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1.
Chemosphere ; 240: 124789, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31561157

RESUMO

Poly- and perfluorinated compounds (PFCs) may induce potential endocrine-disrupting hormonal effects. However, the molecular mechanism of the toxicology of PFCs remains unclear, and the insufficient information is available on the biological activities of PFCs at present. In this study, the cell-based reporter gene assays were used to determine the agonistic activity of PFCs on the human pregnane X receptor (hPXR). The heuristic method combined with best subset modeling (HM-BSM) based on Dragon descriptors and comparative similarity indices analysis (CoMSIA) were employed to build classical quantitative structure-activity relationship (QSAR) and three-dimensional QSAR models, respectively. The applicability domain (AD) of the classical QSAR model was assessed. Both the HM-BSM and CoMSIA approaches demonstrated good robustness, predictive ability, and mechanistic interpretability. The r2 and leave-one-out cross-validation squared correlated coefficient (q2LOO) values were 0.872 and 0.759 for the HM-BSM, and 0.976 and 0.751 for the CoMSIA model, respectively. The hPXR agonistic activity of the PFCs predicted by the built HM-BSM and CoMSIA agreed well with experimental activity, with root mean square error (RMSE) values of 0.0803 and 0.117, respectively, and external validation squared correlated coefficients (q2EXT) of 0.972 and 0.932, respectively. The hPXR agonistic activity of PFCs was related to their molecular polarizability, charge and atomic mass. Hydrogen bonding and hydrophobic interactions constituted the primary intermolecular forces between PFCs and the hPXR. The developed models were used to screen the PFCs with high hPXR agonistic activity.

2.
J Nanosci Nanotechnol ; 20(2): 900-908, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31383085

RESUMO

A series of polyurethane hydrogel and polyurethane thermoplastic elastomer composite based separation membranes were successfully prepared via wet phase inversion method. The morphology, chemical structure, phase transition temperature and crystallinity of the polyurethane (PU) membranes were characterized by SEM, FTIR, DSC, and XRD, respectively. The SEM observation showed that the PU membranes exhibited irregular porous structure on the surface and path of the hole was flexural and asymmetrical in cross-section. The FTIR analysis demonstrated that thermalsensitive groups and pH-sensitive components (-N(CH3)-) were incorporated into the PU network. The DSC experiment and XRD experiment showed that the regular arrangement of PU network was destroyed partly due to the introduction of polyurethane thermoplastic elastomer. The equilibrium swelling ratio (ESR) and water flux (J) for PU membranes clearly decreased and increased with functional groups and sophisticated structure of PU membranes, respectively. In addition, the permeation experiments indicated that the permeation percentage (P) of the glycine was strongly affected by the external temperature and pH value.

3.
Talanta ; 207: 120294, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31594563

RESUMO

Dual-functional nanosensors based on small molecule regulation can be widely used due to their simplicity, high sensitivity and selectivity. Herein, glutathione (GSH) calibrated dual-functional system for GSH and cadmium ions (Cd2+) detection based on fluorescence resonance energy transfer (FRET) between NH2-NaYF4:Yb,Er/NaYF4@SiO2 upconversion nanoparticles (UCNPs) and gold nanoparticles (AuNPs) is designed. Unmodified AuNPs are easy to aggregate in high-salt solution and thereby quenching the red emission of UCNPs. The presence of GSH prevents the aggregation of AuNPs, so GSH can be detected by the changes in the color of solution and the recovery of red emission of UCNPs. However, Cd2+ can interact with GSH, which makes AuNPs easy to aggregate, resulting in a gradual decrease in red emission of UCNPs. The fluorescence response of the system is linear with the concentrations of GSH and Cd2+ in a wide range of concentrations, with low detection limits of 0.016 µM and 0.059 µM, respectively. Furthermore, the nanosensor demonstrates high selectivity for GSH and Cd2+ detection and can be applied for the detection of GSH in human plasma and Cd2+ in drinking water.

4.
MAbs ; 12(1): 1685814, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31774346

RESUMO

Therapeutic monoclonal antibodies (mAbs) are commonly administered to patients through intravenous (IV) infusion, which involves diluting the medication into an infusion solution (e.g., saline and 5% dextrose). Using the wrong diluent can cause product aggregation, which may compromise patient safety. We and others have shown that Herceptin® (trastuzumab) and Avastin® (bevacizumab) undergo rapid aggregation upon mixing with dextrose and human plasma in vitro. In this study, we evaluated the compatibility of a panel of 11 therapeutic mAbs with dextrose or saline and human serum. These mAbs were randomly selected for their distinct formulations and IgG isotypes (IgG1, IgG2, IgG4, and Fc-fusion protein). All the mAbs appeared to be compatible with saline and human serum. However, mAbs that were formulated at acidic pH (≤ 6.5) exclusively formed insoluble aggregates upon mixing with dextrose and serum. Such aggregation was not detected for the mAbs that are at neutral pH (7.2-7.5) or in buffers containing sodium chloride. Mass spectrometric analysis revealed that the insoluble aggregates were composed of mAb molecules and several serum proteins (e.g., complement proteins, apolipoprotein, fibronectin) that are characterized by an isoelectric point of pH 5.4-6.7. At proximate pH to the isoelectric point values, those abundant serum proteins appeared to undergo isoelectric precipitation with mAb molecules. Our observations highlight a potential risk of protein aggregation at the blood-IV interface if a diluent is incompatible with a specific mAb formulation. This information has implications in guiding the design of product formulations and the selection of the right diluent for intravenous infusion of therapeutic mAbs.Abbreviations: ADC: antibody-drug conjugate; D5W: 5% dextrose in water; IM: intramuscular; IV: intravenous; LC-MS/MS: liquid chromatography-tandem mass spectrometry; mAb: monoclonal antibody; SC: subcutaneous; pI: isoelectric point.

5.
Arch Gerontol Geriatr ; 86: 103965, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31683176

RESUMO

BACKGROUND: Centenarians are the fastest growing population worldwide. However, this group has been less studied in developing countries. Contemporary centenarians in China have experienced many ups and downs due to historical reasons, which may have resulted in a population with different characteristics from those in other countries. This study aimed to investigate the current sociodemographic characteristics, health profiles, and social relationships of Chinese centenarians. METHODS: We conducted face-to-face surveys in April 2017 with centenarian residents in Suixi County, the first "International Healthy Longevity Area" in China. A total of 100 centenarians were involved, including 67 females and 33 males. Information for socioeconomic and demographics characteristics, quality of life (physical, cognitive, and psychological function), and social support and relationships was collected. Sex differences in each measure were examined. RESULTS: We find that good self-reported health, good life satisfaction, intact memory function, independence, and unsatisfied healthcare needs were reported by 24.4%, 45.9%, 31.6%, 46.3%, and 33.4% of the respondents respectively. Subjective symptoms among males were less prevalent (p < 0.05). There were no statistical significant sex differences in cognitive and psychological function. The major source of care provision has been family. Generally, the centenarians had intimate relationships within families but maintained distant relationships with friends and communities. CONCLUSION: Our results bring attention to family-based care to provide informal care, and health education to promote healthy behaviors and healthcare utilization, for the oldest-old in China. The findings also imply a crucial role of good relationships with family in exceptional longevity.

6.
J Cell Biochem ; 121(1): 49-62, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31571264

RESUMO

Acute coronary syndrome (ACS) is characterized by atherosclerotic plaque rupture with a high incidence of recurrent ischemic events. Several microRNAs are found to be aberrantly expressed in atherosclerotic plaques. This study aims to investigate the effects of microRNA-9 (miR-9) on vulnerable atherosclerotic plaque and vascular remodeling in ACS and underlying mechanisms. Microarray-based gene expression profiling was used to identify differentially expressed genes related to ACS and regulatory miRNAs. Oxidized low-density lipoprotein (lectin-like) receptor 1 (OLR1) was identified to be aberrantly activated in ACS and regulated by miR-9. OLR1 was verified as a target gene of miR-9 by bioinformatics prediction and dual luciferase reporter gene assay. The atherosclerotic models were induced in ApoE-/- mice, in which the agomir or antagomir of miR-9, or small interfering RNA (siRNA) against OLR1 were separately introduced. Serum lipid levels and expression of vascular remodeling and inflammatory response-related factors were determined, respectively. On the basis of the obtained results, in the atherosclerosis mice treated with the agomir of miR-9 and siRNA against OLR1, the p38-mitogen-activated protein kinase (p38MAPK) pathway was inhibited; levels of triglyceride, total cholesterol, low-density lipoprotein cholesterol, tumor necrosis factor-α, interleukin-6, and vascular endothelial growth factor were reduced, but the high-density lipoprotein cholesterol level was increased, along with decreased vulnerable atherosclerotic plaque area and enhanced vascular remodeling. Taken together, these findings suggested an inhibitory role miR-9 acts in the formation of vulnerable atherosclerotic plaques in ACS mice, along with a promoted vascular remodeling, via a negative feedback regulation of OLR1-mediated p38MAPK pathway.

7.
Mater Sci Eng C Mater Biol Appl ; 107: 110346, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31761193

RESUMO

In the current study, we developed interpolymer-complex structures composed of hydroxypropyl methylcellulose (HPMC) and chitosan knitted with d-α-tocopherol polyethylene glycol succinate (TPGS) to establish oral nanoparticle delivery systems that could keep the drug dose from releasing into the gastrointestinal tract for at least 6 h. Two kinds of nanoparticle formations based on the so-called conjugate-by-conjugate strategy were introduced in the study. In the first conjugate-by-conjugate structured nanoparticle formation, TPGS was conjugated with an HPMC-chitosan conjugate, followed by the drug loading process. In the second approach, the drug was loaded with TPGS directly and subsequently conjugated with the HPMC-chitosan conjugate. Beneficially, polyvinyl alcohol could act not only as a stabilizing agent but also as a crosslinking agent for the nanoparticles. This study created newly modified structures of HPMC and chitosan, altering their physicochemical properties that could then retard drug release. The nanoparticles were cytotoxic towards MDA-MB-231 breast cancer cells when docetaxel was loaded in the nanoparticles, particularly the nanoparticles produced in the second approach, demonstrating their ability to kill cancerous cells and their potential for further applications in cancer therapy. Additionally, when Caco-2 cells were used as an absorption model in a transport study, the nanoparticles in the second approach showed their capacity to increase drug permeability across the monolayers of Caco-2 cells compared to the free-drug solution. This study also illustrated the enhanced uptake of the nanoparticles by the Caco-2 cells, implying enhanced absorption through the intestine. Therefore, these oral nanoparticles can be considered for delivery systems of agents that are sensitive to the gastrointestinal tract so that they can be transported across the epithelial cells to the bloodstream to deliver the loading cargo at an optimal concentration.

8.
Food Chem ; 306: 125593, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31610327

RESUMO

The heat-induced aggregation of edible proteins has been regarded as one of the critical challenges for their application in protein-enriched beverages. Therefore, the formulation of thermal stable proteins to improve the stability of these beverages upon heating is highly desired. In this study, soy proteins (SPs) with enhanced heat stability were obtained by low-concentration-preheating (LCPH). Results from reheating of the above samples showed that pretreatment of SPs at low concentrations (≤1.0%, w/v) increased their resistance against aggregation. Additionally, when the suspensions of the particles were reheated at 10% (w/v) protein concentration, no gelation was found for samples prepared by LCPH, indicating collapsed protein-protein interactions, whereas gelled suspensions were obtained for native SPs and samples prepared by preheating at higher protein concentrations (≥2.0%, w/v). Furthermore, suspensions of particles prepared at lower protein concentration showed lower viscosities and higher flow behavior index values before and after reheat treatment. These findings highlighted that LCPH would provide fundamental information on the application of SPs in high protein beverages.

9.
Gene ; 722: 144101, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31479714

RESUMO

The catadromous species, eels, invariably exposed to variable Ca2+ concentrations circumstance i.e., lagoon or ocean. They need to maintain Ca2+ homeostasis by exchanging Ca2+ under different culture conditions. To understand the effects of environmental Ca2+ to fish, three types of genes coding for voltage-dependent L-type calcium channels (cacnb1, 2, 3) were cloned by screening an A. marmorata cDNA library. Tissue distribution analysis of Western blot showed that Cacnb1, 2, 3 had a significantly high expression in gill; while mRNA results showed the expressions of cacnb1 and cacnb3 were predominated in skin tissue but only cacnb2 was expressed in intestine. Serum osmolality and Ca2+ concentrations of A.marmorata were increased in a high calcium environment while reduced in a low calcium environment within 7 days; however, they were not significantly different among Ca2+ treatments after the eels were acclimated for 7 days. We also examined the influence of ambient Ca2+ levels on cacnbs expression of eels. With the increasing of exposure time, mRNA and protein expressions of cacnb1 were up-regulated in high level of Ca2+ (10 mM) and down-regulated in deficient Ca2+ (0 mM) compared to the control Ca2+ (2 mM). However, the opposite results were observed in cacnb2 and cacnb3. Notably, the cacnb2 expression was not significant different among Ca2+ treatments on day 7. Our study provided the insightful evidence that cacnbs play important roles in maintaining Ca2+ homeostasis of fish.


Assuntos
Anguilla/metabolismo , Canais de Cálcio Tipo L/metabolismo , Cálcio/fisiologia , Aclimatação , Anguilla/sangue , Anguilla/genética , Animais , Cálcio/sangue , Canais de Cálcio Tipo L/química , Canais de Cálcio Tipo L/genética , Clonagem Molecular , Brânquias/metabolismo , Concentração Osmolar , RNA Mensageiro/metabolismo , Distribuição Tecidual
10.
Artigo em Inglês | MEDLINE | ID: mdl-31785250

RESUMO

PURPOSE: Postoperative pain is a negative factor that seriously affects a surgical patient's rehabilitation. We investigated whether nalbuphine provides superior postoperative analgesia in orthognathic surgery compared with sufentanil and whether the superior analgesia is achieved by the regulation of inflammatory and oxidative stress. PATIENTS AND METHODS: In the present randomized, double-blind, controlled clinical trial, 60 patients scheduled to undergo orthognathic surgery were randomized to receive 2.5 µg/kg of sufentanil (group S) or 2 mg/kg of nalbuphine (group N) for postoperative controlled intravenous analgesia. The primary outcome variable was the visual analog scale (VAS) score. The secondary outcome variables included the sedation score (Ramsay score) and plasma levels of inflammation factors, including tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and oxidant stress factors, including malondialdehyde (MDA) and superoxide dismutase (SOD). RESULTS: The VAS scores of group N was significantly lower than those of group S, and the Ramsay scores for group N was greater. The plasma levels of TNF-α, IL-6, and MDA for group N were significantly lower than those for group S, and the SOD levels were greater than those for group S. Furthermore, the VAS scores correlated positively with the plasma levels of TNF-α, IL-6, and MDA and correlated negatively with the SOD levels. CONCLUSIONS: Nalbuphine offers better postoperative analgesia and sedation after orthognathic surgery. Nalbuphine also seems to provide superior postoperative analgesia by reducing inflammatory and oxidative stress.

11.
Free Radic Biol Med ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31785331

RESUMO

The liver is the most important metabolic and detoxifying organ in the human body, and liver damage can seriously affect bodily function and potentially be life threatening. Accumulating evidence suggests that maresin 1 (MaR1) exhibits protective and anti-inflammatory effects in some diseases, such as pneumonia and colitis; however, its role in acute hepatitis remains unclear. Here, we established a concanavalin A (ConA)-induced acute liver-injury mouse model to determine whether MaR1 administration can attenuate liver damage. Our results indicate that MaR1 confers protective effects against ConA-induced acute liver injury, improves liver function and survival, and reduces histopathological damage. Additionally, MaR1 attenuated the inflammatory response and reduced hepatocyte apoptosis while increasing mouse macrophage apoptosis and markedly decreasing levels of reactive oxygen species (ROS) in macrophages. We also found that MaR1 significantly inhibited ConA-induced activation of the nuclear factor-kappaB (NF-κB) pathway. This work will contribute to a better understanding of acute liver injury (ALI) and advancement towards its treatment.

12.
Org Lett ; 2019 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-31794231

RESUMO

A general approach for the synthesis of 3-(iso)quinolinyl 4-chromenones and 3-(iso)quinolinyl 4-quinolones from (iso)quinoline N-oxides and ynones under metal-free conditions was developed. The reaction of (iso)quinoline N-oxide with the electron-deficient alkyne first generated an (iso)quinolinyl ß-diketone intermediate, which then underwent an intramolecular dehydration, affording 3-(iso)quinolinyl 4-chromenones and 3-(iso)quinolinyl 4-quinolones.

13.
DNA Cell Biol ; 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31794266

RESUMO

Septic cardiomyopathy (SC) is a rare and harmful cardiovascular disease with decreased left ventricular (LV) output and multiple organ failure, which poses a serious threat to human life. Despite the advances in SC, its diagnostic basis and treatment methods are limited, and the specific diagnostic biomarkers and its candidate regulatory targets have not yet been fully established. In this study, the GSE79962 gene expression profile was retrieved, with 20 patients with SC and 11 healthy donors as control. Weighted gene coexpression network analysis (WGCNA) was employed to investigate gene modules that were strongly correlated with clinical phenotypes. Blue module was found to be most significantly related to SC. Moreover, Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the coexpression genes in blue module and showed that it was associated with metabolic pathways, oxidative phosphorylation, and cardiac muscle contraction. Furthermore, a total of 10 hub genes NDUFB5, TIMMDC1, VDAC3, COQ10A, MRPL16 (mitochondrial ribosomal protein L16), C3orf43, TMEM182, DLAT, NDUFA8, and PDHB (pyruvate dehydrogenase E1 beta subunit) in the blue module were identified at transcriptional level and further validated at translational level in myocardium of an lipopolysaccharide-induced septic cardiac dysfunction mouse model. Overall, the results of quantitative real-time polymerase chain reaction were consistent with most of the microarray analysis results. Intriguingly, we observed that the highest change was NDUFB5, TIMMDC1, and VDAC3. These identified and validated genes provided references that would advance the understanding of molecular mechanisms of SC. Taken together, using WGCNA, the hub genes NDUFB5, TIMMDC1, and VDAC3 might serve as potential biomarkers for diagnosis and/or therapeutic targets for precise treatment of SC in the future.

14.
Water Res ; 170: 115329, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31785560

RESUMO

The growing amount of sewage sludge from wastewater treatment plant is an emerging challenge in China. The efficient anaerobic digestion of sludge filtrate generated from hydrothermally pretreated sewage sludge can promote the disposal of sewage sludge. Herein, a pilot-scale anaerobic baffled reactor (ABR) assisted by symbionts of short chain fatty acid-oxidation syntrophs (SFAS) and exoelectrogens was developed to improve its stability and efficiency for filtrate treatment. The results demonstrated that the symbionts of exoelectrogens and SFAS, which were enriched by introduction of electrodes in the ABR system, promoted the degradation of butyric, propionic and acetic acids. Therefore, the COD removal efficiency increased from 74.1% to 86.6% and the methane content increased from 81.5% to 92.2% with methane production rising from 241 to 282 mL/g CODremoved. Furthermore, the economic evaluation indicated that the energy consumption of electrodes was 0.600 kWh/m3 of sludge filtrate, the net energy profited from increased methane was 2.344 kWh/m3 of sludge filtrate. These results confirmed that the ABR system assisted by symbionts of SFAS and exoelectrogens was feasible for treatment of sludge filtrate in terms of both technical and economic level through pilot-scale verification.

15.
Leuk Res ; 88: 106283, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31790983

RESUMO

Minimal residual disease (MRD) negativity is a key prognostic indicator of outcome in acute lymphocytic leukemia. In the INO-VATE trial (clinicaltrials.gov identifier: NCT01564784), patients with relapsed/refractory acute lymphocytic leukemia who received inotuzumab versus standard chemotherapy achieved greater remission and MRD-negativity rates as well as improved overall survival: hazard ratio 0.75, one-sided P = 0.0105. The current analysis assessed the prognostic value of MRD negativity at the end of inotuzumab treatment. All patients who received inotuzumab (n = 164) were included. Among patients with complete remission/complete remission with incomplete hematologic response (CR/CRi; n = 121), MRD-negative status (by multiparametric flow cytometry) was defined as <1 × 10-4 blasts/nucleated cells. MRD negativity was achieved in 76 patients at the end of treatment. Compared with MRD-positive, MRD-negative status with CR/CRi was associated with significantly improved overall survival and progression-free survival, respectively: hazard ratio (97.5% confidence interval; one-sided P-value) 0.512 (97.5% CI [0.313-0.835]; P = 0.0009) and 0.423 (97.5% CI [0.256-0.699]; P < 0.0001). Median overall survival was 14.1 versus 7.2 months, in the MRD-negative versus MRD-positive groups. Patients in first salvage who achieved MRD negativity at the end of treatment experienced significantly improved survival versus that seen in MRD-positive patients, particularly for those patients who proceeded to stem cell transplant. Among patients with relapsed/refractory acute lymphocytic leukemia who received inotuzumab, those with MRD-negative CR/CRi had the best survival outcomes.

16.
Chem Commun (Camb) ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31803872

RESUMO

The capacity degradation mechanism of a spent LiFePO4 (LFP) cathode was investigated systematically and the occurrence of FePO4 in the cathode due to loss of Li+ was found to be mainly responsible for the short cycle life of LFP batteries. Given this, an easy, low-cost, and green cathode regeneration method was proposed. This work provides a new perspective for the recycling of spent batteries.

17.
Anat Rec (Hoboken) ; 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31804026

RESUMO

The Lower Jurassic Lufeng Formation in Yunnan Province of southwestern China provides one of the most abundant records of sauropodomorphs in the world. However, most of them have not been fully described. Xingxiulong chengi is among the most complete non-sauropodan sauropodomorphs ever discovered from Lufeng Formation and is represented by three partial skeletons. Here, we provide a detailed osteological description of its axial skeleton, including both the cranial and postcranial elements, and compare its anatomy with that of other known non-sauropodan sauropodomorphs. In general, the cranium of Xingxiulong is more similar to those of more basal sauropodomorphs than to sauropodiforms, as evidenced by features such as an only slightly concave dorsal margin of the postorbital, a caudally placed rostral margin of the infratemporal fenestra not extending below the orbit, and long and slender basipterygoid processes divergent from each other at an angle of approximately 80 degrees. However, its postcranial axial skeleton possesses some unique or relatively derived features among basal sauropodomorphs, such as four sacral vertebrae and caudal dorsal vertebrae with laterally expanded neural spine tables. This provides future workers with a reassessment of non-sauropodan sauropodomorphs through the lens of Xingxiulong chengi, which will serve to increase our knowledge on the anatomy, phylogeny, and furthermore, evolution of sauropodomorph dinosaurs. Anat Rec, 2019. © 2019 American Association for Anatomy.

18.
BMC Neurol ; 19(1): 266, 2019 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-31684908

RESUMO

BACKGROUND: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) is an inflammatory disorder in the central nervous system (CNS) with distinct clinical, radiological, and pathological characteristics. The pathophysiology of CLIPPERS still remains unclear. Because a few cases about lymphoma mimicking the manifestations of CLIPPERS were reported and the prognosis of lymphoma is much worse, early identification of lymphoma is very important. CASE PRESENTATION: A 31-year-old woman was admitted with 3 months' history of diplopia, dizziness, gait ataxia, and right facial numbness. The diagnosis of CLIPPERS was established based on the finding of punctate enhancing lesions in the cerebellum, thalamus, pons, medulla, and midbrain region in magnetic resonance imaging (MRI), together with the favorable clinical and radiological responses to corticosteroids. However, she was diagnosed as peripheral T cell lymphoma, not otherwise specified (PTCL-NOS) by the pulmonary nodular and the skin biopsy almost 10 years later, and she got complete remission within 1 year after chemotherapy. CONCLUSION: We report the first case of CLIPPERS developing PTCL-NOS. This case proposes that when brain biopsy was difficult to achieve, biopsies in extra-cerebral lesions under the assisting examination of positron emission tomography-computed tomography (PET-CT) can be helpful in further identification.

19.
Blood ; 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31697807

RESUMO

Altered metabolism fuels two hallmark properties of cancer cells, unlimited proliferation and differentiation blockade. AMP-activated protein kinase (AMPK) is a master regulator of bioenergetics crucial for glucose metabolism in acute myeloid leukemia (AML) and its inhibition delays leukemogenesis, but whether the metabolic function of AMPK alters the AML epigenome remains unknown. Here, we demonstrate that AMPK maintains the epigenome of MLL-rearranged AML by linking acetyl-CoA homeostasis to BET protein recruitment to chromatin. AMPK deletion reduced acetyl-CoA and histone acetylation, displacing BET proteins from chromatin in leukemia-initiating cells. In both mouse and patient-derived xenograft AML models, treating with AMPK and BET inhibitors synergistically suppressed AML. Our results provide a therapeutic rationale to target AMPK and BET for AML therapy.

20.
J Hazard Mater ; : 121506, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31699487

RESUMO

Congo red (CR) is a typical and widely used azo dye in industries. It possesses the serious threat to ecosystem and public for its indiscriminate discharge. Microbial flocculant (MBF) with various functional groups is a potential flocculant applied in dyeing wastewater treatment, and it has the advantages of high treatment efficiency, biodegradability and non-toxicity. In this study, the functional groups, amino group, ammonium group and acyloxy group, were grafted onto MBF to further improve its thermal stability, solubility and performance. Grafting copolymerization occurred at the amino group of MBF was confirmed by XPS. Polyaluminum silicate (PSA) and self-prepared functional microbial flocculant, MBF-g-P(AM-DAC), played different roles in CR wastewater treatment. PSA contributed to charge neutralization, but its yielded flocs were small. On the contrary, MBF-g-P(AM-DAC) possessed weak charge neutralization but big flocs. Its settlement efficiency has significantly improved. The unsaturated active sites on MBF-g-P(AM-DAC) and its flocs contributed to the adsorption of CR in terms of high surface area and adsorption capacity of the flocs. Physical adsorption and chemical adsorption were both discovered in the treatment.

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