The quest for improved air quality may push China to continue its CO2 reduction beyond the Paris Commitment

China is challenged with the simultaneous goals of improving air quality and mitigating climate change. The “Beautiful China” strategy, launched by the Chinese government in 2020, requires that all cities in China attain 35 μg/m³ or below for annual mean concentration of PM_2.5 (particulate matter with aerodynamic diameter less than 2.5 μm) by 2035. Meanwhile, China adopts a portfolio of low-carbon policies to meet its Nationally Determined Contribution (NDC) pledged in the Paris Agreement. Previous studies demonstrated the cobenefits to air pollution reduction from implementing low-carbon energy policies. Pathways for China to achieve dual targets of both air quality and CO₂ mitigation, however, have not been comprehensively explored. Here, we couple an integrated assessment model and an air quality model to evaluate air quality in China through 2035 under the NDC scenario and an alternative scenario (Co-Benefit Energy [CBE]) with enhanced low-carbon policies. Results indicate that some Chinese cities cannot meet the PM_2.5 target under the NDC scenario by 2035, even with the strictest end-of-pipe controls. Achieving the air quality target would require further reduction in emissions of multiple air pollutants by 6 to 32%, driving additional 22% reduction in CO₂ emissions relative to the NDC scenario. Results show that the incremental health benefit from improved air quality of CBE exceeds 8 times the additional costs of CO₂ mitigation, attributed particularly to the cost-effective reduction in household PM_2.5 exposure. The additional low-carbon energy polices required for China’s air quality targets would lay an important foundation for its deep decarbonization aligned with the 2 °C global temperature target.

China is facing serious air pollution problems, particularly for ambient PM_2.5 (particulate matter with aerodynamic diameter less than 2.5 μm) which has harmful effects on human health (1–3). To protect human health, strengthened air pollution control policies were recently implemented in China targeting 35 μg⋅m⁻³ or less for all cities by 2035 (4). The Action Plan on Prevention and Control of Air Pollution, released in 2013, has resulted in noticeable reductions in urban ambient PM_2.5 concentrations (5, 6). In 2018, however, China’s national PM_2.5 standard of 35 μg⋅m⁻³ annual average was exceeded in 217 of China’s 338 cities at the prefecture or higher level, not to mention exceedance of the World Health Organization (WHO) guideline (annual mean PM_2.5 concentration <10 μg⋅m⁻³). A big challenge for future improvement is that advanced end-of-pipe control technologies have already been widely applied in electric and industrial sectors (7, 8). For example, over 90% of coal-fired power plants had installed end-of-pipe control technologies by 2018 (8). Therefore, the potential for further reductions using end-of-pipe control measures might be limited, and implementation of low-carbon energy policies to constrain total energy consumption and promote a transition to clean energy is expected to be an inevitable option for further reducing air pollution (9).The impacts of climate change on humans and ecosystems have also received considerable attention in China over the past few decades, and strategies for mitigating these impacts have been adopted (10). In 2016, China officially signed its Nationally Determined Contribution (NDC) in the Paris Commitment, which pledges for CO₂ emissions per unit of GDP in 2030 to fall by 60 to 65% compared to 2005. A big concern arises as to whether China will continue its carbon reduction even under a pessimistic international situation after the US withdrawal from the Paris Agreement in 2019. Previous studies (11–18) have suggested that climate mitigation-oriented low-carbon energy policies can result in a reduction in air pollution.Therefore, there is a question as to whether China needs the application of low-carbon energy technologies and fuels to meet its air quality target. Such synergy is important, since many developing countries (e.g., China, India) are currently experiencing serious air pollution problems, and reducing air pollution is typically a more pressing national concern than climate mitigation (19). This could lead to continuous reductions in CO₂ emissions even under a pessimistic international situation for mitigating climate change.Here, we project future air quality attainment in China through 2035, assess the CO₂ reduction cobenefits associated with attaining the ambient PM_2.5 standards, and evaluate the health and climate impacts associated with air quality attainment-oriented energy policies. We accomplish this by coupling an integrated assessment model [GCAM, the Global Climate Assessment Model (20)], tuned with a detailed bottom-up emission inventory (21), and an air quality model [CMAQ, the Community Multiscale Air Quality model (22)] to evaluate future air quality and CO₂ emissions, and an integrated exposure−response (IER) model to evaluate the health effects due to the long-term ambient O₃ and both ambient and household PM_2.5 exposures in China. This integrated approach captures the nonlinearities among energy, emissions, concentrations, and health, thus allowing us to assess the cobenefits of air quality attainment on protecting health and mitigating CO₂ in an internally consistent framework.This study investigates future emissions of air pollutants and CO₂ in China under three future pathways with different considerations of two energy scenarios and two end-of-pipe control levels (Table 1). We first designed the NDC−current legislation (CLE) pathway to represent the CO₂ intensity reduction targets outlined by China’s NDC to meet the Paris Commitment (23), with CLE level of end-of-pipe controls. This pathway represents the current ongoing energy policies and end-of-pipe control measures to be conducted in China following CLE. For the purpose of air quality attainment, we first designed the NDC−maximum feasible reduction (MFR) pathway to represent the same ongoing energy policies as the NDC−CLE scenario, but with MFR level realized by end-of-pipe controls. Additionally, to achieve the air quality attainment in 2035, we also introduce the CBE−MFR pathway, in which low-carbon energy policies beyond the NDC requirements are implemented (i.e., the cobenefit energy scenario [CBE]) with the MFR level of end-of-pipe controls.Table 1.Design of future projection of air pollutant and CO₂ emissions

内镜发现主动脉夹层动脉瘤导致吞咽困难一例

本文报道1例内镜发现主动脉夹层动脉瘤的患者病程，包括了其症状、体征及胃镜、超声内镜和主动脉CT血管成像等检查结果。该例经心外科行介入治疗，顺利出院。当发现食管较大隆起性病变时，不能忽略主动脉瘤的存在。最好先行影像学检查，除外胸主动脉瘤后再行内镜超声检查，以降低内镜检查的风险。     

Poliovirus spreads from muscle to the central nervous system by neural pathways.

A transgenic mouse model was used to address an unsolved question in the pathogenesis of poliomyelitis: how poliovirus invades the central nervous system (CNS). LD50 values for intramuscular and intracerebral inoculation of poliovirus in transgenic mice expressing poliovirus receptors (TgPVR mice) were similar. After intramuscular inoculation with poliovirus, paralysis was observed first in the inoculated limb. In contrast, localization of initial paralysis to the inoculated limb was not observed in normal mice inoculated intramuscularly with the mouse-adapted P2/Lansing poliovirus strain. After intramuscular inoculation, infectious poliovirus was first detected in the inferior segment of the spinal cord, then in the superior spinal cord and the brain. Sciatic nerve transection blocked poliovirus spread to the spinal cord after inoculation into the hindlimb footpad of TgPVR mice. These results demonstrate that in TgPVR mice, poliovirus spreads from muscle to the CNS through nerve pathways and that expression of the poliovirus receptor plays an important role in viral spread by this route.     

Impact of device-host interaction on paravalvular aortic regurgitation with different transcatheter heart valves

Aims

We sought to evaluate the interaction of different aortic root phenotypes with self-expanding (SEV), balloon-expandable (BEV) and mechanically expanded (MEV) and the impact on significant aortic regurgitation.

PRDM6 is enriched in vascular precursors during development and inhibits endothelial cell proliferation, survival, and differentiation

The mechanisms that regulate the differentiation program of multipotential stem cells remain poorly understood. In order to define the cues that delineate endothelial commitment from precursors, we screened for candidate regulatory genes in differentiating mouse embryoid bodies. We found that the PR/SET domain protein, PRDM6, is enriched in flk1(+) hematovascular precursor cells using a microarray-based approach. As determined by 5′ RACE, full-length PRDM6 protein contains a PR domain and four Krüppel-like zinc fingers. In situ hybridization in mouse embryos demonstrates staining of the primitive streak, allantois, heart, outflow tract, paraaortic splanchnopleura (P-Sp)/aorto-gonadal-mesonephric (AGM) region and yolk sac, all sites known to be enriched in vascular precursor cells. PRDM6 is also detected in embryonic and adult-derived endothelial cell lines. PRDM6 is co-localized with histone H4 and methylates H4-K20 (but not H3) in vitro and in vivo, which is consistent with the known participation of PR domains in histone methyltransferase activity. Overexpression of PRDM6 in mouse embryonic endothelial cells induces apoptosis by activating caspase-3 and inducing G1 arrest. PRDM6 inhibits cell proliferation as determined by BrdU incorporation in endothelial cells, but not in rat aortic smooth muscle cells. Overexpression of PRDM6 also results in reduced tube formation in cultured endothelial cells grown in Matrigel. Taken together, our data indicate that PRDM6 is expressed by vascular precursors, has differential effects in endothelial cells and smooth muscle cells, and may play a role in vascular precursor differentiation and survival by modulating local chromatin-remodeling activity within hematovascular subpopulations during development.     

人促血液血管细胞生成素的高效表达和快速纯化

目的 构建人促血液血管细胞生成素（HAPO）的表达载体，获得纯化的HAPO蛋白并研究其生物学功能。方法 通过PCR方法扩增人HAPO基因，克隆于不同的原核表达载体，ITPG诱导融合蛋白表达。NTA层析柱纯化融合蛋白，再经肠激酶裂解融合蛋白，阳离子交换层析纯化，得到纯化的重组蛋白。用培养的MO7e和ECV-304细胞检测蛋白活性。结果 HAPO可在pET32C中，获得稳定高效的可溶性表达。在Ecoli BL21（DE3）中，HAPO表达量可占菌体总蛋白的10％左右。重组蛋白80％是以可溶性蛋白形式存在。NTA层析柱纯化得到的HAPO融合蛋白，再经肠激酶裂解，阳离子交换层析纯化，得到90％以上纯度的重组HAPO蛋白，并且具有良好的生物学活性。结论 得到具有90％以上纯度的重组HAPO蛋白，而且，对MO7e和ECV-304细胞具有促增殖的作用。我们获得了纯化的人重组HAPO蛋白，为进一步研究其功能及临床应用打下基础。     

Invasiveness of fibroblast-like synoviocytes is an individual patient characteristic associated with the rate of joint destruction in patients with rheumatoid arthritis

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by inflammation and destruction of synovial joints. Fibroblast-like synoviocytes (FLS) harvested from synovial tissue of patients with RA can invade normal human cartilage in severe combined immunodeficient (SCID) mice and Matrigel basement membrane matrix in vitro. This study was undertaken to investigate the association of these in vitro characteristics with disease characteristics in patients with RA. METHODS: Synovial tissue samples from 72 RA and 49 osteoarthritis (OA) patients were obtained. Samples of different joints were collected from 7 patients with RA. The FLS invasiveness in Matrigel was studied, and the intraindividual and interindividual differences were compared. From the patients with FLS who exhibited the most extreme differences in in vitro ingrowth (most and least invasive FLS), radiographs of the hands and feet were collected and scored according to the Sharp/van der Heijde method to determine the relationship between in vitro invasion data and estimated yearly joint damage progression. RESULTS: FLS from patients with RA were more invasive than FLS from patients with OA (P < 0.001). The mean intraindividual variation in FLS invasion was much less than the mean interindividual variation (mean +/- SD 1,067 +/- 926 and 3,845 +/- 2,367 for intraindividual and interindividual variation, respectively; P = 0.035), which shows that the level of FLS invasion is a patient characteristic. The mean +/- SEM Sharp score on radiographs of the hands or feet divided by the disease duration was 4.4 +/- 1.1 units per year of disease duration in patients with the least invasive FLS (n = 9), which was much lower compared with the 21.8 +/- 3.1 units per year of disease duration in patients with the most invasive FLS (n = 9) (P < 0.001). CONCLUSION: The ex vivo invasive behavior of FLS from RA patients is associated with the rate of joint destruction and is a patient characteristic, given the much smaller intraindividual than interindividual FLS variation.     

Osteopontin expression in human and murine obesity: extensive local up-regulation in adipose tissue but minimal systemic alterations

Obesity is associated with a chronic low-grade inflammation characterized by macrophage infiltration of adipose tissue (AT) that may underlie the development of insulin resistance and type 2 diabetes. Osteopontin (OPN) is a multifunctional protein involved in various inflammatory processes, cell migration, and tissue remodeling. Because these processes occur in the AT of obese patients, we studied in detail the regulation of OPN expression in human and murine obesity. The study included 20 morbidly obese patients and 20 age- and sex-matched control subjects, as well as two models (diet-induced and genetic) of murine obesity. In high-fat diet-induced and genetically obese mice, OPN expression was drastically up-regulated in AT (40 and 80-fold, respectively) but remained largely unaltered in liver (<2-fold). Moreover, OPN plasma concentrations remained unchanged in both murine models of obesity, suggesting a particular local but not systemic importance for OPN. OPN expression was strongly elevated also in the AT of obese patients compared with lean subjects in both omental and sc AT. In addition, we detected three OPN isoforms to be expressed in human AT and, strikingly, an obesity induced alteration of the OPN isoform expression pattern. Analysis of AT cellular fractions revealed that OPN is exceptionally highly expressed in AT macrophages in humans and mice. Moreover, OPN expression in AT macrophages was strongly up-regulated by obesity. In conclusion, our data point toward a specific local role of OPN in obese AT. Therefore, OPN could be a critical regulator in obesity induced AT inflammation and insulin resistance.     

Hypothalamic expression of anorexigenic and orexigenic hormone receptors in obese females Neotomodon alstoni: Effect of fasting

Obesity is a world problem that requires a better understanding of its physiological and genetic basis, as well as the mechanisms by which the hypothalamus controls feeding behavior. The volcano mouse Neotomodon alstoni develops obesity in captivity when fed with regular chow diet, providing a novel model for the study of obesity. Females develop obesity more often than males; therefore, in this study, we analysed in females, in proestrous lean and obese, the differences in hypothalamus expression of receptors for leptin, ghrelin (growth hormone secretagogue receptor GHS-R), and VPAC, and correlates for plasma levels of total ghrelin. The main comparisons are between mice fed ad libitum and mice after 24 hours of fasting. Mice above 65 g body weight were considered obese, based on behavioral and physiological parameters such as food intake, plasma free fatty acids, and glucose tolerance. Hypothalamic tissue from obese and lean mice was analysed by western blot. Our results indicate that after ad libitum food access, obese mice show no significant differences in hypothalamic leptin receptors, but a significant increase of 60% in the GHS-R, and a nearly 62% decrease in VPAC2 was noted. After a 24-hour fast, plasma ghrelin increased nearly two fold in both lean and obese mice; increases of hypothalamic leptin receptors and GHS-R were also noted, while VPAC2 did not change significantly; levels of plasma free fatty acids were 50% less after fasting in obese than in lean animals. Our results indicate that in obese N. alstoni mice, the levels of orexigenic receptors in the hypothalamus correlate with overfeeding, and the fact that lean and obese females respond in different ways to a metabolic demand such as a 24-hour fast.