Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke.

Ischemic stroke is the leading cause of adult disability. The rewiring of surviving neurons is the fundamental process for functional recovery. Accumulating evidence implicates astrocytes in synapses and neural circuits formation, but few studies have further studied how to enhance the effects of astrocytes on synapse and circuits after stroke and its impacts on post-stroke functional recovery. In this study, we made use of chemogenetics to specifically activate astrocytic Gi signaling in the peri-infarcted sensorimotor cortex at different time epochs in a mouse model of photothrombotic stroke. We found that early activation of astrocytic hM4Di after stroke by CNO modulates astrocyte activity and upregulates synaptogenic molecules including thrombospondin-1 (TSP1) as revealed by bulk RNA-sequencing, but no significant improvement was observed in dendritic spine density and behavioral performance in grid walking test. Interestingly, when the manipulation was initiated at the subacute phase of stroke, the recovery of spine density and motor function could be effectively promoted, accompanied by increased TSP1 expression. Our data highlight the important role of astrocytes in synapse remodeling during the repair phase of stroke and suggest astrocytic Gi signaling activation as a potential strategy for synapse regeneration, circuit rewiring, and functional recovery.

Novel binary regulated silicon-carbon materials as high-performance anodes for lithium-ion batteries.

The massive volume dilation, unsteady solid electrolyte interphase, and weak conductivity about Si have failed to bring it to practical applications, although its potential capacity is up to 4200 mAh g-1. For solving these problems, novel binary regulated silicon-carbon materials (Si/BPC) were done by a sol-gel procedure combined with single carbonization. Analytical techniques were systematically utilized to examine the effects of element doping at several gradients on morphology, structure and electrochemical properties of composites, thus the optimal content was identified. Si/BPC preserves a discharge specific capacity of 1021.6 mAh g-1with a coulomb efficiency of 99.27% after 180 cycles at 1000 mA g-1, within the upgrade than single-doped and undoped. In rate test, it has a specific capacity of 1003.2 mAh g-1at a high current density of 5000 mA g-1, quickly back towards 2838.6 mAh g-1at 200 mA g-1. The inclusion of B and P elements is linked to the electrochemical characteristics. In the co-doped carbon layers, the synergistic impact of doping B and P accelerates the diffusion kinetics of lithium ions, boosts diffusion rate of Li+, offers low electrochemical impedance (45.75 Ω). This brings more defects to provide transport carriers and induces a substantial amount of electrochemically active sites, which fosters the storage of Li+, thus making silicon material electrochemically more active and potential.

The relationship between self-assessment living standard and mental health among the older in rural China: the mediating role of sleep quality.

BACKGROUND AND OBJECTIVE: Mental health imbalance are the main cause of anxiety, depression and happiness reduction in the older. Self-assessment living standard and sleep quality are both influencing factors of mental health. Meantime, self-assessment living standard has an impact on sleep quality. But there's no research on the relationship between the three, we conducted this study to explore the relationship between self-assessment living standard and mental health and the mediating role of sleep quality among the older in rural areas of China. METHODS: Using typical field sampling method, M County, Anhui Province was selected as the investigation site, and a total of 1223 respondents were selected. With the help of questionnaires enclosing respondents' sociodemographics information, 12 Items General Health Questionnaire (GHQ-12) and Pittsburgh Sleep Quality Scale (PSQI), face-to-face interviews were used to collect data. Bootstrap test was used for data analysis. RESULTS: The results showed that the age of the respondents ranged from 60 to 99 years, with an average age of (66.53 ± 6.77) years, the proportion of the older with a tendency to mental health problems was 24.7%. Most of the older people's self-assessment living standard was normal (average score was 2.89 ± 0.726), accounting for 59.3% of the total. The average sleep quality score was (6.97 ± 4.066), and 2.5% of the respondents reported serious sleep problems. older with low self- assessment living standards were more likely to report a higher propensity for psychological problems (ß = 0.420, P < 0.001) and poorer sleep quality (ß = 0.608, P < 0.001) than older with high self- assessment living standards. Mental health of the older may be related to sleep quality (ß = 0.117, P < 0.001). In addition, the effect of self- assessment living standard on mental health was significantly mediated by sleep quality (ß = 0.071, P < 0.001). CONCLUSION: Mental health is associated with self-assessment living standard, with this association mediated by sleep quality. A reasonable mechanism needs to be established to improve self-assessment living standard and sleep quality.

Astrocytic p75NTR expression provoked by ischemic stroke exacerbates the blood-brain barrier disruption.

The disruption of the blood-brain barrier (BBB) plays a critical role in the pathology of ischemic stroke. p75 neurotrophin receptor (p75NTR ) contributes to the disruption of the blood-retinal barrier in retinal ischemia. However, whether p75NTR influences the BBB permeability after acute cerebral ischemia remains unknown. The present study investigated the role and underlying mechanism of p75NTR on BBB integrity in an ischemic stroke mouse model, middle cerebral artery occlusion (MCAO). After 24 h of MCAO, astrocytes and endothelial cells in the infarct-affected brain area up-regulated p75NTR . Genetic p75NTR knockdown (p75NTR+/- ) or pharmacological inhibition of p75NTR using LM11A-31, a selective inhibitor of p75NTR , both attenuated brain damage and BBB leakage in MCAO mice. Astrocyte-specific conditional knockdown of p75NTR mediated with an adeno-associated virus significantly ameliorated BBB disruption and brain tissue damage, as well as the neurological functions after stroke. Further molecular biological examinations indicated that astrocytic p75NTR activated NF-κB and HIF-1α signals, which upregulated the expression of MMP-9 and vascular endothelial growth factor (VEGF), subsequently leading to tight junction degradation after ischemia. As a result, increased leukocyte infiltration and microglia activation exacerbated brain injury after stroke. Overall, our results provide novel insight into the role of astrocytic p75NTR in BBB disruption after acute cerebral ischemia. The p75NTR may therefore be a potential therapeutic target for the treatment of ischemic stroke.

Correlation between functional disability and quality of life among rural elderly in Anhui province, China: a cross-sectional study.

OBJECTIVE: We aimed to explore the correlation between functional disability and quality of life (QoL). And exploring the interaction of functional disability, basic demographic characteristics and health-related information on QoL among the rural elderly in Anhui Province. METHODS: This study used multi-stage stratified cluster sampling in rural Anhui Province from January to July 2018 to conduct a cross-sectional survey of older adults who met the inclusion criteria. The Five-Dimensional European Quality Of Health Scale (EQ-5D) and the WHO Disability Assessment Schedule (WHODAS2.0) scale were used to evaluate the QoL and functional disability, and the basic demographic characteristics of the survey subjects were also collected. Using binary logistic and Classification and regression tree model (CART) models to analyze the data, explore the relationship between functional disability and QoL in the elderly. RESULTS: A total of 3491 older adults were included in the survey, and 3336 completed the entire survey, with an effective response rate of 95.56%. After adjusting for covariables, those who had limited in dimension of mobility (AOR=2.243, 95%CI: 1.743-2.885), getting along (AOR=1.615, 95%CI: 1.173-2.226), life activities (AOR=2.494, 95%CI:1.928-3.226), and social participation (AOR=2.218, 95%CI: 1.656-2.971) had a lower QoL. However, the dimension of cognition (AOR=0.477, 95%CI: 0.372-0.613) is a protective factor for QoL. Additionally, we also observe that 96.3% of those who were unemployed and limited in both mobility and life activities dimensions had a lower QoL, but among those who were robust in both mobility and social participation dimensions and not suffer from chronic diseases, 56.3% had a higher QoL. CONCLUSIONS: Our findings indicate that special attention should be paid to the elderly who are unemployed, have limited in cognition, getting along, social participation, mobility, life activities and cognition robust to improve their QoL. This research is of great significance for formulating targeted strategies and measures to improve the QoL for rural elderly.

The CD200/CD200R signaling pathway contributes to spontaneous functional recovery by enhancing synaptic plasticity after stroke.

BACKGROUND: Spontaneous functional recovery occurs during the acute phase after stroke onset, but this intrinsic recovery remains limited. Therefore, exploring the mechanism underlying spontaneous recovery and identifying potential strategies to promote functional rehabilitation after stroke are very important. The CD200/CD200R signaling pathway plays an important role in neurological recovery by modulating synaptic plasticity during multiple brain disorders. However, the effect and mechanism of action of the CD200/CD200R pathway in spontaneous functional recovery after stroke are unclear. METHODS: In this study, we used a transient middle cerebral artery occlusion (MCAO) model in rats to investigate the function of CD200/CD200R signaling in spontaneous functional recovery after stroke. We performed a battery of behavioral tests (Longa test, adhesive removal test, limb-use asymmetry test, and the modified grip-traction test) to evaluate sensorimotor function after intracerebroventricular (i.c.v.) injection with CD200 fusion protein (CD200Fc) or CD200R blocking antibody (CD200R Ab) post-stroke. Density and morphology of dendritic spines were analyzed by Golgi staining. Microglia activation was evaluated by immunofluorescence staining. Western blot was used to detect the levels of protein and the levels of mRNA were measured by qPCR. RESULTS: Our study demonstrated that sensorimotor function, synaptic proteins, and structures were gradually recovered and CD200R was transiently upregulated in ipsilateral cortex after stroke. Synapse-related proteins and dendritic spines were preserved, accompanied by sensorimotor functional recovery, after stereotaxic CD200Fc injection post-stroke. In addition, CD200Fc restrained microglia activation and pro-inflammatory factor release (such as Il-1, Tnf-α, and Il-6) after MCAO. On the contrary, CD200R Ab aggravated sensory function recovery in adhesive removal test and further promoted microglia activation and pro-inflammatory factor release (such as Il-1) after MCAO. The immune-modulatory effect of CD200/CD200R signaling might be exerted partly by its inhibition of the MAPK pathway. CONCLUSIONS: This study provides evidence that the CD200/CD200R signaling pathway contributes to spontaneous functional recovery by enhancing synaptic plasticity via inhibition of microglia activation and inflammatory factor release.

Distribution, sources, and ecological risk assessment of SVOCs in surface sediments from Guan River Estuary, China.

The contamination of semi-volatile organic compounds (SVOCs) in the surface sediments of the Guan River Estuary, China was fully investigated. Total concentrations of 56 species of SVOCs ranged from 132 to 274 ng/g with an average of 186 ng/g (dry weight). Polycyclic aromatic hydrocarbon (PAH) concentrations were positively correlated with clay content and negatively correlated with sediment grain size. Source identification indicated that PAHs originated mainly from pyrolytic sources. However, intense ship traffic in the estuary may provide sources of petrogenic PAHs. Organochlorine pesticides (OCPs) mainly originated from direct input of dichlorodiphenyltrichloroethanes (DDTs) during some industrial processes. The SVOC concentrations were also compared with International Sediments Quality Guidelines and Sediments Quality Criteria, and the results indicated that negative biological impacts may originate from high concentrations of FLO, p,p'-DDE, and total DDTs.

Gender specific cut-off points of age for disability among rural elderly in Anhui Province, China.

Objective: The purpose of this study was to determine the optimal cut-off values of age for disability in order to predict the risk of disability for older adults in rural areas. Methods: WHO Disability Assessment Schedule 2.0 was used to assess disability. The cut-off values of age for disability were obtained by ROC curve analysis. Results: The cut-off points of age for cognition restriction, mobility restriction, self-care restriction, getting along with people restriction, life activities restriction, and social participation restriction for men were 70.5, 68.5, 72.5, 70.5, 71.5, and 68.5 years old, respectively. The cut-off points of age for cognition disability, mobility restriction, self-care disability, getting along with people disability, life activities disability, and social participation disability for women were 72.5, 71.5, 70.5, 70.5, 71.5, and 71.5 years old, respectively. Over the cut-off values of age was an independent risk factor for disability (P < 0.05). Conclusion: Presenting first disability symptoms were different between men and women. Preventive efforts to prevent future disability should be different for men and women.

Dietary therapy in abdominal aortic aneurysm - Insights from clinical and experimental studies.

Abdominal aortic aneurysm (AAA) is a prevalent vascular disease with high mortality rates upon rupture. Despite its prevalence in elderly populations, there remain limited treatment options; invasive surgical repair, while risky, is the only therapeutic intervention with proven clinical benefits. Dietary factors have long been suggested to be closely associated with AAA risks, and dietary therapies recently emerged as promising avenues to achieve non-invasive management of a wide spectrum of diseases. However, the role of dietary therapies in AAA remains elusive. In this article, we will summarize the recent clinical and pre-clinical efforts in understanding the therapeutic and mechanistic implications of various dietary patterns and therapeutic approaches in AAA.

Identification of Candidate Genes for Lint Percentage and Fiber Quality Through QTL Mapping and Transcriptome Analysis in an Allotetraploid Interspecific Cotton CSSLs Population.

Upland cotton (Gossypium hirsutum) has long been an important fiber crop, but the narrow genetic diversity of modern G. hirsutum limits the potential for simultaneous improvement of yield and fiber quality. It is an effective approach to broaden the genetic base of G. hirsutum through introgression of novel alleles from G. barbadense with excellent fiber quality. In the present study, an interspecific chromosome segment substitution lines (CSSLs) population was established using G. barbadense cultivar Pima S-7 as the donor parent and G. hirsutum cultivar CCRI35 as the recipient parent. A total of 105 quantitative trait loci (QTL), including 85 QTL for fiber quality and 20 QTL for lint percentage (LP), were identified based on phenotypic data collected from four environments. Among these QTL, 25 stable QTL were detected in two or more environments, including four for LP, eleven for fiber length (FL), three for fiber strength (FS), six for fiber micronaire (FM), and one for fiber elongation (FE). Eleven QTL clusters were observed on nine chromosomes, of which seven QTL clusters harbored stable QTL. Moreover, eleven major QTL for fiber quality were verified through analysis of introgressed segments of the eight superior lines with the best comprehensive phenotypes. A total of 586 putative candidate genes were identified for 25 stable QTL associated with lint percentage and fiber quality through transcriptome analysis. Furthermore, three candidate genes for FL, GH_A08G1681 (GhSCPL40), GH_A12G2328 (GhPBL19), and GH_D02G0370 (GhHSP22.7), and one candidate gene for FM, GH_D05G1346 (GhAPG), were identified through RNA-Seq and qRT-PCR analysis. These results lay the foundation for understanding the molecular regulatory mechanism of fiber development and provide valuable information for marker-assisted selection (MAS) in cotton breeding.

8-Acetyl-4-methyl-2-oxo-2H-chromen-7-yl acetate.

In the title compound, C(14)H(12)O(5), the benzopyran-2-one ring system is approximately planar [maximum deviation = 0.018 (1) Å]; the mean plane is oriented at dihedral angles of 52.26 (11) and 72.92 (7)°, respectively, to the acetyl and acet-oxy groups. In the crystal, π-π stacking is observed between parallel benzene rings of adjacent mol-ecules, the centroid-centroid distance being 3.6774 (17) Å. Inter-molecular weak C-H⋯O hydrogen bonding, and C=O⋯C=O [O⋯C = 3.058 (3) Å] and C=O⋯π [O⋯centroid = 3.328 (2) Å] inter-actions occur in the crystal structure.

Nogo receptor impairs the clearance of fibril amyloid-ß by microglia and accelerates Alzheimer's-like disease progression.

Alzheimer's disease (AD) is characterized by the progressive accumulation of ß-amyloid (Aß)-containing amyloid plaques, and microglia play a critical role in mediating Aß clearance. Mounting evidence has confirmed that the ability of microglia in clearing Aß decreased with aging and AD progress, but the underlying mechanisms are unclear. Previously, we have demonstrated that Nogo receptor (NgR), a receptor for three axon growth inhibitors associated with myelin, can decrease adhesion and migration of microglia to fibrils Aß with aging. However, whether NgR expressed on microglia affect microglia phagocytosis of fibrils Aß with aging remains unclear. Here, we found that aged but not young microglia showed increased NgR expression and decreased Aß phagocytosis in APP/PS1 transgenic mice. NgR knockdown APP/PS1 mice showed simultaneous reduced amyloid burden and improved spatial learning and memory, which were associated with increased Aß clearance. Importantly, Nogo-P4, an agonist of NgR, enhanced the protein level of p-Smad2/3, leading to a significant transcriptional inhibition of CD36 gene expression, which in turn decreased the microglial phagocytosis of Aß. Moreover, ROCK accounted for Nogo-P4-induced activation of Smad2/3 signaling. Finally, the decreasing effect of NgR on microglial Aß uptake was confirmed in a mouse model of intra-hippocampal fAß injection. Our findings suggest that NgR may play an important role in the regulation of Aß homeostasis, and has potential as a therapeutic target for AD.

Long-term inhibition of dipeptidyl-peptidase 4 reduces islet infiltration and downregulates IL-1ß and IL-12 in NOD mice.

Dipeptidyl-peptidase 4 (DPP-4) inhibitor (sitagliptin) is a novel anti-hyperglycemia drug in the treatment of type 2 diabetes. However, its potential in type 1 diabetes is still unclear. Recent studies show that increased infection, especially respiratory tract infection, is significantly associated with DPP-4 inhibitors. In this study, we aimed to explore the effects of long-term inhibition of DPP- 4 on innate immunity in type 1 diabetes. Forty mice were randomly divided into 4 groups (n = 10 in each group): control group, lipopolysaccharide (LPS) group, sitagliptin group and sitagliptin + LPS group. The concentrations of IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12, TNF-α and IFN-γ were measured with Mesco Scale Discovery multiplexed-assay kit. Immunohistochemistry staining of pancreases was performed and insulitis scores for each islet were determined. The results showed that DPP-4 inhibition has no effect on incident rate of diabetes and metabolic parameters in NOD mice. Long-term inhibition of DPP-4 reduced CD4+T cells to infiltrate into islets and ameliorated insulitis in NOD mice. DPP-4 inhibition downregulated serum interleukin IL-1ß and IL-12 in NOD mice. However, it had no significant effect on LPS-induced IL-1ß, IL-6, IL-10, IL-12, tumor necrosis factor (TNF)-α and interferon (IFN)-γ in NOD mice. In conclusion, Long-term inhibition of DPP-4 exists anti-inflammatory effect in type 1 diabetes probably by reducing CD4+T cells to infiltrate into islets and downregulating L-1ß and IL-12 in serum.

The accumulation of microplastics in fish from an important fish farm and mariculture area, Haizhou Bay, China.

Marine fisheries and aquaculture can match growing demand for marine protein from an increasing population. However, the microplastics (MPs) in marine environments may pose a threat to human health through food chains by seafood consumption. The MPs have been found lodged in the digestive tracts and other tissues of various sea animals, nevertheless, little is known in regard to the accumulation of MPs in fish from major fish farms and mariculture areas, especially in non-digestive tissues of fishes. This study investigated the accumulation of MPs in six major wild fish species (including Thryssa kammalensis, Amblychaeturichthys hexanema, Odontamblyopus rubicundus, Cynoglossus semilaevis, Chaeturichthys stigmatias and Collichthys lucidus), both in digestive and non-digestive tissues, from an important fish farm and mariculture area, Haizhou Bay, China. All fishes had items that were identified as MPs. The highest abundance of MPs was 22.21±1.70items/individual or 11.19±1.28items/g in T. kammalensis, which is filter-feeding and usually inhabits in estuary. The lowest abundance of MPs was observed in C. semilaevis (13.54±2.09items/individual) and C. stigmatias (1.61±0.56items/g). The abundance of MPs exponentially increased with the decrease of MPs size. The MPs were dominated by fiber in shape, black or grey in colour and cellophane in composition. As to different tissues, the total number of MPs on skin (800) or in gills (746) was higher than that in gut (514). In terms of skin, the abundances of MPs in three species of scaleless fish with mucus (A. hexanema, C. stigmatias and O. rubicundus) were generally higher than other three fishes with scales (C. lucidus, C. semilaevis and T. kammalensis), implying the potential high risk of scaleless fish consumption for human health in Haizhou Bay. More in-depth studies need to focus on the scaleless fish through mucus adsorbing enormous MPs.

[Determination of organochlorine and organophosphorus pesticides in soil by gas chromatography-tandem mass spectrometry with accelerated solvent extraction].

A method based on gas chromatography-tandem mass spectrometry (GC-MS/MS) coupled with accelerated solvent extraction (ASE) was developed for the determination of eight organochlorine pesticides (OCPs) and five organophosphorus pesticides (OPPs) in soils. The soil samples were grinded after freeze-drying. Particles with diameters lower than 250 µm were chosen by ion-sieving. After this, 10.0 g soil mixed with 2.0 g diaomite was extracted with hexane-acetone (1:1, v/v). The extracts were dehydrated with anhydrous sodium sulfate and concentrated with a termovap sample concentrator. The concentrated solutions were further cleaned up with Si SPE columns and eluted with hexane-acetone (1:1, v/v). The purified solutions were then isolated by HP-5MS column (30 m×0.25 mm×0.25 µm) and detected using the multiple reaction monitoring mode at the electron impact source. It is observed that this method has good linearities in the range of 1.00-100 µg/L for the 13 compounds, and the correlation coefficients (R) were greater than 0.995. The spiked recoveries of the 13 compounds were in the range of 66.8%-88.4%, and the relative standard deviations were less than 10%. With 10.0 g of sampling weight, the method detection limits ranged from 0.02 to 0.04 µg/kg for the eight OCPs and from 0.06 to 0.12 µg/kg for the five OPPs. This method is suitable for the determination of trace OCPs and OPPs in soils.

Distribution, sources and ecological risk assessment of PAHs in surface sediments from Guan River Estuary, China.

The contamination of surface sediments in Guan River Estuary, China, by polycyclic aromatic hydrocarbons (PAHs) has been fully investigated. Total concentrations of 21 PAHs ranged from 90 to 218 ng/g with an average of 132.7 ng/g, which is relatively low in comparison with other estuaries around the world. PAH concentrations appeared to be positively correlated with clay content and negatively correlated with sediment grain size. Source identification implied that the PAHs originated mainly from pyrolytic sources. However, source patterns may be continuously changed to a petrogenic origin due to the heavy ship traffic and continuous discharge of oily sewage in this area. The PAH levels were also compared with international Sediments Quality Guidelines and Sediments Quality Criteria, and the results indicated low negative effects for most individual PAHs. However, toxic effects related to FLO would occur occasionally in most locations in the estuary.