Extensive epigenetic reprogramming involves in memory CD8+ T-cell differentiation. The elaborate epigenetic rewiring underlying the heterogeneous functional states of CD8+ T cells remains hidden. Here, we profile single-cell chromatin accessibility and map enhancer-promoter interactomes to characterize the differentiation trajectory of memory CD8+ T cells. We reveal that under distinct epigenetic regulations, the early activated CD8+ T cells divergently originated for short-lived effector and memory precursor effector cells. We also uncover a defined epigenetic rewiring leading to the conversion from effector memory to central memory cells during memory formation. Additionally, we illustrate chromatin regulatory mechanisms underlying long-lasting versus transient transcription regulation during memory differentiation. Finally, we confirm the essential roles of Sox4 and Nrf2 in developing memory precursor effector and effector memory cells, respectively, and validate cell state-specific enhancers in regulating Il7r using CRISPR-Cas9. Our data pave the way for understanding the mechanism underlying epigenetic memory formation in CD8+ T-cell differentiation.
CD8-Positive T-Lymphocytes/metabolism* ; Cell Differentiation ; Chromatin/immunology* ; Animals ; Mice ; Immunologic Memory ; Epigenesis, Genetic ; SOXC Transcription Factors/immunology* ; NF-E2-Related Factor 2/immunology* ; Mice, Inbred C57BL ; Gene Regulatory Networks ; Enhancer Elements, Genetic

Objective: To develop a model incorporating radiomic features and clinical factors to accurately predict acute ischemic stroke (AIS) outcomes. Materials and Methods: Data from 522 AIS patients (382 male [73.2%]; mean age ± standard deviation, 58.9 ± 11.5 years) were randomly divided into the training (n = 311) and validation cohorts (n = 211). According to the modified Rankin Scale (mRS) at 6 months after hospital discharge, prognosis was dichotomized into good (mRS ≤ 2) and poor (mRS > 2); 1310 radiomics features were extracted from diffusion-weighted imaging and apparent diffusion coefficient maps. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator logistic regression method were implemented to select the features and establish a radiomics model. Univariable and multivariable logistic regression analyses were performed to identify the clinical factors and construct a clinical model. Ultimately, a multivariable logistic regression analysis incorporating independent clinical factors and radiomics score was implemented to establish the final combined prediction model using a backward step-down selection procedure, and a clinical-radiomics nomogram was developed. The models were evaluated using calibration, receiver operating characteristic (ROC), and decision curve analyses. Results: Age, sex, stroke history, diabetes, baseline mRS, baseline National Institutes of Health Stroke Scale score, and radiomics score were independent predictors of AIS outcomes. The area under the ROC curve of the clinical-radiomics model was 0.868 (95% confidence interval, 0.825–0.910) in the training cohort and 0.890 (0.844–0.936) in the validation cohort, which was significantly larger than that of the clinical or radiomics models. The clinical radiomics nomogram was well calibrated (p > 0.05). The decision curve analysis indicated its clinical usefulness. Conclusion The clinical-radiomics model outperformed individual clinical or radiomics models and achieved satisfactory performance in predicting AIS outcomes.

The wild resources of Paris polyphylla var. yunnanensis, a secondary endangered medicinal plant, are severely scarce. Introduction and cultivation can alleviate market demand. To screen phosphatolytic bacteria in the rhizosphere soil of P. polyphylla var. yunnanensis and provide data support for the development of high-efficiency microbial fertilizer, in this study, the dilution plate coating method was used to isolate and screen the phosphorus solubilizing bacteria with the ability of mineralizing organic phosphorus from the rhizosphere soil of wild and transplanted varieties of P. polyphylla var. yunnanensis in 10 different locations in Yunnan, Sichuan and Guizhou. After separation and purification, the phosphatolytic capacity was analyzed by qualitative and quantitative analysis. Combined with physiological and biochemical experiments, the strains were identified using 16 S rDNA sequencing analysis. Forty one strains were selected from the rhizosphere soil of P. polyphylla var. yunnanensis from 10 different habitats. Among them, 21 strains were obtained from the rhizosphere soil of the wild variety P. polyphylla var. yunnanensis and 20 strains were obtained from the rhizosphere soil of the transplanted variety. And significance analysis found that 41 organophosphate solubilizing strains had significant differences in their ability to solubilize phosphorus. The amount of phosphate solubilizing was 0.08-67.61 mg·L~(-1), the pH value was between 4.27 and 6.82. The phosphatolytic amount of strain Y3-5 was 67.61 mg·L~(-1), and the phosphorus increase amount was 57.57 mg·L~(-1). All 41 strains were identified as Gram-positive Bacillus. Combining physiological characteristic and phylogenetic trees, Bacillus mobilis Y3-5 was finally selected as the candidate rhizosphere phosphatolytic bacteria of P. polyphylla var. yunnanensis. The distribution of phosphorus solubilizing bacteria in the rhizosphere soil of P. polyphylla var. yunnanensis was different, and there were significant diffe-rences in phosphorus solubility. Organophosphate-dissolving strain Y3-5 is expected to be a candidate strain of P. polyphylla var. yunnanensis microbial fertilizer.
Bacillus ; Bacteria/genetics* ; China ; Liliaceae ; Phylogeny

The study aiming at exploring the potassium-dissolving capacity of rhizosphere potassium-dissolving bacteria from diffe-rent sources and screen the strains with high potassium-dissolving ability, so as to lay a theoretical foundation for cultivation and quality improvement of Paris polyphylla var. yunnanensis sources. The rhizosphere soil of 10 wild and transplanted species from Yunnan, Sichuan and Guizhou provinces was used as the research object. Potassium-dissolving bacteria were isolated and purified, and their potassium-dissolving capacity was determined by flame spectrophotometry, and identified by physiological, biochemical and molecular biological methods. Twenty-six potassium-dissolving bacteria were purified and 13 were obtained from wild and transplanted strains respectively. It was found through the determination of potassium-dissolving capacity that the potassium-dissolving capacity of 26 strains was significantly different, and the mass concentration of K~+ in the fermentation broth were 1.04-2.75 mg·L~(-1), the mcentration of potassium were 0.01-1.82 mg·L~(-1). The strains were identified as Bacillus, Agrobacterium rhizome and Staphylococcus by physiological, biochemical and 16 S rDNA molecular methods, among them Bacillus amylolyticus(4 strains) was the dominant bacterium of Bacillus. The physiology and biochemistry of rhizosphere potassium-dissolving bacteria in P. polyphylla var. yunnanensis rhizosphere were diffe-rent, and the living environment were different, so the potassium-dissolving capacity also changed. Strain Y4-1 with the highest potassium decomposability was Bacillus amylolytic with a potassium increase of 1.82 mg·L~(-1). The potassium-dissolving ability and the distribution of potassium-dissolving bacteria were different in various habitats. The screening of potassium-dissolving bacteria provided a new strain for the preparation of microbial fertilizer. It is expected that B. amyloidococcus Y4-1 can be used as an ideal strain to cultivate mycorrhizal seedlings of P. polyphylla var. yunnanensis.
China ; Liliaceae ; Paenibacillus ; Potassium ; Rhizosphere ; Soil

Indigenous knowledge and traditional culture for sustainable use of native plants in Juenang cultural region of Rangtang county, Aba Zang and Qiang Prefecture of Sichuan province, have been characterized in this paper followed the principles and methods of ethnobotany. The results indicate that 38 species from 27 families(including 6 species of fungi) are ethnobotanically used commonly in this area. Of 38 species of the native plants, 13 species from 12 families are collected for eatables and vegetables, 12 families and 16 species of indigenous plants for medicinal and edible use, 4 species from 4 families for decoration, 4 species from 4 families used for building materials or firewood, and 1 species from 1 families used for religious folklore. Under the influence of Juenang culture and Tibetan culture, indigenous knowledge such as instinctive reverence and gratitude for nature, protection ecological environment and habitats, and moderate use of natural resources(especially wild bioresource), have been gotten passed on from generation to generation in Juenang culture region of Rangtang county, which is of great significance to the protection of local bioresources and environment, including ethnic medicinal plants, and also to provide practical guidance for biodiversity conservation and ecological restoration in those alpine ecological vulnerable areas.
Biodiversity ; China ; Conservation of Natural Resources ; Ethnobotany ; Fungi/classification* ; Humans ; Knowledge ; Phytotherapy ; Plants, Medicinal/classification*

Objective To investigate the effect of butylphthalide and sodium chloride injection on patients who received endovascular treatment for acute anterior circulation large vessel occlusive stroke.Methods A total of 173 patients were identified from February 2015 to December 2017 in the Department of Neurology of Jingling Hospital in this retrospective observational study.Propensity score-matching analysis was performed to balance differences in baseline characteristics between patients who received butylphthalide injection (butylphthalide group) and those who did not (control group).The modified Rankin Scale scores at 90 days were compared between the butylphthalide and control groups.Results A total of 144 patients who received endovascular treatment for acute anterior circulation large vessel occlusive stroke were finally analyzed,54 cases in the butylphthalide group and 90 cases in the control group.The proportion of good functional outcome at 90 days in the butylphthalide group was higher than that in the control group (63.0％ (34/54) vs 44.4％ (40/90);x2=4.633,P=0.031).Thirty-six pairs were matched successfully by the propensity score matching,36 patients in the butylphthalide group and 36 in the control group.There was no statistically significant difference in the 90-day functional outcome between the two groups (66.7％ (24/36) vs 44.4％ (16/36);x2=3.600,P=0.058).One hundred and fifteen patients were recanalized,47 cases in the butylphthalide group and 68 cases in the control group,and after the propensity score matching,30 pairs were analyzed.The proportion of good functional outcome at 90 days in the butylphthalide group was higher than that in the control group (73.3％ (22/30) vs 46.7％ (14/30);x2=4.444,P=0.035).Conclusion After propensity score-matching,butylphthalide and sodium chloride injection could improve 90-day functional outcome in patients with acute anterior circulation large vessel occlusive stroke and obtained recanalization by endovascular treatment while could not before propensity score-matching.

Glioblastoma is a common brain tumor and the overall survival rate of the patients is very low, so it is an effective way to develop the potential chemotherapy or adjuvant chemotherapy drugs in glioblastoma treatment. As a well-known antimalarial drug, artesunate(ARTs) has clear side effects, and recently it has been reported to have antitumor effects, but rarely reported in glioblastoma. Different concentrations of ARTs were used to treat the glioblastoma cells, and then the inhibitory effect of ARTs on glioblastoma proliferation was detected by MTT assay; Ki67 immunofluorescence assay was used to detect the proliferation of cells; Soft agar experiment was used to explain the clonal formation abilities ; Flow Cytometry was used to detect the cell cycle; and Western blot assay was used to determine the expression of key cell cycle protein. MTT assay results indicated that ARTs-treated glioblastoma cell A172, U251, U87 were significantly inhibited in a time-and-dose dependent manner as compared to the control group(DMSO treatment group). Soft agar experiment showed that ARTs could significantly reduce the clonal formation ability of glioblastoma. Furthermore, Flow cytometry analysis showed that ARTs could obviously increase the cell proportion in G₀/G₁ phase and reduce the cell proportion in S phase. Western blot results showed that the expressions of cell cycle-related proteins CDK2, CDK4, cyclin D1 and cyclin B1 were all obviously down-regulated. Above all, ARTs may inhibit the proliferation of glioblastoma cells by arresting cell cycle in G₀/G₁ phase through down-regulating the expression of CDK2, CDK4, cyclin D1, cyclin B1. These results may not only provide a novel method for rediscovering and reusing ARTs but also provide a new potential drug for treating glioblastoma.
Antineoplastic Agents ; pharmacology ; Apoptosis ; Artesunate ; pharmacology ; Cell Cycle Checkpoints ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Cyclin B1 ; metabolism ; Cyclin D1 ; metabolism ; Cyclin-Dependent Kinase 2 ; metabolism ; Cyclin-Dependent Kinase 4 ; metabolism ; Glioblastoma ; drug therapy ; pathology ; Humans

The major contributing factors for growth of endangered medicinal plants of Fritillariae Cirrhosae Bulbus were screened on the GIS platform by using the MaxEnt model, and spatial distribution data of the medicine quality suitability were generated by geostatistics interpolation based on reported measured data of ecology and quality suitability assessment. On this basis, a functional production cultivation regionalization with high feasibility and operability were formatted for protection, wild monitoring, and cultivation of this plant by fuzzy superposition of spatial suitability data of ecology and quality, as well as integrated with land use and cover data. Therefore, a novel assessment and regionalization method were presented for ecology, growth and quality suitability of the Chinese traditional medicinal plants. This method is expected to overcome shortage of traditional regionalization methods difficult to distinguish the contribution of ecological factors and quality factors, which provide an innovative theory and methodology for regionalization, and is helpful to practical application of wild resource protection, monitoring, and commercialization cultivation for traditional Chinese medicinal plants.

Objective To identify the diffusion alterations of deep gray matter(GM) and white matter (WM) among Alzheimer's disease (AD), mild cognitive impairment (MCI) and healthy people by atlas?based analysis (ABA), and to investigate the respective relationship with cognitive function. Methods Twenty?one AD patients (AD group), 8 MCI patients (MCI group) and 15 normal controls (control group) were performed by conventional MRI and diffusion tensor imaging (DTI). The raw data of DTI was processed by using DTI studio software to generate the fractional anisotropy (FA) images. Then ABA was used to quantify the FA value in 58 deep GM and WM structures. The differences of FA value among three groups were compared by using one way ANOVA, with a post?hoc analysis. In AD and MCI groups, the partial correlation was further investigated between mini?mental state examination (MMSE) score and FA value in the brain regions that have significant differences between AD and MCI group or between MCI and control group. Results Compared with control group, AD patients showed wide?spread FA decrease in most deep GM and WM regions (corrected P<0.05). The FA values of the hypothalamus, the fornix, the superior longitudinal fasciculus (SLF) and the cingulum in AD group were significantly lower than those in MCI group (corrected P<0.05). The FA value of the right splenium of corpus callosum (SCC) in MCI group was significantly lower than that in control group (MCI:0.550±0.018 vs. Control:0.585±0.026, P<0.05). In AD and MCI group, the FA values of the left hypothalamus, the right hypothalamus, the left cingulum, the right cingulum, and the left SLF were positively correlated with MMSE scores(r=0.502, 0.515, 0.535, 0.527, 0.512; P<0.05). No significant correlation was found between the FA value of the right SCC, the right SLF, the right fornix/stria terminalis, the right fornix and MMSE scores(P>0.05). Conclusion Based on ABA, this study found the diffusion changes not only in the WM but also the deep GM in AD patients, but only WM diffusion disruptions in MCI group. The decreased FA value in the right SCC appeared early, but had no correlation with the cognitive impairment. The FA value in the hypothalamus, the fornix, the SLF and the cingulum decreased with the disease progression, and correlated positively with the cognition decline.

BACKGROUNDPrevious studies have indicated that the cognitive deficits in patients with Alzheimer's disease (AD) may be due to topological deteriorations of the brain network. However, whether the selection of a specific frequency band could impact the topological properties is still not clear. Our hypothesis is that the topological properties of AD patients are also frequency-specific.

METHODSResting state functional magnetic resonance imaging data from 10 right-handed moderate AD patients (mean age: 64.3 years; mean mini mental state examination [MMSE]: 18.0) and 10 age and gender-matched healthy controls (mean age: 63.6 years; mean MMSE: 28.2) were enrolled in this study. The global efficiency, the clustering coefficient (CC), the characteristic path length (CpL), and "small-world" property were calculated in a wide range of thresholds and averaged within each group, at three different frequency bands (0.01-0.06 Hz, 0.06-0.11 Hz, and 0.11-0.25 Hz).

RESULTSAt lower-frequency bands (0.01-0.06 Hz, 0.06-0.11 Hz), the global efficiency, the CC and the "small-world" properties of AD patients decreased compared to controls. While at higher-frequency bands (0.11-0.25 Hz), the CpL was much longer, and the "small-world" property was disrupted in AD, particularly at a higher threshold. The topological properties changed with different frequency bands, suggesting the existence of disrupted global and local functional organization associated with AD.

CONCLUSIONSThis study demonstrates that the topological alterations of large-scale functional brain networks in AD patients are frequency dependent, thus providing fundamental support for optimal frequency selection in future related research.

Aged ; Aged, 80 and over ; Alzheimer Disease ; diagnosis ; Brain ; pathology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged