Currently, Alzheimer's disease (AD) cannot be treated effectively. Mesenchymal stem cells (MSCs)-derived extracellular vesicles (EVs) (MSC-EVs) exhibit therapeutic effects on many diseases. This ...study investigated the mechanism of bone marrow MSC-EVs (BM-MSC-EVs) in a rat model of AD. The cognitive function, amyloid-β (Aβ) plaques, Aβ deposition areas and levels of Aβ1-42, Aβ decomposition-related factors (NEP and IDE), and inflammatory cytokines in BM-MSC-EVs-treated AD rats were measured. The effect of BM-MSC-EVs was studied in AD neuron model. microRNA (miR)-29c-3p and BACE1 expression, as well as levels of Wnt/β-catenin pathway-related factors in AD and EVs-treated AD models were detected. miR-29c-3p relationship with BACE1 was predicted and confirmed. miR-29c-3p and BACE1 were interfered to verify the mechanism of EVs in AD. The Wnt/β-catenin pathway inhibitor DKK1 was further added to EVs-treated AD neurons. BM-MSC-EVs showed therapeutic effects on AD rats and neurons. BM-MSC-EVs carried miR-29c-3p into AD neurons. miR-29c-3p targeted BACE1. Silencing miR-29c-3p in BM-MSCs reduced BM-MSC-EV therapeutic effect on AD, which was reversed after BACE1 knockdown. miR-29c-3p targeted BACE1 and activated the Wnt/β-catenin pathway, and the Wnt/β-catenin pathway inhibition impaired EV therapeutic effects on AD. We highlighted that BM-MSC-EVs delivered miR-29c-3p to neurons to inhibit BACE1 expression and activate the Wnt/β-catenin pathway, thereby playing a therapeutic role in AD. This study may provide a novel perspective for elucidating the mechanism of MSCs in the treatment of AD.
We report on the highest energy photons from the Crab Nebula observed by the Tibet air shower array with the underground water-Cherenkov-type muon detector array. Based on the criterion of a muon ...number measured in an air shower, we successfully suppress 99.92% of the cosmic-ray background events with energies E>100 TeV. As a result, we observed 24 photonlike events with E>100 TeV against 5.5 background events, which corresponds to a 5.6σ statistical significance. This is the first detection of photons with E>100 TeV from an astrophysical source.
Because CT plays an important role in diagnosis, isolation, treatment, and effective evaluation of coronavirus disease (COVID-19), infection prevention and control management of CT examination rooms ...is important.
We describe modifications to the CT examination process, strict disinfection of examination rooms, arrangement of waiting areas, and efforts to increase radiographers' awareness of personal protection made at our institution during the COVID-19 outbreak. In addition, we discuss the potential of using artificial intelligence in imaging patients with contagious diseases.
Ginsenoside Rg1 is regarded as one of main bioactive compounds responsible for pharmaceutical actions of ginseng with little toxicity and has been shown to have possibly neuroprotective effects. ...However, the mechanism of its neuroprotection for acute ischemic stroke is still elusive. The purpose of present study is thus to assess the neuroprotective effects of the ginsenoside Rg1 against neurological injury in a mice model of cerebral ischemia/reperfusion (I/R), and then to explore the mechanisms for these neuroprotective effects.
Mices were pretreated with ginsenoside Rg1 20,40 mg kg−1 d−1, ig, for 7d, respectively, then subjected to cerebral ischenmia (middle cerebral artery occlusion) for 2 h and reperfusion for 22 h. The infarct volume and the neurological deficit were determined by TTC staining and Longa′s scoring, respectively. The protein expression of brain-derived neurotrophic factor (BDNF) was analyzed by Immunohistochemistry and Western blot, respectively. Interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) expression in serum was measured by ELISA kit. High-performance liquid chromatography (HPLC) was used to explore the contents of Glu and Asp.
Compared with the ischemia/reperfusion group, ginsenoside Rg1 40 mg/kg group has significantly reduced infarct volume, neurological deficit scores (P < .05), Interleukin-1β (IL-1β), tumor necrosis factor alpha (TNF-α) and interleukin-6 (IL-6) contents in serum (p < .01, respectively), the contents of Glu and Asp (P < .01). Immunohistochemistry and Western blot indicated that ginsenoside Rg1 40 mg/kg group significantly increased brain-derived neurotrophic factor (BDNF) protein expression in the CA1 regions of the hippocampus (p < .01).
Ginsenoside Rg1 40 mg/kg has protective effects on cerebral injury induced by ischeamia/reperfusion, which might be related to the increased in the expression of BDNF in the hippocampal CA1 region, the down-regulation of the expression of IL-1β、IL-6 and TNF-α in serum, the decreases in the contents of Glu and Asp in the brain tissue.
This study evaluated the anaesthetic and sedative effects of eugenol applied on yellow catfish (Pelteobagrus fulvidraco). In the anaesthesia induction and recovery experiment, fish were treated with ...five concentrations of eugenol (0, 15, 20, 25 and 30 mg/L), respectively, and in the transportation experiment, fish treated with 10 mg/L eugenol were evaluated after 12 h simulated transportation. Induction and recovery time were recorded. The induction time shortened with the increasing eugenol concentration, whereas the recovery time prolonged with the increasing eugenol concentration. The effective concentration of eugenol for short‐term anaesthesia induction was between 25 and 30 mg/L. The post‐transportation survival rate of yellow catfish was 100%. The content of ammonia nitrogen in the eugenol group was lower (p < 0.05). Compared with the control group, yellow catfish in the anaesthetized transportation group showed a significant decrease in blood cortisol levels (p < 0.05), whereas the levels of glucose and lysozyme significantly increased (p < 0.05). Both hsp70 and hsp90 mRNA expression in the liver of anaesthetized yellow catfish were found to significantly upregulate after transportation (p < 0.05). In summary, eugenol was an effective anaesthetic for yellow catfish. For short‐term anaesthesia, the recommended concentration is 25–30 mg/L and for long‐time transportation, the appropriate concentration is 10 mg/L in order to reduce stress response of fish.
Objectives
To develop a predictive model and scoring system to enhance the diagnostic efficiency for coronavirus disease 2019 (COVID-19).
Methods
From January 19 to February 6, 2020, 88 confirmed ...COVID-19 patients presenting with pneumonia and 80 non-COVID-19 patients suffering from pneumonia of other origins were retrospectively enrolled. Clinical data and laboratory results were collected. CT features and scores were evaluated at the segmental level according to the lesions’ position, attenuation, and form. Scores were calculated based on the size of the pneumonia lesion, which graded at the range of 1 to 4. Air bronchogram, tree-in-bud sign, crazy-paving pattern, subpleural curvilinear line, bronchiectasis, air space, pleural effusion, and mediastinal and/or hilar lymphadenopathy were also evaluated.
Results
Multivariate logistic regression analysis showed that history of exposure (
β
= 3.095, odds ratio (OR) = 22.088), leukocyte count (
β
= − 1.495, OR = 0.224), number of segments with peripheral lesions (
β
= 1.604, OR = 1.604), and crazy-paving pattern (
β
= 2.836, OR = 2.836) were used for establishing the predictive model to identify COVID-19-positive patients (
p
< 0.05). In this model, values of area under curve (AUC) in the training and testing groups were 0.910 and 0.914, respectively (
p
< 0.001). A predicted score for COVID-19 (PSC-19) was calculated based on the predictive model by the following formula: PSC-19 = 2 × history of exposure (0–1 point) − 1 × leukocyte count (0–2 points) + 1 × peripheral lesions (0–1 point) + 2 × crazy-paving pattern (0–1 point), with an optimal cutoff point of 1 (sensitivity, 88.5%; specificity, 91.7%).
Conclusions
Our predictive model and PSC-19 can be applied for identification of COVID-19-positive cases, assisting physicians and radiologists until receiving the results of reverse transcription–polymerase chain reaction (RT-PCR) tests.
Key Points
• Prediction of RT-PCR positivity is crucial for fast diagnosis of patients suspected of having coronavirus disease 2019 (COVID-19).
• Typical CT manifestations are advantageous for diagnosing COVID-19 and differentiation of COVID-19 from other types of pneumonia.
• A predictive model and scoring system combining both clinical and CT features were herein developed to enable high diagnostic efficiency for COVID-19.
e16520 Background: Venous tumor thrombus (VTT) is observed in 4−10% of newly diagnosed RCC patients, and a successful radical nephrectomy and thrombectomy provides considerable palliation to a ...proportion of nonmetastatic RCC patients with VTT. However, the reported postsurgical survival varies significantly with the 5‐year overall survival (OS) rate ranging from 37.0 to 71.0%. Hence, accurate risk factors are critically needed for these patients. Here we evaluate the prognostic significance of VTT grading for these patients. Methods: The final evaluable dataset enrolled 706 consecutively nonmetastatic ccRCC patients who underwent radical nephrectomy and thrombectomy, including 304 in the Training cohort from the Eastern China Renal Cancer Collaborative Group, 320 in the China‐Validation cohort and 82 in the Poland‐Validation cohort. All pathological specimens were centrally reviewed by three genitourinary pathologists blinded to clinical information. Univariable and multivariable Cox regression analyses were performed to identify independent predictors associated with survival outcomes. Results: To comprehensively evaluate the potential of VTT in risk assessment, multiple characteristics of VTT were incorporated, including VTT height, consistency and the pathological nuclear grading of VTT (VTT grading), which has not been studied yet. Although higher pathological grading of primary tumor (PT) and VTT were both significantly correlated with dismal prognosis, only VTT grading remained as an independent predictive factor for OS and DFS after multivariable Cox regression. Furthermore, VTT grading showed superiority in risk assessment compared with PT grading and other variables by c‐index analysis (OS: 0.663 vs. 0.501–0.610, 0.667 vs. 0.544–0.651, and 0.719 vs. 0.511–0.700 for Training, China‐Validation, and Poland‐Validation cohorts, respectively; DFS: 0.664 vs. 0.501–0.606, and 0.672 vs. 0.530–0.640 for Training, and China‐Validation cohorts, respectively), which was confirmed by the receiver operating characteristic (ROC) analysis (OS: area under the curve AUC 0.764 vs. 0.650–0.664, 0.684 vs. 0.650–0.667, and 0.814 vs. 0.641–0.711 for Training, China‐Validation, and Poland‐Validation cohorts, respectively; DFS: AUC 0.753 vs. 0.648–0.651, and 0.704 vs. 0.601–0.665 for Training, and China‐Validation cohorts, respectively). Conclusions: VTT grading displayed superior accuracy and discriminatory ability in predicting survival risk for nonmetastatic ccRCC patients with VTT. Assessing VTT grading in routine pathology reports may provide further information for stratification of patient risk.
e16524 Background: Renal cell carcinoma (RCC) patients suffering from local recurrence (LR) herald variable risk of second progression even after curative surgery for LR. Further risk stratification ...of these patients will facilitate selection of candidates for adjuvant immunotherapy. Here we evaluate the prognostic significance of tumor grade variation (GV) between the primary tumor (PT) and LR tumor in nonmetastatic RCC in the largest study to date. Methods: We reviewed Research of Multi-institution in East-China on Malignant and Benign Epithelial Renal Tumors (REMEMBER) database to identify ccRCC or pRCC patients who underwent surgery for LR. All pathology slides were centrally reviewed by three independent senior genitourinary pathologists and patients were assigned to groups based on GV as upgrading (WHO/ISUP Ⅰ/Ⅱ for PT grade and Ⅲ/Ⅳ for LR grade), downgrading (WHO/ISUP Ⅲ/Ⅳ for PT grade and Ⅰ/Ⅱ for LR grade), stable low-grade (WHO/ISUP Ⅰ/Ⅱ for both PT and LR grade) and stable high-grade groups (WHO/ISUP Ⅲ/Ⅳ for both PT and LR grade). To evaluate the predictive value of GV, four tumor grade measures (PT grade, LR grade, highest grade for the PT and LR, GV) were separately incorporated for model development. The primary end point was overall survival (OS), defined as the time from LR surgery to death from any cause or last follow-up. A multivariable cox regression analysis was performed to explore associations between timing and survival. Results: 345 patients were identified 114 stable low-grade (33.1%), 56 downgrading (16.2%), 97 upgrading (28.1%), and 78 stable high-grade (22.6%). Median OS were highest among patients with stable low-grade (114 stable low-grade vs. 86 Downgrading vs. 59 Upgrading vs. 33 Stable high-grade months). Univariate analysis indicates that PT, LR and GV were significant correlated with poor OS (all P values < 0.05). After separately constructing the PT grade model (#1) via LASSO cox regressions for predicting OS, LR grade model (#2), highest grade model (#3) and GV model (#4) were built by simply replacing the variable of PT grade, it turned out that GV model (#4) achieved the better discriminatory ability (AUC of model (#4) vs. model (#1), 0.812 vs. 0.743; model (#4) vs. model (#2), 0.812 vs. 0.788; model (#4) vs. model (#3), 0.812 vs. 0.762, all p values < 0.05). Conclusions: This is the first study showing that GV is independently associated with clinical outcomes in patients with LR. Routine reporting of LR upgrading or downgrading in relation to the PT and assessment of GV can facilitate more informed treatment decisions by tailoring strategies to an individual patient's risk of progression.
To realize the effective extraction of high-temperature thermal energy in enhanced geothermal system (EGS), it is necessary to explore how to efficiently construct fracture network in hot dry rock ...(HDR). Considering the cryogenic induced thermal stress, we investigate the cracking mechanism when using supercritical CO2 (SCCO2) and hydraulic fracturing to stimulate HDR. Firstly, the established three-dimensional THMD coupling model is verified by conducting high temperature granite fracturing experiments. Then, characteristics of the heat and mass transfer and fracture propagation when using SCCO2 and H2O in HDR fracturing are explored. Finally, the cracking mechanism of hydraulic and SCCO2 fracturing in HDR under thermal stress is revealed. The results indicate that the cryogenic induced thermal stress can reduce the cracking pressure and tend to form branch fractures under the cooperation of injection pressure. Adopting SCCO2 in HDR fracturing more micro fractures can be generated in near-well zone. Hydraulic fracturing has better cooling efficiency and preferably capability of extending fractures. For HDR fracturing, the scope of fracture network tends to increase first and then decrease with the raise of injection mass flux. The lower viscosity and higher specific heat capacity of fracturing fluid can promote the formation of fracture network.
•True-triaxial fracturing tests on granites are conducted under different temperature.•Three-dimensional THMD coupling model is established to simulate hot rock fracturing.•Damage evolution of hydraulic and SCCO2 fracturing in HDR stimulation is investigated.•Effect of injection mass flux on fracture morphology in HDR fracturing is researched.•Lower viscosity and higher heat capacity of fracturing fluid can promote the formation of EGS.
A diabetic ulcer (DU) is a dreaded and resistant complication of diabetes mellitus with high morbidity. Fu-Huang ointment (FH ointment) is a proven recipe for treating chronic refractory wounds; ...however, its molecular mechanisms of action are unclear. In this study, we identified 154 bioactive ingredients and their 1127 target genes in FH ointment through the public database. The intersection of these target genes with 151 disease-related targets in DUs resulted in 64 overlapping genes. Overlapping genes were identified in the PPI network and enrichment analyses. The PPI network identified 12 core target genes, whereas Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that upregulation of the PI3K/Akt signalling pathway was involved in the role of FH ointment in treating diabetic wounds. Molecular docking showed that 22 active compounds in FH ointment could enter the active pocket of PIK3CA. Molecular dynamics was used to prove the binding stability of the active ingredients and protein targets. We found that PIK3CA/Isobutyryl shikonin and PIK3CA/Isovaleryl shikonin combinations had strong binding energies. An in vivo experiment was conducted on PIK3CA, which was the most significant gene.This study comprehensively elucidated the active compounds, potential targets, and molecular mechanism of FH ointment application in treating DUs, and believed that PIK3CA is a promising target for accelerated healing.
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•Exploring the regulatory mechanism of Fu-Huang ointment in the treatment of diabetic ulcers based on bioinformatics methods.•Accelerated healing of diabetic ulcer by Fu-Huang ointment is associated with activation of PIK3CA.•Isobutyryl shikonin and Isovaleryl shikonin, the active ingredients of Fu-Huang ointment, had strong combination with PIK3CA.
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