Age- and time-of-day dependence of glymphatic function in the human brain measured via two diffusion MRI methods

Advanced age, accompanied by impaired glymphatic function, is a key risk factor for many neurodegenerative diseases. To study age-related differences in the human glymphatic system, we measured the influx and efflux activities of the glymphatic system via two non-invasive diffusion magnetic resonance imaging (MRI) methods, ultra-long echo time and low-b diffusion tensor imaging (DTIlow–b) measuring the subarachnoid space (SAS) flow along the middle cerebral artery and DTI analysis along the perivascular space (DTI-ALPS) along medullary veins in 22 healthy volunteers (aged 21–75 years). We first evaluated the circadian rhythm dependence of the glymphatic activity by repeating the MRI measurements at five time points from 8:00 to 23:00 and found no time-of-day dependence in the awake state under the current sensitivity of MRI measurements. Further test–retest analysis demonstrated high repeatability of both diffusion MRI measurements, suggesting their reliability. Additionally, the influx rate of the glymphatic system was significantly higher in participants aged >45 years than in participants aged 21–38, while the efflux rate was significantly lower in those aged >45 years. The mismatched influx and efflux activities in the glymphatic system might be due to age-related changes in arterial pulsation and aquaporin-4 polarization

Coupling effects of Fe(II) and CaCO3 application on cadmium uptake and accumulation in rice (Oryza sativa L.)

Excessive cadmium (Cd) in rice, caused by Cd pollution of farmlands, poses a serious threat to human health. In this study, a pot experiment was conducted to investigate the effects of two doses of CaCO3 (Ca1: 2 g kg-1, Ca2: 10g kg-1), two types of Fe(II) (EDTA-Fe(II) and FeSO4; 0.14 g Fe kg-1), and their combined application on the uptake and accumulation of Cd in rice plants grown in Cd-contaminated acidic soil. The results revealed that FeSO4 significantly increased rice grain biomass, whereas the other treatments had no significant effects. Further, the addition of EDTA-Fe(II) or FeSO4 significantly enhanced iron plaque formation on the root surface and increased the Fe content in the rice plants and porewater. Compared to the control, CaCO3 addition weakened the formation of iron plaque and reduced the Fe concentration in the porewater and root tissue, stems and leaves, whereas the Fe concentration in brown rice and the husks remained unaffected. Combined application of CaCO3 and Fe(II) significantly promoted the formation of iron plaque and increased the Fe concentration in brown rice. However, the Cd concentration in the iron plaque was reduced by CaCO3 addition but increased by Fe(II) treatment. Notably, all treatments reduced the Cd concentration in all rice plant tissues. The application of Ca1, Ca2, EDTA-Fe(II), FeSO4, Ca1+EDTA-Fe(II), Ca1+FeSO4, Ca2+EDTA-Fe(II) and Ca2+FeSO4 significantly reduced the Cd concentration in brown rice by 69%, 63%, 51%, 60%, 46%, 39%, 38%, and 29%, respectively. These results indicate that the application of CaCO3, EDTA-Fe(II)/FeSO4, or their combination can effectively reduce Cd accumulation and translocation in rice plants

IL-21 promotes myocardial ischaemia/reperfusion injury through the modulation of neutrophil infiltration.

BACKGROUND AND PURPOSE: The immune system plays an important role in driving the acute inflammatory response following myocardial ischaemia/reperfusion injury (MIRI). IL-21 is a pleiotropic cytokine with multiple immunomodulatory effects, but its role in MIRI is not known. EXPERIMENTAL APPROACH: Myocardial injury, neutrophil infiltration and the expression of neutrophil chemokines KC (CXCL1) and MIP-2 (CXCL2) were studied in a mouse model of MIRI. Effects of IL-21 on the expression of KC and MIP-2 in neonatal mouse cardiomyocytes (CMs) and cardiac fibroblasts (CFs) were determined by real-time PCR and ELISA. The signalling mechanisms underlying these effects were explored by western blot analysis. KEY RESULTS: IL-21 was elevated within the acute phase of murine MIRI. Neutralization of IL-21 attenuated myocardial injury, as illustrated by reduced infarct size, decreased cardiac troponin T levels and improved cardiac function, whereas exogenous IL-21 administration exerted opposite effects. IL-21 increased the infiltration of neutrophils and increased the expression of KC and MIP-2 in myocardial tissue following MIRI. Moreover, neutrophil depletion attenuated the IL-21-induced myocardial injury. Mechanistically, IL-21 increased the production of KC and MIP-2 in neonatal CMs and CFs, and enhanced neutrophil migration, as revealed by the migration assay. Furthermore, we demonstrated that this IL-21-mediated increase in chemokine expression involved the activation of Akt/NF-κB signalling in CMs and p38 MAPK/NF-κB signalling in CFs. CONCLUSIONS AND IMPLICATIONS: Our data provide novel evidence that IL-21 plays a pathogenic role in MIRI, most likely by promoting cardiac neutrophil infiltration. Therefore, targeting IL-21 may have therapeutic potential as a treatment for MIRI. LINKED ARTICLES: This article is part of a themed section on Spotlight on Small Molecules in Cardiovascular Diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.8/issuetoc

Selecting ecologically appropriate scales to assess landscape ecological risk in megacity Beijing, China

Assessing the landscape ecological risk (LER) will facilitate optimal planning of land-use patterns and mitigating regional ecological risks, especially in megacities under rapid urbanization. And selecting the appropriate spatial analysis scales is the prerequisite for accurate assessment of the LER. In this study, we demonstrate the spatio-temporal dynamics of LER by determining the appropriate spatial scales in Beijing, China from 2000 to 2020. The results indicate that a granularity of 50 m and a magnitude of 5 km are optimal for regional LER assessment. The study area had predominantly medium risks, with medium, high and higher risks accounting for approximately 70% that revealed LER was at high level. Fortunately, the high and higher risks decreased by 14.64% while low and lower risks increased by 16.62% over the past two decades, which indicated LER was on a general downward trend. The LER pattern varies from east to west, with high and higher risks clustered in the northeast and southeast of the city center, and gradually dispersing elsewhere. In contrast, low and lower risks were predominantly in the city center and western regions, expanding outward from the city center. The LER was low in built-up land and cropland in the central city, but relatively high in areas away from it. The urban fringe areas dominated by woodland and grassland exhibited a high LER. The regional LER differentiation is spatially correlated with urban expressways and significant changes in LER were predominantly observed in areas adjacent to urban expressways. Specifically, the expansion of low and lower risks occurred outward along the ring roads of Beijing, and a typical case was that the lower risks were primarily enclosed by the fifth ring road in 2000 and gradually expanded towards the areas near the sixth ring road by 2020. Moreover, the LER manifests obvious spatial agglomeration influenced by human disturbance, with apparent high-high and low-low agglomerations. It is suggested to implement landscape optimization by enhancing the landscape diversity and connectivity to effectively mitigate ecological risks. These findings will provide scientific reference for researches aimed at mitigating ecological risks and fostering high-quality sustainable development in metropolitan areas

Thermostability Improvement of L-Asparaginase from Acinetobacter soli via Consensus-Designed Cysteine Residue Substitution

To extend the application range of L-asparaginase in food pre-processing, the thermostability improvement of the enzyme is essential. Herein, two non-conserved cysteine residues with easily oxidized free sulfhydryl groups, Cys8 and Cys283, of Acinetobacter soli L-asparaginase (AsA) were screened out via consensus design. After saturation mutagenesis and combinatorial mutation, the mutant C8Y/C283Q with highly improved thermostability was obtained with a half-life of 361.6 min at 40 °C, an over 34-fold increase compared with that of the wild-type. Its melting temperature (Tm) value reaches 62.3 °C, which is 7.1 °C higher than that of the wild-type. Molecular dynamics simulation and structure analysis revealed the formation of new hydrogen bonds of Gln283 and the aromatic interaction of Tyr8 formed with adjacent residues, resulting in enhanced thermostability. The improvement in the thermostability of L-asparaginase could efficiently enhance its effect on acrylamide inhibition; the contents of acrylamide in potato chips were efficiently reduced by 86.50% after a mutant C8Y/C283Q treatment, which was significantly higher than the 59.05% reduction after the AsA wild-type treatment. In addition, the investigation of the mechanism behind the enhanced thermostability of AsA could further direct the modification of L-asparaginases for expanding their clinical and industrial applications

Increased glymphatic system activity in migraine chronification by diffusion tensor image analysis along the perivascular space

Abstract Background Preliminary evidence suggests that several headache disorders may be associated with glymphatic dysfunction. However, no studies have been conducted to examine the glymphatic activity in migraine chronification. Purposes To investigate the glymphatic activity of migraine chronification in patients with episodic migraine (EM) and chronic migraine (CM) using the diffusion tensor image analysis along the perivascular space (DTI-ALPS) method. Methods In this cross-sectional study, patients with EM, CM, and healthy controls (HCs) were included. All participants underwent a standard brain magnetic resonance imaging (MRI) examination. Bilateral DTI-ALPS indexes were calculated for all participants and compared among EM, CM, and HC groups. Correlations between the DTI-ALPS index and clinical characteristics were analyzed. Results A total of 32 patients with EM, 24 patients with CM, and 41 age- and sex-matched HCs were included in the analysis. Significant differences were found in the right DTI-ALPS index among the three groups (p = 0.011), with CM showing significantly higher values than EM (p = 0.033) and HCs (p = 0.015). The right DTI-ALPS index of CM group was significantly higher than the left DTI-ALPS index (p = 0.005). And the headache intensity was correlated to DTI-ALPS index both in the left hemisphere (r = 0.371, p = 0.011) and in the right hemisphere (r = 0.307, p = 0.038), but there were no correlations after Bonferroni correction. Conclusions Glymphatic system activity is shown to be increased instead of impaired during migraine chronification. The mechanism behind this observation suggests that increased glymphatic activity is more likely to be a concomitant phenomenon of altered vascular reactivity associated with migraine pathophysiology rather than a risk factor of migraine chronification

Phylogenetic analysis and virulence characteristics of methicillin-resistant Staphylococcus aureus ST764-SCCmec II: an emerging hypervirulent clone ST764-t1084 in China

ABSTRACTPrevious studies have shown that the increased prevalent ST764 clone in China, Japan, and other Asian areas. However, the knowledge of the genetic features and virulence characteristics of methicillin-resistant Staphylococcus aureus (MRSA) ST764 in China is still limited. In this study, we identified 52 ST764-SCCmec type II isolates collected from five cities in China between 2014 and 2021. Whole genome sequencing showed that the most common staphylococcal protein A (spa) types of ST764 in China were t002 (55.78%) and t1084 (40.38%). Virulence assays showed that ST764-t1084 isolates had high haemolytic activity and α-toxin levels. Of the critical regulatory factors affecting α-toxin production, only the SaeRS was highly expressed in ST764-t1084 isolates. Mouse abscess model indicated that the virulence of ST764-t1084 isolates was comparable to that of S. aureus USA300-LAC famous for its hypervirulence. Interestingly, ST764-t002 isolates exhibited stronger biofilm formation and cell adhesion capacities than ST764-t1084 isolates. This seems to explain why ST764-t002 subclone has become more prevalent in China in recent years. Phylogenetic analysis suggested that all ST764 isolates from China in Clade III were closely related to KUN1163 (an isolate from Japan). Notably, genomic analysis revealed that the 52 ST764 isolates did not carry arginine catabolic mobile element (ACME), which differed from ST764 isolates in Japan. Additionally, most ST764 isolates (69.23%) harboured an obvious deletion of approximately 5 kb in the SCCmec II cassette region compared to KUN1163. Our findings shed light on the potential global transmission and genotypic as well as phenotypic characteristics of ST764 lineage