Downregulation of HMGB1 carried by macrophage-derived extracellular vesicles delays atherosclerotic plaque formation through Caspase-11-dependent macrophage pyroptosis.

BACKGROUND: Macrophage-derived extracellular vesicle (macrophage-EV) is highly studied for its regulatory role in atherosclerosis (AS). Our current study tried to elucidate the possible role of macrophage-EV loaded with small interfering RNA against high-mobility group box 1 (siHMGB1) affecting atherosclerotic plaque formation. METHODS: In silico analysis was performed to find critical factors in mouse atherosclerotic plaque formation. EVs secreted by RAW 264.7 cells were collected by ultracentrifugation and characterized, followed by the preparation of macrophage-EV-loaded siHMGB1 (macrophage-EV/siHMGB1). ApoE-/- mice were used to construct an AS mouse model by a high-fat diet, followed by injection of macrophage-EV/siHMGB1 to assess the in vivo effect of macrophage-EV/siHMGB1 on AS mice. RAW264.7 cells were subjected to ox-LDL, LPS or macrophage-EV/siHMGB1 for analyzing the in vitro effect of macrophage-EV/siHMGB1 on macrophage pyrophosis and inflammation. RESULTS: In silico analysis found that HMGB1 was closely related to the development of AS. Macrophage-EV/siHMGB could inhibit the release of HMGB1 from macrophages to outside cells, and the reduced HMGB1 release could inhibit foam cell formation. Besides, macrophage-EV/siHMGB also inhibited the LPS-induced Caspase-11 activation, thus inhibiting macrophage pyroptosis and preventing atherosclerotic plaque formation. CONCLUSION: Our results proved that macrophage-EV/siHMGB could inhibit foam cell formation and suppress macrophage pyroptosis, finally preventing atherosclerotic plaque formation in AS mice.

Alirocumab effect on preventing periprocedural ischaemic events in coronary heart disease patients undergoing coronary stenting (APPEASE trial): study protocol of a multicentre, open-label, randomised controlled trial.

INTRODUCTION: Percutaneous coronary intervention (PCI)-related myocardial infarction (type 4a MI) and major periprocedural myocardial injury have been demonstrated leading to poor prognosis of patients with coronary heart disease (CHD) undergoing elective PCI and still remain high occurrence even after the therapy of dual antiplatelet agents and statins. Proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab has been shown to be effectively in reducing the risk of acute MI (AMI). However, the effect of alirocumab on preventing PCI-related MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI remains uncertain. METHODS AND ANALYSIS: Alirocumab effect on Preventing Periprocedural ischaemic Events in coronary heart diseAse patients undergoing coronary StEnting trial is a multicentre, open-label, randomised controlled trial aiming to determine whether alirocumab could reduce the incidence of type 4a MI or major periprocedural myocardial injury in patients with CHD undergoing elective PCI. In total, 422 non-AMI CHD patients planned to undergo elective PCI will be randomly assigned to receive standard pharmacotherapy of CHD (control group) or additional use of subcutaneous alirocumab 75 mg 1 day before procedure (alirocumab group). The primary outcome is type 4a MI or major periprocedural myocardial injury defined as high-sensitivity cardiac troponin elevating above 5×99 th percentile upper reference limit in 48 hours after PCI. Patients will continue receiving standard pharmacotherapy or additional biweekly subcutaneous alirocumab 75 mg for 3 months according to the initial randomisation group. We will follow up for 3 months and record all the major adverse cardiovascular events (MACEs). Incidence of PCI-related MI or major periprocedural myocardial injury, and MACE in 3 months after PCI will be compared between control group and alirocumab group. ETHICS AND DISSEMINATION: Ethics approval has been obtained from the Medical Ethics Committee of the Third Affiliated Hospital of Sun Yat-sen University with approval number: (2022)02-140-01. The results of this study will be reported through peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: ChiCTR2200063191.

Developing a novel framework to re-examine half a century of compound drought and heatwave events in mainland China.

Compound drought and heatwave events (CDHEs) are more devastating than single drought or heatwave events and have gained widespread attention. However, previous studies have not investigated the impacts of the precipitation attenuation effect (PAE) (i.e., the effect of previous precipitation on the dryness and wetness of the current system is attenuated) and event merging (EM) (i.e., merging two CDHEs with short intervals into a single event). Moreover, few studies have assessed short-term CDHEs within monthly scales and their variation characteristics under different background temperatures. Here we propose a novel framework for assessing CDHEs on a daily scale and considering the PAE and EM. We applied this framework to mainland China and investigated the spatiotemporal variation of the CDHE indicators (spatial extent (CDHEspa), frequency (CDHEfre), duration (CHHEdur), and severity (CDHEsev)) from 1968 to 2019. The results suggested that ignoring the PAE and EM led to significant changes in the spatial distribution and magnitude of the CDHE indicators. Daily-scale assessments allowed for monitoring the detailed evolution of CDHEs and facilitated the timely development of mitigation measures. Mainland China experienced frequent CDHEs from 1968 to 2019 (except for the southwestern part of Northwest China (NWC) and the western part of Southwest China (SWC)), whereas, hotspot areas of CDHEdur and CDHEsev had a patchy distribution in different geographical subregions. The CDHE indicators were higher in the warmer 1994-2019 period than in the colder 1968-1993 period, but the rate of increase of the indicators was lower or there was a downward trend. Overall, CDHEs in mainland China have been in a state of remarkable continuous strengthening over the past half a century. This study provides a new quantitative analysis approach for CDHEs.

MiR-199a-5p-containing macrophage-derived extracellular vesicles inhibit SMARCA4 and alleviate atherosclerosis by reducing endothelial cell pyroptosis.

BACKGROUND: Endothelial cell disturbance underpins a role in pathogenesis of atherosclerosis. Notably, accumulating studies indicate the substantial role of microRNAs (miRs) in atherosclerosis, and miR-199a-5p dysregulation has been associated with atherosclerosis and other cardiovascular disorders. However, the effect of miR-199a-5p on the phenotypes of endothelial cells and atherosclerosis remains largely unknown. METHODS: ApoE-/- male mice were fed with high-fat diet for detection of inflammation and aorta plaque area. Extracellular vesicles (EVs) were separated from THP-1-derived macrophage (THP-1-DM) that was treated by oxidized low-density lipoprotein, followed by co-culture with human aortic endothelial cells (HAECs). Ectopic expression and downregulation of miR-199a-5p were done in THP-1-DM-derived EVs to assess pyroptosis and lactate dehydrogenase (LDH) of HAECs. Binding relationship between miR-199a-5p and SMARCA4 was evaluated by luciferase activity assay. RESULTS: EVs derived from ox-LDL-induced THP-1-DM expedited inflammation and aorta plaque area in atherosclerotic mice. Besides, miR-199a-5p expression was reduced in EVs from ox-LDL-induced THP-1-DM, and miR-199a-5p inhibition facilitated HAEC pyroptosis and LDH activity. Moreover, miR-199a-5p targeted and restricted SMARCA4, and then SMARCA4 activated the NF-κB pathway by increasing PODXL expression in HAECs. CONCLUSION: EV-packaged inhibited miR-199a-5p from macrophages expedites endothelial cell pyroptosis and further accelerates atherosclerosis through the SMARCA4/PODXL/NF-κB axis, providing promising targets and strategies for the prevention and treatment of atherosclerosis.

ONOO- -mediated oxidative modification of extracellular matrix aggravates atherosclerosis by affecting biological behaviors of vascular smooth muscle cells.

Atherosclerosis (AS) is a principal contributor to stroke and coronary heart disease in humans characterized by chronic low-grade inflammation. The extracellular matrix (ECM) plays critical roles in regulating the function of arteries. However, the effect of changes in ECM on AS development is rarely studied. In this context, we intend to study the effect of oxidizing agent peroxynitrite (ONOO- )-mediated oxidization of ECM proteins on the biological behaviors of vascular smooth muscle cells (SMCs) and the development of AS. AS mouse models were established, and mouse coronary artery smooth muscle cells (MCASMCs) were cultured in vitro to derive ECM (SMC-ECM), which was obtained by deoxycholate (DOC)-based decellularization. Further, MCASMCs were subjected to the determination of ECM oxidative damage and ECM protein structure. Finally, roles of ONOO- -mediated oxidization of ECM in SMC adhesion and migration and in AS development were explored through Transwell assay, transcriptome sequencing, and gene enrichment analysis. High concentration of ONOO- was found in the serum of AS mice, and ONOO- could stimulate the development of AS. SMC-ECM with intact structure can be obtained in vitro by DOC treatment. Functionally, ONOO- -mediated oxidization destroyed the three-dimensional structure of SMC-ECM proteins, affected SMC adhesion and migration and promoted the absorption efficiency of lipids while reducing the efflux of cholesterol. In addition, the expression of inflammation- and oxidative stress-related genes was significantly increased in ECM subjected to ONOO- -mediated oxidization, thereby contributing to AS progression. ONOO- -mediated oxidative modification of ECM aggravates AS by affecting the biological behavior of SMCs.

Attribution of local land surface temperature variations response to irrigation over the North China Plain.

Irrigation substantially alters land surface temperature (LST) in different regions of the world. Studies have recently focused on quantifying irrigation-induced LST change based on remote sensing technology due to its high spatiotemporal resolution. However, the biophysical mechanisms of irrigation on LST remains poorly understood. Here we first investigated the impact of irrigation on LST during 2003-2012 over the North China Plain (NCP), which is one of the most intensively irrigated areas around the word. We then attributed the mechanisms underlying LST change between adjacent irrigated and non-irrigated croplands based on two surface energy balance-based methods: the Decomposed Temperature Metric (DTM) method and the intrinsic biophysical mechanism (IBM) method. The results indicate that at annual scale, irrigation produce an overall cooling effect over the NCP, with the mean observed LST change of -0.098 K, calculated LST change of -0.096 K for DTM method and -0.165 K for IBM method, respectively. Furthermore, the agreement between the annual observed and calculated LST difference indicate that DTM is a more robust method than IBM in quantifying irrigation-induced LST change over the NCP. The attribution method DTM reveals that components of albedo and emissivity has an average cooling effect of -0.012 K and -0.005 K, respectively, while incoming radiation lead to a weak warming effect of +0.01 K. The enhanced turbulent fluxes of latent heat flux dominate the cooling effect (-0.174 K on average), further offsets the sensible heat flux warming effect (+0.085 K). Another attribution method IBM demonstrates that the annual cooling effect of irrigation is mostly induced by changes in aerodynamic resistance (-0.175 K), whereas the biophysical contributions of albedo (-0.0005 K) and Bowen ratio (+0.001 K) have a negligible impact on LST. This study provides a useful reference for assessing local climate impact of irrigation when implementing environmental protection projects.

The Long-Term Change of Arrhythmias after Transcatheter Closure of Perimembranous Ventricular Septal Defects.

OBJECTIVES: To observe and analyze the long-term change of different types of arrhythmias after transcatheter closure of perimembranous ventricular septal defect (pmVSD). METHODS: We retrospectively collected the data of patients who underwent pmVSD closure in our institution from March 2002 to December 2010. RESULTS: One hundred thirty-nine patients met the inclusion criteria, of which 265 (25.5%) had early arrhythmia. They were classified into two categories: conduction abnormality (191/1039; 18.4%) and origin abnormality (94/1039; 9.0%), including 20 patients with both types of arrhythmias. The median follow-up time was 84.5 months, and 103 patients (103/191; 53.9%) with early conduction block got permanent arrhythmias, while only three patients (3/94; 3.2%) with early anomalous origin arrhythmias still had an abnormal electrocardiogram. Serious arrhythmias (28/1039; 2.7%), including II° atrioventricular block (AVB), III° AVB, and complete left bundle branch block (CLBBB), can appear immediately in the early postoperative period (21 patients) or in the late outset (seven patients) after several months or even years (6 months to 8.3 years). Twenty patients (20/21; 95.2%) with serious arrhythmia in the early postoperative period improved after early treatment, but six patients relapsed or worsened during follow-up. At the endpoint, severe arrhythmia persisted in 13 patients, of which four patients got permanent pacemaker implanted, and one patient with recurrent CLBBB died from heart failure. CONCLUSIONS: The probability of delayed CAVB or bundle branch block after VSD closure is low but often occurs several years after surgery. Therefore, long-term ECG follow-up should last for several years or even decades. Serious arrhythmias that appear early after transcatheter pmVSD closure may impose a risk of recurrence although they have been cured already. Close attention should be paid to the changes of cardiac function in patients with CLBBB after VSD closure, and the severity of such arrhythmia should be taken seriously and reexamined.

Estimation of the losses in potential concentrated solar thermal power electricity production due to air pollution in China.

The concentrated solar thermal power (CSP) industry is projected to expand rapidly in China in the next 30 years. However, anthropogenic aerosol emissions reduce direct radiation (Rdir) reaching the surface, resulting in the losses of potential CSP electricity production in China. In this study, we applied various models to estimate daily Rdir, and the results showed that the gradient boosting with categorical features support (CatBoost) model was superior to other models, and coefficient of determination (R), root mean square error (RMSE) and mean absolute error (MAE) were 0.96, 1.99 MJ m-2 day-1 and 1.92 MJ m-2 day-1, respectively. We used Rdir data set at 839 stations across China derived by CatBoost model to calculate losses of the potential CSP electricity production from aerosol emissions. The results showed that the potential CSP electricity production decreased by 12.9% (136 kWh) on average at provincial level during 1961-2015. It is plausible that air quality will continue to improve from now due to the success of previous air pollution control measurements and the commitment to the United Nations of "Carbon Neutrality". It was found that returning to direct radiation levels in 1960s could yield a 15.8% increase in potential CSP electricity production, equal to 28.4-79 TWh with the expected 2050 CSP installation capacities. The corresponding economic benefits could reach 17.1-56.9 billion RMB in 2050. The findings in this study will be beneficial for siting, designing and optimizing CSP systems in China.

Impacts of preseason drought on vegetation spring phenology across the Northeast China Transect.

Vegetation phenology is undergoing profound changes in response to the recent increases in the intensity and frequency of drought events. However, the mechanisms by which drought affects the start of the growing season (SGS) are poorly understood particularly in arid and semi-arid regions. Here, we identified varying degrees of preseason drought events and analyzed the sensitivity of the SGS to preseason drought across the Northeast China Transect (NECT). Our results showed that drought caused a delayed SGS in grassland ecosystems, but an advanced SGS within forest ecosystems. These contrasting responses to preseason drought reflected different adaptive strategies between vegetation types. The SGS was shown to be highly sensitive to short timescales drought (1-3 months) in semi-arid grasslands where annual precipitation is 200-300 mm (i.e. SAGE200-300). Biomes within this region were found to be most vulnerable out of all the ecosystems to drought. Given the frequent nature of droughts in the mid-latitudes, a drought early warning system was recommended accompanied by improved modeling of how the SGS will be affected by intensified drought under future climate change.

[Spatial-temporal Distribution of Aerosol Optical Depth and Its Main Influence Types in China During 1990-2017].

In order to accurately understand the optical characteristics of aerosols in China, based on Mann-Kendall(MK) and Sen's slope trend analysis methods, the spatiotemporal variations of aerosol optical depth(AOD) derived from MERRA-2 reanalysis datasets were estimated in China for the period of 1990-2017. The results showed that ① for the interannual scale, there was a significant increasing trend in the annual mean AOD in China during 1990-2017. Besides, high aerosol loadings were observed in spring and summer, and the seasonal difference between the eastern and western regions was large. This was mainly due to the topographic and meteorological factors. ② At the spatial scale, the annual mean AOD values increased from the northwest to the southeast, with characteristically high AOD values occurring in Sichuan Pendi and the Tarim and Turpan basins and low values in the Qinghai-Xizang plateau region. Similarly, the AOD MK value and Sen's slope value showed significant decreasing trends from the southeast to the northwest, which was closely related to climate change and the human activity intensity. ③ In regard to black carbon aerosol, dust aerosol, organic carbon aerosol, sea salt aerosol, and SO4 aerosol, dust and SO4 aerosols were affected by the air humidity and human activity intensity, which have obvious regional differences in China.

Evaluating Ecosystem Services Supply and Demand Dynamics and Ecological Zoning Management in Wuhan, China.

The concept of ecosystem services (ES) supply and demand has attracted increasing attention in science and policy making because it effectively links ecosystem services to human well-being. The imbalance of ES supply and demand in urban areas has become a key issue in regional sustainable development. In this context, we calculated ES supply and demand for Wuhan City, China, using the ES supply and demand ratio (ESDR) and the comprehensive ES supply-demand ratio (CESDR) to express the relationship between ES supply and demand. Ecological zoning was proposed according to the spatial differentiation of the ES supply-demand relationship, and policy recommendations are made. The results show that from the perspective of total ES supply and demand, the water yield supply (SWY), grain yield supply (SGY), and recreation services supply (SRS) are greater than the water yield demand (DWY), grain yield demand (DGY), and recreation services demand (DRS), and that the climate regulation supply (SCR) is less than the climate regulation demand (DCR). From a spatial perspective, there are imbalances and mismatches in ES supply and demand, especially in urban central areas. The values of SWY, SGY, SCS, and SRS per unit area are less than their respective demand values, and the area of mismatch has expanded with the gradual increase of the built-up area. The spatial pattern of ES supply and demand is circular, with the form of "deficit zone-relative equilibrium zone-surplus zone", which corresponds to "urban central area-near suburbs-distant suburbs and rural areas".

Evolution of the Pattern of Spatial Expansion of Urban Land Use in the Poyang Lake Ecological Economic Zone.

To grasp the evolutionary characteristics and regularity of urban land expansion patterns in the Poyang Lake Ecological Economic Zone, this study, based on nighttime lighting data, uses the Landsat series satellite simultaneous data and cluster analysis to correct the Defense Meteorological Satellite Program⁻Operational Linescan System (DMSP-OLS) nighttime lighting data and then uses the auxiliary data-based comparison method to determine the threshold for extracting the urban built-up area. Based on this threshold, a total of eight typical landscape pattern indicators, including landscape total area, total patches number, patches density, maximum patches index, and agglomeration index, etc., are selected. Next, the landscape spatial pattern analysis method and standard deviation ellipse method are used. The results show the following: (1) In 1992⁻2013, urbanization in the Poyang Lake Ecological Economic Zone expanded rapidly. The urban built-up area increased by 8.13 times, the number of plaques increased by 1.5 times, and the shape complexity of landscape plaques gradually increased. There is a large correlation between the changes in the total boundary length, and the average boundary density, the average annual growth rate of the two is 21.33% and 17.45%. (2) The two indicators of maximum plaque index and aggregation index show a downward trend year by year. However, there are some fluctuations and irregularities in the evolution of the total landscape area, total plaque number and plaque density. (3) The long axis and the short axis of the standard deviation ellipse of the Poyang Lake Ecological Economic Zone show small variation during the inspection period and generally have an elliptical shape. The movement of the center of gravity is mainly from the southwest to the northeast, but the migration of the center of gravity is relatively small. Based on this, this paper proposes three countermeasures and suggestions as a guide to promote the optimization and development of the spatial expansion pattern of the Poyang Lake eco-economic zone.

Analysis of photosynthetically active radiation under various sky conditions in Wuhan, Central China.

Observations of photosynthetically active radiation (PAR) and global solar radiation (G) at Wuhan, Central China during 2005-2012 were first reported to investigate PAR variability at different time scales and its PAR fraction (F(p)) under different sky conditions. Both G irradiances (I(g)) and PAR irradiances (I(p)) showed similar seasonal features that peaked in values at noon during summer and reached their lower values in winter. F(p) reached higher values during either sunrise or sunset; lower values of F p appeared at local noon because of the absorption effects of water vapor and clouds on long-wave radiation. There was an inverse relationship between clearness index (K(t)) and F(p); the maximum I(p) decreased by 22.3 % (39.7 %) when sky conditions changed from overcast to cloudless in summer (winter); solar radiation was more affected by cloudiness than the seasonal variation in cloudy skies when compared with that in clear skies. The maximum daily PAR irradiation (R(p)) was 11.89 MJ m⁻² day⁻¹ with an annual average of 4.85 MJ m⁻² day⁻¹. F p was in the range of 29-61.5 % with annual daily average value being about 42 %. Meanwhile, hourly, daily, and monthly relationships between R p and G irradiation (R g) under different sky conditions were investigated. It was discovered that cloudy skies were the dominated sky condition in this region. Finally, a clear-sky PAR model was developed by analyzing the dependence of PAR irradiances on optical air mass under various sky conditions for the whole study period in Central China, which will lay foundations for ecological process study in the near future.

Mapping of Cu and Pb contaminations in soil using combined geochemistry, topography, and remote sensing: a case study in the Le'an River floodplain, China.

Heavy metal pollution in soil is becoming a widely concerning environmental problem in China. The aim of this study is to integrate multiple sources of data, namely total Cu and Pb contents, digital elevation model (DEM) data, remote sensing image and interpreted land-use data, for mapping the spatial distribution of total Cu and Pb contamination in top soil along the Le'an River and its branches. Combined with geographical analyses and watershed delineation, the source and transportation route of pollutants are identified. Regions at high risk of Cu or Pb pollution are suggested. Results reveal that topography is the major factor that controls the spatial distribution of Cu and Pb. Watershed delineation shows evidence that the streamflow resulting from rainfall is the major carrier of metal pollutants.