Lymphangiogenesis contributes to exercise-induced physiological cardiac growth

Background:Promoting cardiac lymphangiogenesis exerts beneficial effects for the heart.Exercise can induce physiological cardiac growth with cardiomyocyte hypertrophy and increased proliferation markers in cardiomyocytes.However,it remains unclear whether and how lymphangiogenesis contributes to exercise-induced physiological cardiac growth.We aimed to investigate the role and mechanism of lymphangiogenesis in exercise-induced physiological cardiac growth.Methods:Adult C57 BL6/J mice were subjected to 3 weeks of swimming exercise to induce physiological cardiac growth.Oral treatment with vascular endothelial growth factor receptor 3(VEGFR3) inhibitor SAR1 3 1 675 was used to investigate whether cardiac lymphangiogenesis was required for exercise-induced physiological cardiac growth by VEGFR3 activation.Furthermore,human dermal lymphatic endothelial cell(LEC)-conditioned medium was collected to culture isolated neonatal rat cardiomyocytes to determine whether and how LECs could influence cardiomyocyte proliferation and hypertrophy.Results:Swimming exercise induced physiological cardiac growth accompanied by a remarkable increase of cardiac lymphangiogenesis as evidenced by increased density of lymphatic vessel endothelial hyaluronic acid receptor 1-positive lymphatic vessels in the heart and upregulated LYVE-1 and Podoplanin expressions levels.VEGFR3 was upregulated in the exercised heart,while VEGFR3 inhibitor SAR131675 attenuated exercise-induced physiological cardiac growth as evidenced by blunted myocardial hypertrophy and reduced proliferation marker Ki67 in cardiomyocytes,which was correlated with reduced lymphatic vessel density and downregulated LYVE-1 and Podoplanin in the heart upon exercise.Furthermore,LEC-conditioned medium promoted both hypertrophy and proliferation of cardiomyocytes and contained higher levels of insulinlike growth factor-1 and the extracellular protein Reelin,while LEC-conditioned medium from LECs treated with SAR131675 blocked these effects.Functional rescue assays further demonstrated that protein kinase B(AKT) activation,as well as reduced CCAAT enhancer-binding protein beta(C/EBPβ) and increased CBP/p300-interacting transactivators with E(glutamic acid)/D(aspartic acid)-rich-carboxylterminal domain 4(CITED4),contributed to the promotive effect of LEC-conditioned medium on cardiomyocyte hypertrophy and proliferation.Conclusion:Our findings reveal that cardiac lymphangiogenesis is required for exercise-induced physiological cardiac growth by VEGFR3 activation,and they indicate that LEC-conditioned medium promotes both physiological hypertrophy and proliferation of cardiomyocytes through AKT activation and the C/EBPβ-CITED4 axis.These results highlight the essential roles of cardiac lymphangiogenesis in exercise-induced physiological cardiac growth.

Comprehensive understanding on sources of high levels of fine particulate nitro-aromatic compounds at a coastal rural area in northern China

Nitro-aromatic compounds(NACs)are among the major components of brown carbon(BrC)in the atmosphere,causing negative impacts on regional climate,air quality,and ecological health.Due to the extensive origins,it is still a challenge to figure out the contributions and originating regions for different sources of atmospheric NACs.Here,field observations on fine particulate NACs were conducted at a coastal rural area in Qingdao,China in the winter of 2018 and 2019.The mean total concentrations of fine particulate nitro-aromatic compounds were 125.0±89.5 and 27.7±21.1 ng/m^(3)in the winter of 2018 and 2019,respectively.Among the measured eleven NACs,nitrophenols and nitrocatechols were the most abundant species.Variation characteristics and correlation analysis showed that humidity and anthropogenic primary emissions had significant influences on the NAC abundances.In this study,two tracing methods of the improved spatial concentration weighted trajectory(SCWT)model and the receptor model of positive matrix factorization(PMF)were combined to comprehensively understand the origins of NACs in fine particles at coastal Qingdao.Four major sources were identified,including coal combustion,biomass burning,vehicle exhaust,and secondary formation.Surprisingly,coal combustion was responsible for about half of the observed nitro-aromatic compounds,followed by biomass burning(~30%).The results by SCWT demonstrated that the coal combustion dominated NACs mainly originated from the Shandong peninsula and the areas to the north and southwest,while those dominated by biomass burning primarily came from local Qingdao and the areas to the west.

Variation characteristics of atmospheric methane and carbon dioxide in summertime at a coastal site in the South China Sea

Methane(CH_(4))and carbon dioxide(CO_(2))are the two most important greenhouse gases(GHGs).To examine the variation characteristics of CH_(4)and CO_(2)in the coastal South China Sea,atmospheric CH_(4)and CO_(2)measurements were performed in Bohe(BH),Guangdong,China,in summer 2021.By using an adaptive data analysis method,the diurnal patterns of CH_(4)and CO_(2)were clearly extracted and analysed in relation to the sea breeze(SB)and land breeze(LB),respectively.The average concentrations of CH_(4)and CO_(2)were 1876.91±31.13 ppb and 407.99±4.24 ppm during SB,and 1988.12±109.92 ppb and 421.54±14.89 ppm during LB,respectively.The values of CH_(4)and CO_(2)during SB basically coincided with the values and trends of marine background sites,showing that the BH station could serve as an ideal site for background GHG monitoring and dynamic analysis.The extracted diurnal variations in CH_(4)and CO_(2)showed sunrise high and sunset low patterns(with peaks at 5:00–7:00)during LB but mid-morning high and evening low patterns(with peaks at 9:00)during SB.The diurnal amplitude changes in both CH_(4)and CO_(2)during LB were almost two to three times those during SB.Wind direction significantly modulated the diurnal variations in CH_(4)and CO_(2).The results in this study provide a new way to examine the variations in GHGs on different timescales and can also help us gain a better understanding of GHG sources and distributions in the South China Sea.

Roles of SO_2 oxidation in new particle formation events

The oxidation of SO2 is commonly regarded as a major driver for new particle formation（NPF） in the atmosphere. In this study, we explored the connection between measured mixing ratio of SO2 and observed long-term（duration 〉 3 hr） and short-term（duration〈 1.5 hr） NPF events at a semi-urban site in Toronto. Apparent NPF rates（J30） showed a moderate correlation with the concentration of sulfuric acid（[H2SO4]） calculated from the measured mixing ratio of SO2 in long-term NPF events and some short-term NPF events（Category I）（R^2= 0.66）. The exponent in the fitting line of J30~ [H2SO4]nin these events was1.6. It was also found that SO2 mixing ratios varied a lot during long-term NPF events,leading to a significant variation of new particle counts. In the SO2-unexplained short-term NPF events（Category II）, analysis showed that new particles were formed aloft and then mixed down to the ground level. Further calculation results showed that sulfuric acid oxidized from SO2 probably made a negligible contribution to the growth of 〉 10 nm new particles.