remove pollutants in the ventilation system in a nuclear power plant. Its main function is to remove radioactive iodine to minimize radioactive hazards against workers in the ventilation area. Periodic evaluation is a key step for verifying its operation effectiveness, further to ensure the safety and long-term operation. In this paper, by changing the micropore structure and surface chemical properties of activated carbon, its physicochemical properties and adsorption performance against methyl iodide under the high humidity working environment are studied. The results show that the adsorption performance of activated carbon on organic compound decreases significantly under the high humidity conditions; however, the combination of potassium iodide, triethylene diamine and functional groups on the activated carbon surface form stable chemical bonds and a new surface structure, which enhances the adsorption performance and stability of activated carbon against pollutants and makes it difficult to remove pollutants. The adsorption capacity of nuclear activated carbon can be restored to 80.7% of the initial capacity, and the adsorption performance can be obviously improved.

Objective: To investigate the therapeutic effect and mechanism of sivelestat sodium on acute lung injury (AIL). Methods: A rat model for ALI/acute respiratory distress syndrome (ALI/ARDS) was established. Pathological examination of lung tissue was conducted to assess lung injury. Blood gas in the arteries was measured using a blood analyzer. Changes in PaO2, PaO2/FiO2, and lung wet/dry (W/D) weight ratio were carefully compared. ELISA assay was conducted to estimate cell adhesion and inflammation response. Finally, real-time reverse transcription polymerase chain reaction and western blotting assay was used to determine the activation of PI3K/AKT/mTOR pathway. Results: ARDS in vivo model was successfully constructed by LPS injection. Compared with the sham group, PaO2 and PaO2/FiO2 were significantly lower in the vehicle group, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8 andTNF-αwere significantly increased. After treatment with different doses of sivelestat sodium, we found PaO2, PaO2/FiO2 were prominently increased, while the lung W/D ratio, the lung injury score, NE, VCAM-1, IL-8, TNF-α levels were decreased in the dose-dependent manner. Meanwhile, compared with the vehicle group, the expression levels of Bax, PI3K, Akt and mTOR were significantly lower, and the expression of Bcl-2 was significantly higher after injection with sivelestat sodium. Conclusion: Sivelestat sodium has an interventional effect on ALI in sepsis by inhibiting the PI3K/AKT/mTOR signalling pathway. [ABSTRACT FROM AUTHOR]

Understanding the near-ground vertical and temporal photochemical O3 formation mechanism is important to mitigate the O3 pollution. Here, we measured the vertical profiles of O3 and its precursors at six different heights from 5-335 m using a newly built vertical observation system in Pearl River Delta (PRD) region, China. The net photochemical ozone production rate (P (O3)net) and O3 formation sensitivities at various heights were diagnosed using an observation-based model coupled with the Master Chemical Mechanism (MCM v3.3.1). Moreover, for the assessment of model performance and the causative factors behind O3 pollution episodes, the net photochemical ozone production rate (P (O3)net) was measured at 5 m ground level utilizing a custom-built detection system. In total three O3 pollution episodes and two non-episodes were captured. The identified O3 pollution episodes were found to be jointly influenced by both photochemical production and physical transport, with local photochemical reactions play a dominate role. The high index of agreement (IOA) calculated from comparing the modelled and measured P (O3)net values indicated the rationality to investigate the vertical and temporal variability of O3 formation mechanism using modelling results. However, the measured P (O3)net values were generally higher than the modelled P (O3)net values, particularly under high NOx conditions, which may indicate a potential underestimation of total RO2 by the model. Throughout the measurement period, the contribution of different reaction pathways to O3 production remained consistent across various heights, with HO2+NO as the major O3 production pathway, followed by RO2+NO. We saw P (O3)net decreased with the increase of the measurement height, primarily attributed to the decreased O3 precursors anthropogenic organic compounds (AVOC) and oxygenated volatile organic compounds (OVOC). O3 formation regimes were similar at different heights during both episodes and non-episodes, which was located either in volatile organic compounds (VOCs) sensitive regime or in transition regime and more sensitive to VOCs. Diurnally, photochemical O3 formation typically remained in the VOCs sensitive regime during the morning and noon time, but in the transitional regime and more sensitive to VOCs in the afternoon at around 16:00 LT. The vertical and temporal O3 formation are most sensitive to AVOC and OVOC, which suggests that targeting VOCs, especially AVOC and OVOC, for control measures is more practical and feasible at the observation site. The vertical temporal analysis of O3 formation mechanisms near the ground surface in this study provides critical foundational knowledge for formulating effective short-term emergency and long-term strategies to combat O3 pollution in the PRD region of China. [ABSTRACT FROM AUTHOR]

While gemfibrozil and fenofibrate are prescribed for anti-dyslipidemia treatment, a rational basis for the use of these drugs for treatment of dyslipidemia with concurrent metabolic syndrome has not been established. In this study, wild-type and Pparα-null mice were fed gemfibrozil- or fenofibrate-containing diets for 14 days. Urine output (24 h) was monitored, and urine, serum, and liver and kidney tissues were subjected to toxicity assessment. A 2-month challenge followed by a 2-week wash-out was performed for gemfibrozil to determine urine output and the potential toxicity. A therapeutically equivalent dose of gemfibrozil was more effective than fenofibrate in increasing urine output. This regulatory effect was not observed in Pparα-null mice. In contrast, hepatomegaly induced by fenofibrate was more pronounced than that of gemfibrozil. No significant toxicity was observed in liver or kidney in the 2-month treatment with gemfibrozil. These data demonstrated PPARα mediates the increased urine output by fibrates. Considering the relative action on hepatomegaly and the regulatory effect on urine output, gemfibrozil may be the preferable drug to increase urine output. These results revealed a new pharmacodynamic effect of clinically prescribed PPARα agonists and suggested the potential value of gemfibrozil in modification of blood pressure. Key words: gemfibrozil, urine output, PPARα, fenofibrate. Le gemfibrozil et le fenofibrate sont des medicaments prescrits pour traiter les dyslipidemies, mais les fondements de leur utilisation n'ont pas encore ete etablis dans le cas des dyslipidemies associees au syndrome metabolique. Dans cette etude, nous avons administre pendant 14 jours un regime alimentaire contenant du gemfibrozil ou du fenofibrate a des souris nulles Ppara et de type sauvage. Nous avons surveille le debit urinaire (sur 24 heures) et procede a des evaluations toxicologiques de l'urine, du serum et des tissus renal et hepatique. Afin de determiner le debit urinaire et une toxicite eventuelle, nous avons administre le gemfibrozil pendant une periode de provocation de 2 mois, suivie d'une periode de sevrage de 2 semaines. A une dose equivalente a celle qui est utilisee en therapeutique, le gemfibrozil etait plus efficace que le fenofibrate pour augmenter le debit urinaire. Nous n'avons pas observe cet effet regulateur chez la souris nulle Ppara. Inversement, l'hepatomegalie engendree avec le fenofibrate etait plus importante qu'avec le gemfibrozil. Nous n'avons observe aucune toxicite hepatique ou renale notable avec l'administration de gemfibrozil pendant 2 mois. Ces donnees montraient que le PPARα assure la mediation de l'augmentation du debit urinaire par les fibrates. Etant donne leurs effets respectifs sur l'hepatomegalie et la regulation du debit urinaire, le gemfibrozil pourrait etre un medicament plus avantageux que le fenofibrate pour augmenter le debit urinaire. Ces resultats ont revele un nouvel effet pharmacodynamique d'agonistes du PPARα prescrits en clinique et laissaient entrevoir la valeur potentielle du gemfibrozil pour modifier la tension arterielle. [Traduit par la Redaction] Mots-cles: gemfibrozil, debit urinaire, PPARα, fenofibrate., Introduction Metabolic syndrome (MS) is characterized by high serum triglyceride (TG), elevated blood pressure, abdominal obesity, elevated fasting plasma glucose, and low high-density lipoprotein-cholesterol (HDL-C). In the United States, the [...]

Current process-based research mainly uses box models to evaluate photochemical ozone production and destruction rates, and it is unclear to what extent the photochemical reaction mechanisms are elucidated. Here, we modified and improved a net photochemical ozone production rate (NPOPR, P (O 3) net) detection system based on the current dual-channel reaction chamber technique, which makes the instrument applicable to different ambient environments, and its various operating indicators were characterized, i.e., "airtightness", light transmittance, wall losses of the reaction and reference chambers, conversion rate of O 3 to NO 2 , air residence time, and performance of the reaction and reference chambers. The limits of detection of the NPOPR detection system were determined to be 0.07, 1.4, and 2.3 ppbv h -1 at sampling flow rates of 1.3, 3, and 5 L min -1 , respectively. We further applied the NPOPR detection system to field observations at an urban site in the Pearl River Delta (China). During the observation period, the maximum value of P (O 3) net was 34.1 ppbv h -1 , which was ∼ 0 ppbv h -1 at night within the system detection error and peaked at approximately noon local time. The daytime (from 06:00–18:00 LT) average value of P (O 3) net was 12.8 (± 5.5) ppbv h -1. We investigated the detailed photochemical O 3 formation mechanism in the reaction and reference chambers of the NPOPR detection system using a zero-dimensional box model. We found that the photochemical reactions in the reaction chamber were very close to those in ambient air, but there was not zero chemistry in the reference chamber because the reaction related to the production and destruction of RO 2 (= HO 2 + RO 2) continued in the reference chamber, which led to a small amount of P (O 3) net. Therefore, the P (O 3) net measured here can be regarded as the lower limit of the real P (O 3) net in the atmosphere; however, the measured P (O 3) net was still ∼ 7.5 to 9.3 ppbv h -1 higher than the modeled P (O 3) net value depending on different modeling methods, which may be due to the inaccurate estimation of HO 2 / RO 2 radicals in the modeling study. Short-lived intermediate measurements coupled with direct P (O 3) net measurements are needed in the future to better understand O 3 photochemistry. Our results show that the NPOPR detection system can achieve high temporal resolution and continuous field observations, which helps us to better understand photochemical O 3 formation and provides a key scientific basis for continuous improvement of air quality in China. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptors (PPARs) have been suggested to play crucial roles in the pathology of NAFLD with a vague understanding of the underlying mechanism. Here, we integrated large-scale literature data and clinical data to explore the potential role of the PPAR-APOA1 signaling pathway in the pathology of NAFLD. First, the signaling pathway connecting PPARs, APOA1, and NAFLD was constructed. Then, we employed clinical data to explore the association between APOA1 levels and NAFLD. In addition, we built the APOA1-driven pathway analysis to explore the potential mechanism of the APOA1-NAFLD association. Pathway analysis showed that APOA1 serves as a hubprotein connecting PPARs and NAFLD through a beneficial modulation of 16 out of 21 NAFLD upstream regulators. Each relationship within the composed pathway was supported by results from multiple previous studies. Clinical data analysis showed that an increase of APOA1 level was associated with a significantly decreased NAFLD prevalence ( χ 2 = 292.109 ; P < 0.001). When other confounding factors were adjusted, serum APOA1 level was shown as an independent risk factor for the prevalence of NAFLD (P value<.0001; OR = 0.562). Our results suggested that the three PPARs (PPARA, PPARD, and PPARG) might promote the expression and molecular transportation of APOA1 to form a PPAR-APOA1 signaling pathway that demonstrated a beneficial role in the pathogenesis of NAFLD. [ABSTRACT FROM AUTHOR]

Aiming Liu,2,* Yin Jiang,2 Dandan Chen,1 Binbin Li,3 Can Yao,3 Rongchang Chen,1 Fei Shi31Key Laboratory of Shenzhen Respiratory Diseases, Institute of Shenzhen Respiratory Diseases, Shenzhen People's Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, Guangdong, People's Republic of China; 2Shenzhen National Climate Observatory, Meteorological Bureau of Shenzhen Municipality, Shenzhen Key Laboratory of Severe Weather in South China, Shenzhen, Guangdong, People's Republic of China; 3Emergency Department, Institute of Shenzhen Respiratory Diseases, Shenzhen People's Hospital (The First Affiliated Hospital of Southern University of Science and Technology, The Second Clinical Medical College of Jinan University), Shenzhen, Guangdong, People's Republic of China*These authors contributed equally to this workCorrespondence: Rongchang Chen; Fei Shi Email [email protected] ; [email protected] Background: Reversible airflow obstruction (RO) and fixed airflow obstruction (FO) are two important clinical phenotypes of asthma. However, the relationship between air pollutant exposure and exacerbation of the two phenotypes is unknown. Objective: To study the effects of air pollutant exposure on exacerbation severity in asthma patients with or without FO. Methods: A total of 197 severe asthma patients were enrolled, and divided into two groups: the FO group (n=81) and the RO group (n=116). We collected the demographic data, laboratory parameters, pulmonary function test parameters, and the daily average concentrations of different air particles in Shenzhen on the different lag days of each subject. The receiver operating characteristic (ROC) curve was used to identify the effects of major air pollutants on the severity of asthma patients with RO. Results: Compared with the RO group, the FO group had fewer women, lower body mass index (BMI), longer disease duration, higher smoking history rate, allergic family history rate, FeNO level, and lower levels of large airway parameters. The median exposure levels of PM10 and PM2.5 in the severe RO subgroup were both higher than those in the mild-to-moderate RO subgroup on Lag0, 1 and 3, and the median exposure level of PM1 on Lag0 in the severe RO subgroup was significantly higher than that in the mild-to-moderate RO subgroup. Logistic regression modeling indicated exposure to PM2.5 and PM1.0 on Lag0, and PM10 on Lag0-2 were the independent risk factors for hospital admissions for asthma patients with RO. By performing an ROC curve analysis, PM2.5 on Lag0 (AUC = 0.645, p = 0.027) provided a best performance to predict severe asthma exacerbations with RO, with a sensitivity of 36.0% and a specificity of 91.2%. Conclusion: Short-term exposure to PM10, PM2.5 and PM1 may play a role in exacerbation severity among asthma patients with RO. [ABSTRACT FROM AUTHOR]