Cell penetration, herbicidal activity, and in-vivo-toxicity of oligo-arginine derivatives and of novel guanidinium-rich compounds derived from the biopolymer cyanophycin Grogg, Marcel and Hilvert, Donald and Ebert, Marc-Olivier and Beck, Albert K. and Seebach, Dieter and Kurth, Felix and Dittrich, Petra S. and Sparr, C. and Wittlin, Sergio and Rottmann, Matthias and Mäser, Pascal

Oligo‐arginines are thoroughly studied cell‐penetrating peptides (CPPs, Figures 1 and 2). Previous in‐vitro investigations with the octaarginine salt of the phosphonate fosmidomycin (herbicide and anti‐malaria drug) have shown a 40‐fold parasitaemia inhibition with P. falciparum, compared to fosmidomycin alone (Figure 3). We have now tested this salt, as well as the corresponding phosphinate salt of the herbicide glufosinate, for herbicidal activity with whole plants by spray application, hoping for increased activities, i.e. decreased doses. However, both salts showed low herbicidal activity, indicating poor foliar uptake (Table 1). Another pronounced difference between in‐vitro and in‐vivo activity was demonstrated with various cell‐penetrating octaarginine salts of fosmidomycin: intravenous injection to mice caused exitus of the animals within minutes, even at doses as low as 1.4 μmol/kg (Table 2). The results show that use of CPPs for drug delivery, for instance to cancer cells and tissues, must be considered with due care. The biopolymer cyanophycin is a poly‐aspartic acid containing argininylated side chains (Figure 4); its building block is the dipeptide H‐βAsp‐αArg‐OH (H‐Adp‐OH). To test and compare the biological properties with those of octaarginines we synthesized Adp8‐derivatives (Figure 5). Intravenouse injection of H‐Adp8‐NH2 into the tail vein of mice with doses as high as 45 μmol/kg causes no symptoms whatsoever (Table 3), but H‐Adp8‐NH2 is not cell penetrating (HEK293 and MCF‐7 cells, Figure 6). On the other hand, the fluorescently labeled octamers FAM‐(Adp(OMe))8‐NH2 and FAM‐(Adp(NMe2))8‐NH2 with ester and amide groups in the side chains exhibit mediocre to high cell‐wall permeability (Figure 6), and are toxic (Table 3). Possible reasons for this behavior are discussed (Figure 7) and corresponding NMR spectra are presented (Figure 8)

Global, regional, and national burden of ischemic heart disease attributable to ambient PM2.5 from 1990 to 2019: An analysis for the global burden of disease study 2019

Information on the spatio-temporal patterns of the burden of ischemic heart disease (IHD) caused by ambient ambient fine particulate matter (PM2.5) in the global level is needed to prioritize the control of ambient air pollution and prevent the burden of IHD. The Global Burden of Disease Study (GBD) 2019 provides data on IHD attributable to ambient PM2.5. The IHD burden and mortality attributable to ambient PM2.5 were analyzed by year, age, gender, socio-demographic index (SDI) level, geographical region and country. Estimated annual percentage change (EAPC) was calculated to estimate the temporal trends of age-standardized mortality rate (ASMR) and age-standardized disability-adjusted life years rate (ASDR) from 1990 to 2019. Globally, the ASMR and ASDR for ambient PM2.5-related IHD tended to level off generally, with EAPC of −0.03 (95% CI: −0.06, 0.12) and 0.3 (95% CI: 0.22, 0.37), respectively. In the past 30 years, there were obvious differences in the trend of burden change among different regions. A highest increased burden was estimated in low-middle SDI region (EAPC of ASMR: 3.73 [95% CI: 3.56, 3.9], EAPC of ASDR: 3.83 [95% CI: 3.64, 4.02]). In contrast, the burden in high SDI region (EAPC of ASMR: −4.48 [95% CI: −4.6, −4.35], EAPC of ASDR: −3.98 [95% CI: −4.12, −3.85]) has declined most significantly. Moreover, this burden was higher among men and older populations. EAPCs of the ASMR (R = −0.776, p 2.5 are stabilizing, but this burden has shifted from high SDI countries to middle and low SDI countries, especially among men and elderly populations. To reduce this burden, the air pollution management prevention need to be further strengthened, especially among males, older populations, and middle and low SDI countries.</p

Associations of greenness with diabetes mellitus and glucose-homeostasis markers: the 33 communities Chinese Health Study

Residing in greener places may be protective against diabetes mellitus (DM) but evidence is scarce and comes mainly from developed countries.To investigate associations of residential greenness with DM prevalence and glucose-homeostasis markers in Chinese adults and whether these associations were mediated by air pollution, physical activity, and body mass index.In 2009, a total of 15,477 adults from the cross-sectional 33 Communities Chinese Health Study provided blood samples and completed a questionnaire. We considered fasting and 2-h glucose and insulin concentrations, as well as the homoeostasis model assessment of insulin resistance and β-cell function, as glucose-homeostasis markers. DM was defined according to the American Diabetes Association's recommendations. Residential greenness was estimated by two satellite-derived vegetation indexes - Normalized Difference Vegetation Index (NDVI) and Soil Adjusted Vegetation Index (SAVI). Nitrogen dioxide and particulate matter ≤2.5 μm were used as air pollution proxies. Associations were assessed by two-level adjusted logistic and linear regression models.A 0.1-unit increase in NDVI and SAVI was significantly associated with lower odds of DM by factors of 0.88 (95% Confidence Interval 0.82-0.94) and 0.80 (0.72-0.90), respectively. Higher greenness was also significantly associated with lower fasting and 2-h glucose levels, 2-h insulin level, as well as lower insulin resistance and higher β-cell function. Air pollution and body mass index significantly mediated 6.9-51.1% and 8.6-78.7% these associations, respectively, while no mediation role was observed for physical activity.Higher residential greenness appears to be associated with a lower prevalence of DM. This association might be due to glucose and insulin metabolism and pancreatic β-cell function. Lower levels of air pollution and body mass index can be pathways linking greenspace to diabetes