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1.
IEEE Trans Vis Comput Graph ; 26(1): 23-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31425097

RESUMO

We propose InSituNet, a deep learning based surrogate model to support parameter space exploration for ensemble simulations that are visualized in situ. In situ visualization, generating visualizations at simulation time, is becoming prevalent in handling large-scale simulations because of the I/O and storage constraints. However, in situ visualization approaches limit the flexibility of post-hoc exploration because the raw simulation data are no longer available. Although multiple image-based approaches have been proposed to mitigate this limitation, those approaches lack the ability to explore the simulation parameters. Our approach allows flexible exploration of parameter space for large-scale ensemble simulations by taking advantage of the recent advances in deep learning. Specifically, we design InSituNet as a convolutional regression model to learn the mapping from the simulation and visualization parameters to the visualization results. With the trained model, users can generate new images for different simulation parameters under various visualization settings, which enables in-depth analysis of the underlying ensemble simulations. We demonstrate the effectiveness of InSituNet in combustion, cosmology, and ocean simulations through quantitative and qualitative evaluations.

2.
IEEE Trans Vis Comput Graph ; 26(1): 34-44, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31425114

RESUMO

Complex computational models are often designed to simulate real-world physical phenomena in many scientific disciplines. However, these simulation models tend to be computationally very expensive and involve a large number of simulation input parameters, which need to be analyzed and properly calibrated before the models can be applied for real scientific studies. We propose a visual analysis system to facilitate interactive exploratory analysis of high-dimensional input parameter space for a complex yeast cell polarization simulation. The proposed system can assist the computational biologists, who designed the simulation model, to visually calibrate the input parameters by modifying the parameter values and immediately visualizing the predicted simulation outcome without having the need to run the original expensive simulation for every instance. Our proposed visual analysis system is driven by a trained neural network-based surrogate model as the backend analysis framework. In this work, we demonstrate the advantage of using neural networks as surrogate models for visual analysis by incorporating some of the recent advances in the field of uncertainty quantification, interpretability and explainability of neural network-based models. We utilize the trained network to perform interactive parameter sensitivity analysis of the original simulation as well as recommend optimal parameter configurations using the activation maximization framework of neural networks. We also facilitate detail analysis of the trained network to extract useful insights about the simulation model, learned by the network, during the training process. We performed two case studies, and discovered multiple new parameter configurations, which can trigger high cell polarization results in the original simulation model. We evaluated our results by comparing with the original simulation model outcomes as well as the findings from previous parameter analysis performed by our experts.

3.
Cell Signal ; 65: 109423, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31639491

RESUMO

Osteoarthritis (OA) is the most common disease of joint tissues; unfortunately, there are currently no curative therapies available for OA. Chondrocytes, the only cell type residing in cartilage, secrete many types of collagen (the mainly one is type II collagen) and aggrecan, which are the main components of the cartilage matrix. Chondrocyte apoptosis can lead to OA degenerative progression. We previously indicated that recombinant human midkine (rhMK), as a chondrocyte growth factor has a significant reparative effect on cartilage injury animal models. However, the molecular mechanism of this restorative function remains under investigation. Herein, we focused on the molecular mechanism underlying the role of MK in promoting the proliferation of chondrocytes cultured in vitro. Chondrocytes from rats and OA patients were successfully isolated by the digestion of articular cartilage using type II collagenase, and their proliferation was evaluated by a CCK8 assay and flow cytometry. rhMK stimulated the proliferation of chondrocytes from both OA patients and rats. Furthermore, qRT-PCR, shRNA-mediated knockdown, Western blot and immunoprecipitation (IP) assays were performed to identify the receptor and key elements responsible for the role of MK in promoting chondrocyte proliferation. Low-density lipoprotein receptor-related protein 1 (LRP1) was identified as the dominant MK receptor in chondrocytes that, as a translocator, mediates the endocytosis of MK. After being transferred into chondrocytes, MK was shown to form a complex with nucleolin that interacts with the active form of K-Ras. Upon the activation of ERK1/2, cyclin D1 expression was upregulated, promoting the chondrocyte cell cycle. Our data reveal for the first time the role of the MK-LRP1-nucleolin signaling pathway in facilitating MK-induced chondrocyte proliferation, thus providing a strong theoretical foundation for the further use of MK in OA clinical therapy.

4.
Clin J Pain ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31714323

RESUMO

BACKGROUND: Dexmedetomidine potentially confers advantage to reduce the incidence of postoperative delirium in surgical patients. Anti-inflammation is another remarkable effect of this sedative drug. In this study, we aimed to investigate whether the effect of dexmedetomidine on the postoperative cognitive function is via inhibiting peripheral inflammation. METHODS: A prospective, randomized controlled study was conducted with patients 65 years of age or older who received total knee hip arthroplasty from January 2019 to May 2019. The patients were randomly assigned to receive a spinal anesthesia supplemented with propofol or dexmedetomidine for sedation. Incidence of postoperative delirium was the primary endpoint and was determined with the Confusion Assessment Method, and incidence of postoperative cognitive dysfunction was assessed with the Mini-Mental State Examination. Blood samples were collected postoperatively to test the plasma concentrations of IL-6, TNF-α and S100ß. RESULTS: 366 patients were randomly assigned to two groups. Patients received dexmedetomidine sedation had lower incidences of postoperative delirium and better postoperative cognitive function than the patients sedated with propofol. There was no difference in postoperative plasma concentrations of TNF-α and IL-6 between the two groups. The concentration of S100ß at 48 hours after surgery was higher in patients sedated with propofol than patients received dexmedetomidine sedation. CONCLUSION: Intraoperative sedation with dexmedetomidine conferred better postoperative neurocognitive function for elderly patients received total knee hip arthroplasty. This effect was unrelated to the modulation of dexmedetomidine on peripheral inflammation.

5.
Br J Haematol ; 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-31725190

RESUMO

We explored the prognostic factors for children with very high-risk (VHR) Philadelphia chromosome (Ph) negative B-cell acute lymphoblastic leukaemia (B-ALL) and compared the therapeutic effects of intensive chemotherapy and unmanipulated haploidentical haematopoietic stem cell transplantation (haplo-HSCT) as post-remission treatment in these patients undergoing first complete remission (CR1). A total of 104 paediatric patients with VHR B-ALL in CR1 were retrospectively enrolled in this study, including 42 receiving unmanipulated haplo-HSCT (Group A) and 62 receiving ongoing chemotherapy (Group B). Estimated 3-year overall survival (OS), disease-free survival (DFS) and cumulative incidence of relapse (CIR) at 36·2 months median follow-up were 69·5 ± 4·7%, 63·5 ± 4·8% and 32·4 ± 4·7%, respectively. Maintenance of persistent positive or conversion from negative to positive of measurable residual disease (MRD) and chemotherapy were independent risk factors associated with inferior long-term survival and higher CIR. OS, DFS, and CIR differed significantly between the groups in patients with persistent positive or negative-to-positive MRD. Haplo-HSCT may be an option for children with VHR Ph-negative B-ALL in CR1, especially for patients with persistent positive or negative-to-positive MRD, and could achieve better survival than intensive chemotherapy as post-remission treatment.

6.
J Cell Biochem ; 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31692102

RESUMO

Amplified in breast cancer 1 (AIB1) is overexpression in various cancers and promotes tumor cell proliferation, survival, and invasiveness. However, the role of AIB1 in the regulation of gastric cancer (GC) cell epithelial-mesenchymal transition (EMT) is still largely unclear. In the present study, immunohistochemistry showed that AIB1 was upregulated in our cohort of patients with GC and correlated with poor survival. Knockdown of AIB1 reduced the invasive ability of GC cells, downregulated the expression of epithelial cell marker E-cadherin, and upregulated mesenchymal cell marker vimentin. AIB1 overexpression elicited the opposite effect. PI-103, the inhibitor of the PI3K/AKT signaling, partially reversed AIB1 overexpression mediated a decrease in E-cadherin and an increase in vimentin. The present data demonstrated that AIB1 augmented the EMT via activation of PI3K/AKT signaling. In conclusion, our results suggested a novel role of AIB1 in GC invasion and EMT and raised the possibility of using this molecule as an indicator for GC treatment.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31704470

RESUMO

Basiliximab has been used successfully as a second-line treatment for steroid-refractory (SR) acute graft-versus-host disease (aGVHD) in adult patients after haploidentical hematopoietic stem cell transplantation (haplo-HSCT) but has not been studied separately in the pediatric setting. We retrospectively reviewed 100 pediatric patients after haplo-HSCT receiving basiliximab for grades II (57%), III (27%), and IV (16%) SR-aGVHD between January 2015 and December 2017. The median number of basiliximab doses was 4 (range, 2-9). The day 28 overall response rate (ORR) was 85%, with complete response (CR) in 74% of patients, partial response (PR) in 11% of patients, and no response in 15% of patients. The day 28 ORR was 94.6% in skin SR-aGVHD, 81.6% in gut SR-aGVHD, and 66.7% in liver SR-aGVHD. Infectious complications included bacterial infection (11%), presumed or documented fungal infections (7%), CMV viremia (53%), EBV viremia (11%), HHV-6 viremia (7%), and HSV viremia (1%). The 3-year overall survival (OS), disease-free survival (DFS), nonrelapse mortality (NRM), and relapse rates between responders and nonresponders were 81.3% vs. 46.7% (P<0.001), 79.0% vs. 46.7% (P=0.001), 6.1% vs. 33.3% (P<0.001), and 14.9% vs. 20.0% (P=0.46), respectively. We conclude that basiliximab is an effective second-line agent for pediatric patients with SR-aGVHD after haplo-HSCT, particularly for skin SR-aGVHD.

8.
J Endod ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31753516

RESUMO

INTRODUCTION: We have previously shown that intracanal metformin ameliorates apical periodontitis, partially by modulation of osteoblast apoptosis. The action of metformin on other cell types pertinent to the development of apical periodontitis needs to be examined. In the present study, we aimed to analyze whether its effects on the expression of inducible nitric oxide synthase (iNOS) and monocyte recruitment contribute to the therapeutic effect on apical periodontitis. METHODS: Lipopolysaccharide (LPS)-induced expression of iNOS in a human monocytic cell line, Mono-Mac-6, was assessed by Western blot. The amount of nitrite in culture medium was assessed to quantify nitric oxide (NO) production. C-C motif chemokine ligand-2 (CCL-2) synthesis was measured by enzyme-linked immunosorbent assay. Experimental apical periodontitis in rats was treated with root canal debridement with or without intracanal metformin medication. Lesion progression was assessed by conventional radiography and micro-computed tomographic imaging. Cellular expression of iNOS and the number of monocytes/macrophages were assessed by immunohistochemistry. RESULTS: Metformin suppressed LPS-induced iNOS and NO production by monocytes. More importantly, metformin inhibited LPS-enhanced CCL-2 synthesis through modulation of the iNOS/NO pathway. Intracanal metformin reduced bone resorption associated with apical periodontitis and suppressed iNOS expression and monocyte recruitment. CONCLUSIONS: Our results confirmed the therapeutic efficacy of intracanal metformin for apical periodontitis. Suppression of monocyte recruitment through modulation of iNOS expression and NO production is an important mechanism underlying the beneficial effect of metformin.

9.
Bioresour Technol ; : 122387, 2019 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-31735696

RESUMO

This work developed a novel two-stage bioprocess for electricity generation from bakery waste (BW). In the first stage, commercial glucoamylase was utilized to hydrolyze the BW to produce soluble BW hydrolysate. It was found that 100 g BW could be converted to 32 g hydrolysis solid and 760 mL BW hydrolysate. The highest glucose production of 21.9 g/L could be achieved within 5 h. In the second stage, the soluble BW hydrolysate was utilized as feedstock for electricity generation in microbial fuel cell (MFC). The maximum voltage of 0.386 V was obtained. The power density reached a peak value of 29.96 mW/m2 when the external resistance was 1090 Ω. It could be potentially utilized to transform high-starch containing raw materials into biofuels production which could reduce the cost of biofuels production effectively for industrial application.

10.
Brain Behav ; : e01453, 2019 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-31709780

RESUMO

INTRODUCTION: Fine particulate matter (PM2.5) is closely associated with many neurological disorders including neurodegenerative disease, stroke, and brain tumors. However, the toxic effects of PM2.5 on neurodevelopment remain unclear. In this study, we aimed to determine the neurotoxic effects of early postnatal exposure to PM2.5 in immature and mature rats. METHODS: We exposed neonatal rats to PM2.5 (2 or 10 mg/kg body weight) through intranasal instillation from postnatal day (PND) 3-15, once a day. Emotional and cognitive development were evaluated using the elevated plus maze, forced swimming, and Morris water maze tests. Hippocampal tissue was collected and subjected to transmission electron microscopy observation and western blot analysis. RESULTS: Rats had lower body weight after exposure to high dose of PM2.5. The behavioral test results indicated that high-dose PM2.5 exposure led to increased anxiety-like symptoms in immature and mature rats, apparent depressive-like behaviors in mature rats, and impaired spatial learning and memory abilities in immature rats, and low-dose PM2.5 exposure increased anxiety-like behaviors in immature rats. Further, high-dose PM2.5 exposure contributed to fewer synapses, thinner postsynaptic density, and shorter active zone in immature and mature rats, and also decreased expressions of synaptophysin (SYP), growth associated protein-43 (GAP43), and postsynaptic density-95 (PSD95) in immature rats, SYP and PSD95 in mature rats. Moreover, low-dose PM2.5 exposure diminished the expression of PSD95 in immature rats. In addition, high-dose PM2.5 exposure reduced brain-derived neurotrophic factor (BDNF) expression and cAMP response element binding protein (CREB) phosphorylation in both immature and mature rats, and low-dose PM2.5 exposure lessened BDNF expression and CREB phosphorylation in immature rats. CONCLUSIONS: Our findings indicate that PM2.5 impairs emotional and cognitive development by disrupting structural synaptic plasticity, possibly via the CREB/BDNF signaling pathway.

11.
J Immunother Cancer ; 7(1): 313, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31753019

RESUMO

BACKGROUND: The standard treatment for epithelial ovarian carcinoma (EOC) is surgery followed by platinum/paclitaxel-based chemotherapy, but the overall survival rate is poor. The purpose of this study was to investigate the therapeutic potential of chemotherapy combined with inhibition of B and T lymphocyte attenuator (BTLA) for clinical use to treat EOC. METHODS: Initially, we evaluated the potential application of chemotherapy combined with anti-BTLA antibody in an animal model. We then analyzed the distribution and regulation of BTLA expression on immunocytes in vitro. Finally, we examined the correlation between BTLA expression levels in cancerous tissues and prognosis in 254 EOC cases. RESULTS: The combination of chemotherapy and anti-BTLA antibody for inhibiting BTLA significantly reduced peritoneal tumor volume and extended survival in tumor-bearing mice. In addition, BTLA could be identified mostly on B lymphocytes, especially on CD19hi B cells, rather than on T lymphocytes and natural killer cells. Under regulation of interleukins 6 and 10, more BTLA+CD19hi B lymphocytes could be induced through AKT and STAT3 signaling pathways. Detectable BTLA expression in ovarian cancerous tissues was associated with worse disease-free and overall survivals of EOC patients. CONCLUSIONS: BTLA detected in cancerous tissues can predict poor outcome of EOC patients. Inhibition of BTLA combined with chemotherapy can elevate immune activation and generate potent anti-tumor effects. Thus, the combination of chemotherapy and anti-BTLA antibody may hold potential clinical application for the treatment of EOC patients. TRIAL REGISTRATION: The Trial Registration Number was NCT00854399.

12.
BMJ Open ; 9(11): e030293, 2019 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-31767583

RESUMO

INTRODUCTION: The best approach for choledocholithiasis remains a matter of debate. Choledocholithiasis is usually treated with endoscopic sphincterotomy (EST), laparoscopic common bile duct exploration (LCBDE) or laparoscopic transcystic common bile duct exploration (LTCBDE). Data pertaining to the clinical outcomes of these approaches in the management of patients with cholecysto-choledocholithiasis in China are limited. An analysis of the economic burden associated with these treatments is lacking. The Chinese REgistry Study on the Treatment of Cholecysto-Choledocholithiasis (CREST Choles) was designed to address these issues in a real-world setting. METHODS AND ANALYSIS: CREST Choles was an ambispective, multicenter, observational, open-cohort study. A total of 2700 patients undergoing one of the three treatments (EST+laparoscopic cholecystectomy (LC), LCBDE+LC and LTCBDE+LC) during the period from 1 January 2013 to 1 December 2018 at participating centres were enrolled in the study. Patients with gallstones and confirmed common bile duct stones were included. Data pertaining to demographics, disease history, procedural details, imaging features and follow-up were collected. Follow-up was conducted at least 6 months after enrolment in the study and annual follow-up will be conducted until December 2020. The primary outcome is the rate of adverse outcomes within 3 years postoperatively. Economic analysis (eg, incremental cost-effectiveness ratio) would be performed to compare expense across treatments. ETHICS AND DISSEMINATION: Ethical approval was obtained at all participating centres. The registry presented is the first attempt to comprehensively evaluate the cost of treatment for cholecysto-choledocholithiasis in China. Findings are expected to be available in 2020 and will facilitate clinical decision making in such cases. TRIAL REGISTRATION NUMBER: NCT02554097.

13.
Nat Prod Res ; : 1-8, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31674834

RESUMO

Investigation into the chemical diversity of Artemisia argyi led to the discovery of two new (1, 4) and four known (2-3, 5-6) sesquiterpenoids. The new structures were determined via extensive spectroscopic data, including IR, UV, MS, and NMR, and the absolute configurations of these compounds were elucidated by calculated ECD method. All isolates were tested for their inhibitory activity against NO production in RAW 264.7 macrophages, and the isolated sesquiterpenoids exhibited NO production inhibitory activity with IC50 values ranging from 1.91 to 36.52 µM.

15.
Biochemistry ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31702899

RESUMO

Amyloid-ß (Aß) oligomers are well-known toxic molecular species associated with Alzheimer's disease. Recent discoveries of the ability of amyloid fibril surfaces to convert soluble proteins into toxic oligomers suggested that these surfaces could serve as therapeutic targets for intervention. We have shown previously that a short helical peptide could be a key structural motif that can specifically recognize the K16-E22 region of the Aß40 fibril surface with an affinity at the level of several micromolar. Here, we demonstrate that in-tether chiral center-induced helical stabilized peptides could also recognize the fibril surfaces, effectively inhibiting the surface-mediated oligomerization of Aß40. Moreover, through extensive computational sampling, we observed two distinct ways in which the peptide inhibitors recognize the fibril surface. Apart from a binding mode that, in accord with the original design, involves hydrophobic side chains at the binding interface, we observed much more frequently another binding mode in which the hydrophobic staple interacts directly with the fibril surface. The affinity of the peptides for the fibril surface could be adjusted by tuning the hydrophobicity of the staple. The best candidate investigated here exhibits a submicromolar affinity (∼0.75 µM). Collectively, this work opens an avenue for the rational design of candidate drugs with stapled peptides for amyloid-related disease.

16.
Neuroscience ; 421: 48-58, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31682826

RESUMO

Increasing studies have revealed that metabolic disorders, especially diabetes, are high risk factors for the development of Alzheimer's disease (AD) and other neurodegenerative diseases. It has been reported that patients with diabetes are prone to suffer from cognitive dysfunction (CD). Although abnormal glucose metabolism and deposition of amyloid ß (Aß) are proven to have a closely relationship with diabetes-induced CD, its exact mechanism is still undetermined. In this study, a total of 14 mice were intraperitoneally injected with streptozotocin for 5 consecutive days to mimic diabetic models, and then hierarchical cluster analysis was adopted to classify the diabetic mice into CD and Non-CD phenotypes by the results of Morris water maze test (MWMT). Furthermore, we detected Hippo signaling including mammalian sterile 20-like protein kinases1 (MST1), large tumor suppressors 1 (LATS1), Yes-associated protein (YAP) and phosphorylation of YAP (p-YAP) in brain and peripheral tissues. As compared with control mice, the levels of MST1, LATS1 and p-YAP/YAP ratio were increased in medial prefrontal cortex (mPFC), striatum and hippocampus of CD mice, while these proteins were decreased in gut tissue of CD mice. Additionally, there were significant positive correlations between escape latency and p-YAP/YAP ratio in mPFC, anterior cingulate cortex (ACC) and hippocampus, as well as the level of LATS1 in liver, kidney and gut tissues. In conclusion, alterations in Hippo signaling may contribute to CD induced by diabetes. Therefore, therapeutic interventions improving Hippo signaling might be beneficial to the treatment of diabetes-induced CD and other neurodegenerative diseases.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31705243

RESUMO

OBJECTIVES: To determine the rate of prophylactic embolization of extrahepatic vessels in patients undergoing yttrium-90 selective internal radiotherapy (90Y SIRT) for hepatocellular carcinoma (HCC) with the use of catheter-directed computed tomography hepatic angiography (CD-CTHA). MATERIALS AND METHODS: This retrospective study included 186 HCC patients who received 90Y SIRT from May 2010 to June 2015 in a single institution. All procedures were performed in a hybrid angiography-CT suite equipped with digital subtraction angiography (DSA) and CD-CTHA capabilities. CD-CTHA was performed during pre-treatment hepatic angiography. 90Y SIRT was administered approximately 2 weeks later. Selective prophylactic embolization of extrahepatic vessels was performed if extrahepatic enhancement was seen on CD-CTHA or if an extrahepatic vessel opacified on DSA/CD-CTHA despite the final microcatheter position for 90Y microsphere delivery being beyond the origin of this vessel. RESULTS: Thirty-five patients (18.8%) required selective embolization of extrahepatic vessels. Technical success of 90Y SIRT was 99.5%. Two patients (1.1%) developed radiation-induced gastrointestinal ulceration, and one (0.54%) developed radiation-induced pneumonitis. Extrahepatic uptake of 90Y microspheres was seen in the gallbladder of one patient without significant complications. CONCLUSION: The use of CD-CTHA in 90Y SIRT of HCC was associated with a low rate of prophylactic embolization of extrahepatic vessels while maintaining a high technical success rate of treatment and low rate of complications. LEVEL OF EVIDENCE: Level 4, case series.

18.
Environ Pollut ; : 113517, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31761585

RESUMO

In this paper, the acute toxicity of monobutyl phthalate (MBP), the main hydrolysis product of dibutyl phthalate, on adult zebrafish liver antioxidant system was studied. Compared the toxicity effect of MBP and DBP by histopathology and apoptosis experiments, we speculated that the toxic effects of DBP on animals may be caused by its metabolite MBP. The results indicated that the antioxidant Nrf2-Keap1 pathway was insufficient to resist MBP-induced hepatotoxicity and led to an imbalance of membrane ion homeostasis and liver damage. Decreased cell viability, significant tissue lesions and early hepatocyte apoptosis were observed in the zebrafish liver in MBP exposure at high concentration (10 mg/L). The activities of antioxidant enzymes and ATPases in zebrafish liver were inhibited with increased malondialdehyde (MDA) content and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities. Integrated biomarker response (IBR) calculation results indicated that MBP mainly inhibited catalase (CAT) activity. Simultaneously, the expression of antioxidant-related genes (SOD, CAT, GPx, Nrf2, HO-1) was down-regulated, while apoptosis-related genes (p53, bax, cas3) were significantly up-regulated.

19.
Aging (Albany NY) ; 112019 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-31760385

RESUMO

It is well recognized that type 2 diabetes mellitus (T2DM) is an age-related metabolic disease, emerging gradually as a major global health burden that has gained public attention. Meanwhile, increasing attention is paid to the crucial role of gut microbiota in the pathogenesis and therapeutic mechanisms of metabolic disorders, especially T2DM. In this study, we used C57 BL/KS db/db male mice as a T2DM murine model. We found that the ß-diversity and relative abundances of gut bacteria were obviously altered in db/db mice, associated with a significant increase in Verrucomicrobia at six levels (phylum, class, order, etc.) and family S24-7 and a significant decrease in Bacteroidaceae at family, genus, and species levels, as well as Prevotellaceae at family and genus levels. Furthermore, fecal bacteria from db/db and m/m mice transplanted into pseudo-germ-free mice showed a significant change in the metabolic parameters, including the body weight, fasting blood glucose, fluid and food intake, and alterations in the composition of the gut microbiota. Taken together, these findings suggest that abnormalities in the composition of the gut microbiota might contribute to the development of T2DM and that potential therapeutic strategies improving gut microbiota might provide beneficial effects for individuals with T2DM and age-related glucose intolerance.

20.
ACS Appl Mater Interfaces ; 11(45): 42086-42093, 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31637912

RESUMO

MXenes, synthesized from MAX, have emerged as new energy-storage materials for a good combination of metallic conductivity and rich surface chemistry. The reported MXenes are synthesized mostly from Al-based MAX. It is still a big challenge to synthesize MXenes from abundant Si-based MAX because of its strong Ti-Si bonds. Here, we report for the first time a high-energy ultrasonic cell-crushing extraction method to successfully prepare Ti3C2Tx MXenes from Si-based MAX using a single low-concentration etchant. This novel strategy for preparing MXenes has a high extraction efficiency and is a fast preparation process of less than 2 h for selective etching of Si. Furthermore, through the high-energy ball-milling technology, unique P-O-Ti bonded red phosphorus nanodot/Ti3C2Tx (PTCT) composites were successfully prepared, which enable superior electrochemical performance in lithium- and sodium-ion batteries because of the double-morphology structure, where the amorphous nano red phosphorus particles were strongly absorbed to Ti3C2Tx MXene sheets, facilitating the transport of alkali ions during cycling processes. This novel synthesis method of Ti3C2Tx MXenes from Si-based MAX and unique P-O-Ti bonded PTCT composites opens a new door for preparing high-performance MXene-based materials and facilitating the development of low-cost MXenes and other two-dimensional materials for next-generation energy storage.

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