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INTRODUCTION: Vitexin is a natural flavonoid compound extracted from Vitex leaves or seeds, exhibiting various pharmacological activities including anticancer, antihypertensive, anti-inflammatory, and spasmolytic effects. However, its protective effects on hypertensive nephropathy (HN) and the underlying mechanisms remain unclear. METHODS: Spontaneous hypertension rats were fed a high-sugar and high-fat diet for 8 weeks to induce the disease HN model. From the 5th week, the rats were administered vitexin via gavage. Blood pressure was measured bi-weekly using the tail-cuff method. Histopathological changes were assessed using HE staining, and biochemical analyses were performed to evaluate the effects of vitexin on HN rats. The underlying mechanisms of vitexin treatment were investigated through western blotting. RESULTS: The data demonstrated that vitexin significantly lowered systolic, diastolic, and mean arterial pressures, and ameliorated histopathological changes in HN rats. Biochemical analyses revealed that vitexin reduced the levels of creatinine (Cr), blood urea nitrogen (BUN), total cholesterol (TC), triglycerides (TG), total protein (TP), low-density lipoprotein cholesterol (LDL-C), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), malondialdehyde (MDA), and advanced glycation end products (AGEs), while increasing the levels of albumin (ALB) and superoxide dismutase (SOD). Western blotting results indicated that vitexin treatment decreased the expression of TNF-α, IL-6, and nuclear factor kappa-B (NF-κB), while increasing the expression of SOD. CONCLUSION: The findings of this study suggest that vitexin exerts protective effects against HN, providing pharmacological evidence for its potential use in HN treatment.
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Objective: Over the past few decades, the development of anti-cancer drugs in China has made outstanding achievements based on the support of national policies. To assess the progress of non-small cell lung cancer (NSCLC) drugs, we conducted a statistical analysis of clinical trials of drugs targeting NSCLC in China from 2005 to 2023. Methods: We downloaded, screened and analysed the data from three official websites, the Centre for Drug Evaluation of China National Medical Products Administration website (NMPA), ClinicalTrials.gov and the Chinese Clinical Trial Registry (ChiCTR). Results: From January 1, 2005 to April 15, 2023, a total of 1,357 drug clinical trials that met the standards were included, and the number of registered drug clinical trials has been increasing year by year, reaching the maximum of 199 in 2021. Among them, the maximum of 462 items (34.05%) in phase II clinical trials, followed by 333 (24.54%) in phase III clinical trials, and 139 (10.24%) in phase IV clinical trials. In all drug clinical trials, industry sponsored trials (ISTs) have 722 items (53.21%), which are higher than investigator-initiated trials (IITs). The clinical trials of chemical drugs have a maximum of 723 items (53.28%), while biopharmaceuticals have grown rapidly in the past 10 years, with a total of 374 (27.56%), and 48.19% of the drug clinical trials of combined medication. In addition, the geographical distribution of the leading units and participating units of Chinese drug clinical trials are uneven, and economic regions such as Beijing, Shanghai, Jiangsu are obviously ahead of other regions. Conclusion: From 2005 to 2023, the clinical trials of registered drugs for the treatment of NSCLC increased rapidly. Among them, due to the development of immunotherapy, the clinical trials of biopharmaceuticals and drugs for combined medication are growing most rapidly, while the exploration of the original drugs is a little far from enough. Our research provides a direction for the future drug clinical trials of NSCLC, laying foundation for further extending the survival rate of patients with NSCLC.
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Purpose: Ginsenoside Rb1 (Rb1), one of the crucial bioactive constituents in Panax ginseng C. A. Mey., possesses anti-type 2 diabetes mellitus (T2DM) property. Nevertheless, the precise mechanism, particularly the impact of Rb1 on hepatic glycogen production, a crucial process in the advancement of T2DM, remains poorly understood. 15-hydroxyprostaglandin dehydrogenase (15-PGDH) is responsible for prostaglandin E2 (PGE2) inactivation. A recent study has reported that inhibition of 15-PGDH promoted hepatic glycogen synthesis and improved T2DM. Therefore, herein, we aimed to investigate whether Rb1 ameliorated T2DM through 15-PGDH/PGE2-regulated hepatic glycogen synthesis. Methods: By combining streptozotocin with a high-fat diet, we successfully established a mouse model for T2DM. Afterward, these mice were administered Rb1 or metformin for 8 weeks. An insulin-resistant cell model was established by incubating LO2 cells with palmitic acid. Liver glycogen and PGE2 levels, the expression levels of 15-PGDH, serine/threonine kinase AKT (AKT), and glycogen synthase kinase 3 beta (GSK3ß) were measured. Molecular docking was used to predict the binding affinity between 15-PGDH and Rb1. Results: Rb1 administration increased the phosphorylation levels of AKT and GSK3ß to enhance glycogen synthesis in the liver of T2DM mice. Molecular docking indicated that Rb1 had a high affinity for 15-PGDH. Moreover, Rb1 treatment resulted in the suppression of elevated 15-PGDH levels and the elevation of decreased PGE2 levels in the liver of T2DM mice. Furthermore, in vitro experiments showed that Rb1 administration might enhance glycogen production by modulating the 15-PGDH/PGE2/PGE2 receptor EP4 pathway. Conclusion: Our findings indicate that Rb1 may enhance liver glycogen production through a 15-PGDH-dependent pathway to ameliorate T2DM, thereby offering a new explanation for the positive impact of Rb1 on T2DM and supporting its potential as an effective therapeutic approach for T2DM.
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Type 2 diabetes mellitus (T2DM) is a rapidly growing epidemic that results in increased morbidity, mortality, and soaring medical costs. Prostaglandin E2 (PGE2), a vital lipid mediator, has been reported to protect against hepatic steatosis, inflammation, endoplasmic reticulum (ER) stress, and insulin resistance, indicating its potential therapeutic role in T2DM. PGE2 can be degraded by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). SW033291, an inhibitor of 15-PGDH, has been reported to increase PGE2 levels, however, the effect of SW033291 in T2DM remains to be explored. This study aims to evaluate whether SW033291 protects against T2DM and explore its potential mechanisms. A T2DM mouse model was established through high-fat diet/streptozotocin injection, while palmitic acid-treated mouse primary hepatocytes were used as insulin-resistant cell models. SW033291 treatment reduced body weight, fat weight, fasting blood glucose, and improved impaired glucose tolerance and insulin resistance in T2DM mice. More importantly, SW033291 alleviated steatosis, inflammation, and ER stress in the liver of T2DM mice. Mechanistically, SW033291 decreased the expressions of SREBP-1c and ACC1, and increased the expression of PPARα in T2DM mice. Additionally, SW033291 inhibited NF-κB and eIF2α/CHOP signaling in T2DM mice. Further, we showed that the protective effects of SW033291 on the above-mentioned pathophysiological processes could be hindered by inhibition of the PGE2 receptor EP4. Overall, our study reveals a novel role of SW033291 in alleviating T2DM and suggests its potential as a new therapeutic strategy for T2DM.
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Diabetes Mellitus Tipo 2 , Hígado Graso , Resistencia a la Insulina , Ratones , Animales , Dinoprostona/metabolismo , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo de los Lípidos , Resistencia a la Insulina/fisiología , Hígado/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Hígado Graso/metabolismoRESUMEN
Type 2 diabetes mellitus (T2DM) is associated with high rates of morbidity and mortality worldwide. Prostaglandin E2 (PGE2) is a lipid signaling molecule that can ameliorate the symptoms of some metabolic diseases, including T2DM, and improve tissue repair and regeneration. Although SW033291 can increase PGE2 levels through its action as a small molecule inhibitor of the PGE2-degrading enzyme 15-hydroxyprostaglandin dehydrogenase, its effects on T2DM remain unclear. In the present study, we evaluated whether SW033291 treatment exerts a protective effect against T2DM and explored the underlying mechanisms. A T2DM mouse model was established using a high-fat diet combined with streptozotocin treatment. Palmitic acid-treated LO2 cells were used as an insulin-resistant cell model. SW033291 treatment reduced body weight and fasting blood glucose levels as well as serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels in vivo. In addition to ameliorating glucose and insulin tolerance, SW033291 treatment reversed the T2DM-induced decrease in glycogen synthesis and increase in gluconeogenesis in the liver. Furthermore, SW033291 administration increased hepatic glycogen synthase kinase 3 beta (GSK3ß) phosphorylation levels to promote glycogen synthesis. SW033291 treatment also inhibited gluconeogenesis by upregulating AKT serine/threonine kinase (AKT) and forkhead box O1 (FOXO1) phosphorylation and reducing glucose-6-phosphatase and phosphoenolpyruvate carboxykinase 1 expression in the livers of T2DM model mice. Additionally, SW033291 treatment improved abnormal hepatic glucose metabolism through the PGE2-EP4 receptor-AKT-GSK3ß/FOXO1 signaling pathway in vitro. These results suggest a novel role of SW033291 in improving T2DM and support its potential as a novel therapeutic agent.
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Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Animales , Ratones , Colesterol/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Dinoprostona/metabolismo , Modelos Animales de Enfermedad , Glucosa/metabolismo , Glucógeno/metabolismo , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Hígado/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Insulina/metabolismoRESUMEN
Atherosclerosis, a trigger of cardiovascular disease, poses grave threats to human health. Although atherosclerosis depends on lipid accumulation and vascular wall inflammation, abnormal phenotypic regulation of macrophages is considered the pathological basis of atherosclerosis. Macrophage polarization mainly refers to the transformation of macrophages into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, which has recently become a much-discussed topic. Increasing evidence has shown that M2 macrophage polarization can alleviate atherosclerosis progression. PGE2 is a bioactive lipid that has been observed to be elevated in atherosclerosis and to play a pro-inflammatory role, yet recent studies have reported that PGE2 promotes anti-inflammatory M2 macrophage polarization and mitigates atherosclerosis progression. However, the mechanisms by which PGE2 acts remain unclear. This review summarizes current knowledge of PGE2 and macrophages in atherosclerosis. Additionally, we discuss potential PGE2 mechanisms of macrophage polarization, including CREB, NF-κB, and STAT signaling pathways, which may provide important therapeutic strategies based on targeting PGE2 pathways to modulate macrophage polarization for atherosclerosis treatment.
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Aterosclerosis , Dinoprostona , Humanos , Dinoprostona/metabolismo , Aterosclerosis/metabolismo , Transducción de Señal , FN-kappa B/metabolismo , Macrófagos/metabolismo , Activación de MacrófagosRESUMEN
The COVID-19 epidemic has exerted significant impacts on human health, social and economic activities, air quality and atmospheric chemistry, and potentially on climate change. In this study, an online coupled regional climate-chemistry-aerosol model (RIEMS-Chem) was applied to explore the direct, indirect, and feedback effects of anthropogenic aerosols on radiation, boundary layer meteorology, and fine particulate matter during the COVID-19 lockdown period from 23 January to 8 April 2020 over China. Model performance was validated against a variety of observations for meteorological variables, PM2.5 and its chemical components, aerosol optical properties, as well as shortwave radiation flux, which demonstrated that RIEMS-Chem was able to reproduce the spatial distribution and temporal variation of the above variables reasonably well. During the study period, direct radiative effect (DRE) of anthropogenic aerosols was stronger than indirect radiative effect (IRE) in most regions north of the Yangtze River, whereas IRE dominated over DRE in the Yangtze River regions and South China. In North China, DRE induced larger changes in meteorology and PM2.5 than those induced by IRE, whereas in South China, the changes by IRE were remarkably larger than those by DRE. Emission reduction alone during the COVID-19 lockdown reduced PM2.5 concentration by approximately 32 % on average over East China. As a result, DRE at the surface was weakened by 15 %, whereas IRE changed little over East China, leading to a decrease in total radiative effect (TRE) by approximately 7 % in terms of domain average. The DRE-induced changes in meteorology and PM2.5 were weakened due to emission reduction, whereas the IRE-induced changes were almost the same between the cases with and without emission reductions. By aerosol radiative and feedback effects, the COVID-19 emission reductions resulted in 0.06 °C and 0.04 °C surface warming, 1.6 and 4.0 µg m-3 PM2.5 decrease, 0.4 and 1.3 mm precipitation increase during the lockdown period in 2020 in terms of domain average over North China and South China, respectively, whereas the lockdown caused negligible changes on average over East Asia.
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Contaminantes Atmosféricos , Contaminación del Aire , COVID-19 , Humanos , Material Particulado/análisis , Contaminantes Atmosféricos/análisis , Meteorología , Retroalimentación , Monitoreo del Ambiente/métodos , Control de Enfermedades Transmisibles , Aerosoles y Gotitas Respiratorias , Contaminación del Aire/análisis , China/epidemiologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Fufang-zhenzhu-tiaozhi formula (FTZ) is a patented preparation of traditional Chinese medicine that has been used to treat hyperglycemia and hyperlipidemia in the clinic for almost 10 years. Our previous study had demonstrated that FTZ can protect islet ß cell injury in vitro. However, the efficacy of FTZ on ß cell regeneration in vivo and the involved anti-diabetic mechanism remains unknown. AIM OF THE STUDY: We aim to investigate the effects of FTZ as a good remedy for islet protection and ß cell regeneration, and to reveal the underlying mechanism. MATERIALS AND METHODS: C57BL/6 mice were fed with high-fat diet for 3 weeks and then intraperitoneally injected with streptozotocin (90 mg/kg/d × 1 d) to establish type 2 diabetes (T2D) models. Mice in each group were divided into three batches that sacrificed after 3, 7 and 28 days of FTZ administration. Body weight, blood glucose, and oral glucose tolerance test were measured at indicated time points. Fasting insulin was determined by enzyme-linked immunosorbent assay (ELISA) kit. Neonatal ß cell was assessed by insulin & PCNA double immunofluorescence staining, and the underlying mechanisms related to ß cell regeneration were further performed by hematoxylin-eosin staining, insulin & glucagon double immunofluorescence staining and Western blot. RESULTS: FTZ and metformin can significantly help with the symptoms of DM, such as alleviating weight loss, reducing blood glucose, improving the level of insulin in vivo, and relieving insulin resistance, suggesting FTZ and metformin treatment maintained the normal morphological function of islet. Notably, ß cell regeneration, which is indicated by insulin and PCNA double-positive cells, was promoted by FTZ, whereas few neonatal ß cells were observed in metformin group. Hematoxylin-eosin staining, and its quantification results showed that FTZ effectively prevented the invasion of inflammatory cells into the islets in diabetic mice. Most ß cells in the islets of diabetic model mice were devoid, and the islets were almost all α cells, while the diabetic mice administered FTZ could still maintain about half of the ß cells in the islet. Furthermore, FTZ upregulated the expression of critical transcription factors during ß cell development and maturation (such as PDX-1, MAFA and NGN3) in diabetic mice. CONCLUSIONS: FTZ can alleviate diabetes symptoms and promote ß cell regeneration in diabetic mice. Moreover, FTZ promotes ß cell regeneration by preserving islet (resisting inflammatory cells invading islets), maintaining the number of ß cells in islets, and increasing the expression of PDX-1, MAFA and NGN3.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Islotes Pancreáticos , Metformina , Ratones , Animales , Glucemia/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Experimental/metabolismo , Eosina Amarillenta-(YS)/metabolismo , Eosina Amarillenta-(YS)/farmacología , Hematoxilina/metabolismo , Hematoxilina/farmacología , Antígeno Nuclear de Célula en Proliferación/metabolismo , Ratones Endogámicos C57BL , Insulina , Regeneración , Metformina/farmacologíaRESUMEN
A Regional Air Quality Model System (named RAQMS) coupled with a developed dust model driven by WRF was applied to synthetically investigate the emission, transport, deposition, budget, and chemical and radiative effects of mineral dust during the severe dust storm periods of 10-31 March 2021. Model results were validated against a variety of ground, vertical and satellite observations, which demonstrated a generally good model ability in reproducing meteorological variables, particulate matter and compositions, and aerosol optical properties. The first dust storm (DS1), which was the severest one since 2010 was originated from the Gobi Desert in southern Mongolia on 14 March, with the dust emission flux reaching 2785 µg m-2 s-1 and the maximum dust concentration exceeding 18,000 µg m-3 in the dust deflation region. This dust storm resulted in remarkably high hourly PM10 observations up to 7506 µg m-3, 1887 µg m-3, and 2704 µg m-3 in Beijing, Tianjin, and Shijiazhuang on 15 March, respectively, and led to a maximum decrease in surface shortwave radiation up to 313.4 W m-2 (72 %) in Beijing. The second dust storm (DS2) broke out in the deserts of eastern Mongolia, with lower dust emission than the first one. The extinction of shortwave radiation by dust aerosols led to a reduction in photolysis rate and consequently decreases in O3 and secondary aerosol concentrations over the North China Plain (NCP), whereas total sulfate and nitrate concentrations consistently increased due to heterogeneous reactions on dust surfaces over the middle reaches of the Yellow River and the NCP region during DS1. Sulfate and nitrate formation through heterogeneous reactions were enhanced in the dust backflow on 16-17 March by approximately 18 % and 24 % on average in the NCP. Heterogeneous reactions and photolysis rate reduction by mineral dust jointly led to average changes in sulfate, nitrate, ammonium, and secondary organic aerosol (SOA) concentrations by 13.0 %, 13.5 %, -12.3 %, and -4.4 %, respectively, in the NCP region during DS1, larger than the changes in the Yangtze River Delta (YRD). The maximum dry deposition settled in the 7-11 µm size range in downwind land and ocean areas, while wet deposition peaked in the 4.7-7 µm size range in the entire domain. Wet deposition was approximately twice the dry deposition over mainland China except for dust source regions. During 10-31 March, the total dust emission, dry and wet depositions were estimated to be 31.4 Tg, 13.78 Tg and 4.75 Tg, respectively, with remaining 12.87 Tg of dust aerosols (41 % of the dust emission) suspending in the atmosphere or transporting to other continents and oceans.
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Contaminantes Atmosféricos , Compuestos de Amonio , Contaminantes Atmosféricos/análisis , Nitratos/análisis , Monitoreo del Ambiente/métodos , Polvo/análisis , Aerosoles/análisis , Material Particulado/análisis , Asia Oriental , Minerales , China , Sulfatos/análisis , Estaciones del AñoRESUMEN
In the face of the health challenges caused by the COVID-19 pandemic, healing and therapeutic design (HTD) as interventions can help with improving people's health. It is considered to have great potential to promote health in the forms of art, architecture, landscape, space, and environment. However, there are insufficient design approaches to address the challenges during the HTD process. An increased number of studies have shown that emerging information modeling (IM) such as building information modeling (BIM), landscape information modeling (LIM), and city information modeling (CIM) coupled with blockchain (BC) functionalities have the potential to enhance designers' HTD by considering important design elements, namely design variables, design knowledge, and design decision. It can also address challenges during the design process, such as design changes, conflicts in design requirements, the lack of design evaluation tools and frameworks, and incomplete design information. Therefore, this paper aims to develop a conceptual BC enhanced IM for HTD (BC-HTD) framework that addresses the challenges in the HTD and promotes health and well-being. The structure of BC-HTD framework is twofold: (1) a conceptual high-level framework comprising three levels: user; system; and information, (2) a conceptual low-level framework of detailed content at the system level, which has been constructed using a mixed quantitative and qualitative method of literature analysis, and validated via a pre-interview questionnaire survey and follow-up interviews with industry experts and academics. This paper analyzes the process of BC enhanced HTD and the knowledge management of HTD to aid design decisions in managing design information. This paper is the first attempt to apply the advantages of BC enabled IM to enhance the HTD process. The results of this study can foster and propel new research pathways and knowledge on the value of design in the form of non-fungible token (NFT) based on the extended advantages of BC in the field of design, which can fully mobilize the healing and therapeutic behaviors of designers and the advantage potential of HTD to promote health, and realize the vision of Health Metaverse in the context of sustainable development.
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Cadena de Bloques , COVID-19 , COVID-19/epidemiología , Promoción de la Salud , Humanos , Pandemias/prevención & control , Desarrollo SostenibleRESUMEN
A regional air quality model system (RAQMS) driven by the Weather Research and Forecasting model (WRF) is applied to investigate the distribution and evolution of mineral dust and anthropogenic aerosols over China in April 2020, when air quality was improved due to reduced human activity during the COVID-19 epidemic, whereas dust storms began to attack China and deteriorated air quality. A dust deflation model was developed and improved mineral dust prediction. Model validation demonstrated that RAQMS was able to reproduce PM10, PM2.5 and aerosol components reasonably well. China suffered from three dust events in April 2020, with the maximum hourly PM10 concentrations exceeding 700 µg m-3 in downwind cities over the North China Plain (NCP). Mineral dust dominated PM10 mass (>80%) over the Gobi deserts in north and west China, while it comprised approximately 30-50% of PM10 over wide areas of east China. The domain and monthly mean dust mass fractions in PM10 were estimated to be 47% and 43% over the North China Plain and east China, respectively. On average, mineral dust contributed up to 22% and 21% of PM2.5 mass over the North China Plain and east China in April 2020, respectively. Sulfate and nitrate produced by heterogeneous chemical reactions on dust surface accounted for approximately 9% and 13% of secondary inorganic aerosols (SIA) concentration over the North China Plain and east China, respectively. The results from this study demonstrated that mineral dust made an important contribution to particulate matter mass during the COVID-19 epidemic in spring 2020 over China.
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Various precursor emissions and chemical mechanisms for secondary organic aerosol (SOA) formation were incorporated into a regional air quality model system (RAQMS) and applied to investigate the distribution, composition, and source contribution of SOA over east China in summer 2018. Model comparison against a variety of observations at a national scale demonstrated that the model was able to reasonably reproduce meteorological variables, O3 and PM2.5 concentrations, and the model simulated SOA concentration generally agreed with observations, with the overall NMB of 7.0% and R of 0.4 in 10 cities over east China. The simulated period-mean SOA concentrations of 4-15 µg m-3 were mainly distributed over the North China Plain (NCP), the middle and lower reaches of the Yangtze River and Chongqing district. SOA dominated organic aerosol (OA) over China in summertime (90%). The percentage contributions to SOA from ASOA (SOA produced from anthropogenic volatile organic compounds (AVOC)), BSOA (SOA produced from biogenic volatile organic compounds (BVOC)), DSOA (SOA produced from aqueous uptake of glyoxal and methylglyoxal) and S/I-SOA (SOA produced from semi-volatile and intermediate volatile organic compounds) were estimated to be 48.3%, 28.6%, 14.3%, and 8.8% respectively, over east China in summertime. In terms of domain and period average, ASOA contributed most to SOA (59%) in north China, while BSOA contributed most to SOA (37.3%) in northeast China. The percentage contribution of DSOA to SOA reached 21.5% in southwest China. S/I-SOA accounted for approximately 10% of SOA in most areas of east China. This study reveals that while AVOC dominates SOA formation on average over east China, the SOA source contributions differ considerably in different regions of China. BVOC makes the same contribution to SOA formation as AVOC in northeast China and southwest China, where forest coverage and BVOC emission are higher and anthropogenic emissions are relatively low, highlighting the significant role of BVOC in summer SOA formation in China.
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Contaminantes Atmosféricos , Contaminación del Aire , Compuestos Orgánicos Volátiles , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , China , Compuestos Orgánicos Volátiles/análisisRESUMEN
Objective: This study aimed to assess the main components of Artemisia annua L. essential oil (AEO) and determine their effect on the proliferation and differentiation of RAW264.7 cells induced by receptor activator for nuclear factor-ligand (RANKL) in vitro. Then, we tried to explain part of the function of its possible mechanisms. Materials and Methods: Essential oil was extracted from Artemisia annua L. Osteoclasts were induced in vitro by RANKL in mouse RAW264.7 cells. The experimental group was treated with different concentrations of AEO, while the control group was not treated with AEO. CCK8 was used to detect osteoclast proliferation. The osteoclasts were stained with TRAP. Western blot was used to detect protein in the MAPK pathway and the NF-κB pathway after treatment with different concentrations of AEO. RT-PCR was used to determine the expression of osteoclast-related mRNA in cells. Results: The GC-MS analysis was used to obtain the main components of AEO, including camphor, borneol, camphor, borneol, terpinen-4-ol, p-cymene, eucalyptol, deoxyartemisinin, and artemisia ketone. The CCK8 results showed that the AEO volume ratio of 1 : 4000, 1 : 5000, and 1 : 6000 did not affect the proliferation of RAW264.7 cells. However, TRAP staining showed that AEO decreased osteoclast formation. Western blot results showed that the expression of protein TRAF6, p-p38, p-ERK, p-p65, and NFATc1 decreased in the MAPK pathway and the NF-κB pathway affected by AEO. Furthermore, RT-PCR results showed that the expression of osteoclast resorption-related mRNAs (MMP-9, DC-STAMP, TRAP, and CTSK) and osteoclast differentiation-related mRNAs (OSCAR, NFATc1, c-Src, and c-Fos) also decreased in the experimental group. Conclusions: AEO inhibits osteoclast differentiation in vitro, probably by reducing TRAF6 activation, acting on the MAPK pathway and NF-κB pathway, and inhibiting the expression of osteoclast-related genes.
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The North China Plain and the Yangtze River Delta are the two of the most heavily polluted regions in China. Observational studies revealed that 'explosive' PM2.5 mass concentration growths frequently occurred in the two regions. This study analyzed all the PM2.5 mass concentration growth processes from clean condition (i.e., <35⯵gâ¯m-3) to heavy pollution condition (i.e., >150⯵gâ¯m-3) in Beijing (BJ) and Shanghai (SH), two representative cities of the two regions, using hourly monitored PM2.5 concentrations during 2013-2016. 173 and 76 growth processes were identified in BJ and SH, respectively. PM2.5 rising rates (PMRR) and dynamic growth durations were calculated to illustrate the characteristics of the growth processes. Hourly particulate chemical composition data and meteorological data in BJ and SH were further analyzed. The 4-year averaged PMRR of PM2.5 total mass were similarly of 7.11⯱â¯9.82⯵gâ¯m-3 h-1 in BJ and 6.71⯱â¯6.89⯵gâ¯m-3 h-1 in SH. A decreasing trend was found for the PM2.5 growth processes in two cities from 2013 to 2016, reflecting the effectiveness of emission controls implemented in the past years. The contributions of particulate components to the PM2.5 total mass growth were different in BJ and SH. Average PMRR value of PM1 organic aerosols (OA), SO42-, NO3-, and NH4+ in BJ was 1.90, 0.95, 0.82, and 0.53⯵gâ¯m-3 h-1, respectively. Average PMRR of PM2.5 OA, SO42-, NO3-, and NH4+ in SH was 1.70, 1.18, 1.99 and 1.14⯵gâ¯m-3 h-1, respectively. Based on the contributions of different components, the PM2.5 mass concentration growth processes in BJ and SH were proposed to be classified into 'other components-dominant growth processes', 'all components-contributing growth processes', 'one or more explosive secondary components-dominant growth processes', and 'mixed-factor growth processes'. Potential source contribution function analysis and the meteorological condition analysis showed that source origins and prevailing wind for the two cities during different categories of growth processes had substantial difference. The important source areas included Hebei and Shandong for BJ, and Jiangsu and Anhui for SH. The dominant wind directions during growth processes were northeast, south and southwest in BJ, and were west to north in SH. The results suggested the contributing components, the prevailing wind conditions, and the formation processes were substantially different in the two cities, despite the similar PMRR of PM2.5 total mass during the growth processes between BJ and SH. Future research is needed to study the detailed formation mechanisms of the different PM2.5 mass concentration growth processes in the two cities.
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Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Material Particulado/análisis , Aerosoles/análisis , Contaminación del Aire/análisis , Contaminación del Aire/prevención & control , Beijing , China , Ciudades , Monitoreo del Ambiente/métodos , Contaminación Ambiental/análisis , VientoRESUMEN
Define the admixture additive processes X γ , H , α a 1 , a 2 , a 3 , a 4 ( t ) â a 1 B ( t 1 ) + a 2 W γ ( t 2 ) + a 3 B H ( t 3 ) + a 4 S α ( t 4 ) ∈ R , and the admixture multiplicative processes Y γ , H , α ( t ) â B ( t 1 ) â W γ ( t 2 ) â B H ( t 3 ) â S α ( t 4 ) ∈ R , where t = ( t 1 , t 2 , t 3 , t 4 ) ∈ R + 4 , a 1 , a 2 , a 3 , a 4 are finite constants, B ( t 1 ) is the standard Brownian motion, W γ ( t 2 ) is the fractional integrated Brownian motion with index parameter γ > - 1 / 2 , B H ( t 3 ) is the fractional Brownian motion with Hurst parameter H ∈ ( 0 , 1 ) , S α ( t 4 ) is the stable process with index α ∈ ( 0 , 2 ] , and they are independent of each other. The small deviation for X γ , H , α a 1 , a 2 , a 3 , a 4 ( t ) and the lower bound of small deviation for Y γ , H , α ( t ) are obtained. As an application, limit inf type LIL is given for X γ , H , α a 1 , a 2 , a 3 , a 4 ( t ) .
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Object recognition and modeling have classically been studied separately, but practically, they are two closely correlated aspects. In this paper, by exploring the interrelations, we propose a framework to address these two problems at the same time, which we call simultaneous recognition and modeling. Differing from traditional recognition process which consists of off-line object model learning and on-line recognition procedures, our method is solely online. Starting with an empty object database, we incrementally build up object models while at the same time using these models to identify newly observed object views. In the proposed framework, objects are modeled as view graphs and a probabilistic observation model is presented. Both the appearance and the spatial structure of the object are examined, and a formulation based on maximum likelihood estimation is developed. Joint object recognition and modeling are achieved by solving the optimization problem. To evaluate the framework, we have developed a method for simultaneously learning multiple 3-D object models directly from the cluttered indoor environment and tested it using several everyday scenes. Experimental results demonstrate that the framework can cope with the recognition and modeling problem together nicely.