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1.
Phytomedicine ; 65: 153091, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31654988

RESUMO

BACKGROUND: The development of rheumatoid arthritis (RA) is related to germinal center (GC) response and autoreactive T cells, which mediate adaptive immunity and play an important role in stimulating the production of autoantibodies and pro-inflammatory cytokines by B cells and macrophages. Total Glucosides of Paeony (TGP) has anti-inflammatory, immunomodulatory and analgesic effects and is widely used to treat RA. However, few studies investigated whether the therapeutic effect of TGP is associated with the inhibition of autoimmune response. PURPOSE: The aim of this study was to investigate the effects and mechanisms of TGP on RA. STUDY DESIGN: Type II collagen-induced arthritis (CIA) mouse model was used, and TGP and paeoniflorin were intragastrically treated. METHODS: DBA/1 mice were divided into 5 groups: control, model, positive drug (paeoniflorin) and high- and low-dose TGP group. After 21 days of intragastric administration, the pathological change, inflammation expression and molecular mechanism of each group of mice were detected by Micro-CT, histochemical analysis, ELLSA, Western blot, RT-qPCR and flow cytometry. RESULTS: Our study found that TGP treatment effectively improved inflammation and joint destruction in CIA mice. It reduced the production of serum IgG2a and pro-inflammatory cytokines, including serum interleukin (IL)-21, tumor necrosis factor (TNF)-α and IL-6, and the phosphorylation of NF-κB p65 and STAT3 in a dose-dependent manner. More importantly, TGP could suppress the frequency of germinal center B cells and Tfh cells in the spleen. CONCLUSION: TGP can not only improve symptoms, but also inhibit bone destruction. The therapeutic effect of TGP on CIA is mainly achieved by inhibiting spleen Tfh cell differentiation and GC formation through STAT3 signaling pathway.

2.
Artigo em Inglês | MEDLINE | ID: mdl-31586317

RESUMO

The nitrogen removal efficiency in constructed wetlands (CWs) was largely affected by the dissolved oxygen (DO). In this study, micro-aeration with different numbers of hollow fiber membrane modules (HFMEs) was adopted to increase the oxygen availability and improve the nitrogen removal efficiency in CWs under different air temperatures and different hydraulic retention time (HRT). Compared to the plant oxygen release (ROL) of wetland plants and traditional mechanical aeration, HFME increased the oxygen availability and enhanced the nitrogen removal efficiency in CWs. The COD and NH4+-N removal efficiencies increased with the increase of the HMFE. TN removal efficiency was increased by 8~16% after the application of HFME in CWs in the high-temperature stage. However, less HFME in CW-M1 realized the highest TN removal efficiency in low- and medium-temperature stages. At low temperature after 4-day HRT, the DO concentration respectively reached 6.25 mg L-1 and 3.25 mg L-1 in the upper zone and the bottom of CW-M1. The TN removal efficiencies in the upper zone of CW-M1 (60.69%) and the bottom of CW-M1 (64.98%) were all significantly higher than those in the upper zone of CK (35.98%) and the bottom of CK (39.9%). In addition, the microbial biomass and community analyses revealed that CW-M1 showed the most nitrifying bacteria and the best metabolic activity of bacteria. HEMF in CW-M1 also increased the nitrifying capacity from 0.12 to 0.46 mg kg-1 h-1. The application of HFME in CWs accelerated the nitrification process by enhancing nitrifying bacteria and less HFME realized the highest TN removal efficiency through nitrification-denitrification processes. Graphical abstract The application of hollow fiber membrane modules in CWs enhanced the pollutants (TN and COD) removal efficiency in the process of biological nitrification-denitrification and increased the number of nitrifying bacteria.

3.
Curr Top Med Chem ; 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31622219

RESUMO

In recent years, the successful implementation of human genome project has made people realize that genetic, environmental and lifestyle factors should be combined together to study cancer due to the complexity and various forms of the disease. The increasing availability and growth rate of 'big data' derived from various omics, opens a new window for study and therapy of cancer. In this paper, we will introduce the application of machine learning methods in handling cancer big data including the use of artificial neural networks, support vector machines, ensemble learning and naïve Bayes classifiers.

4.
Amyloid ; : 1-9, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31635489

RESUMO

Background: Amyloid light chain (AL) amyloidosis is characterized by tissue deposition of amyloid fibres derived from immunoglobulin that can lead to irreversible organ damage. Information about genomic profiles of AL amyloidosis is lacking. Methods: In this study, we adopted a two-step strategy to investigate the mutational profile of AL amyloidosis bone marrow plasma cells (PCs) and their clinical implications. In step one, whole-exome sequencing was performed in bone marrow PCs and paired with normal tissue from 10 AL amyloidosis patients, by which we identified 10 significantly mutated genes (SMGs). In step two, we constituted a targeted gene sequencing (TGS) panel covering the frequently mutated genes identified in step one, genes reported in prior AL amyloidosis studies, and known cancer driver mutations. Then, we analysed an expanded cohort of AL amyloidosis patients (N = 48) with this panel comprising 98 genes. Results: Four recurrent mutations were identified by TGS and verified by Sanger sequencing: ASB15 (c. 844 C > T), ASCC3 (c. 1595 A > G), HIST1H1E (c. 311 C > T) and KRAS (c. 35 G > A), among which the first three mutations were associated with inferior overall survival (OS). Additionally, we found that the number of mutations identified by the TGS panel of 98 genes could be a prognostic predictor for OS. Conclusions: In summary, we revealed genomic profiling in AL amyloidosis and found mutation profiles associated with OS.

5.
Otolaryngol Head Neck Surg ; : 194599819884889, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31635534

RESUMO

OBJECTIVE: To assess the long-term effects of velopharyngeal surgery on objective and subjective symptoms in patients with obstructive sleep apnea (OSA). STUDY DESIGN: Prospective cohort study. SETTING: University medical center. SUBJECTS AND METHODS: Eighty-six patients with OSA underwent velopharyngeal surgery, which consisted of revised uvulopalatopharyngoplasty with uvula preservation, with or without concomitant transpalatal advancement pharyngoplasty. The results from polysomnography and the Epworth Sleep Scale after 6 months and 5 years were compared with baseline. Baseline variables were compared between responders and nonresponders. RESULTS: Sixty-three patients were successfully followed up at the end of study. The surgical success rate after 6 months and 5 years was 66.67% (42 of 63) and 60.32% (38 of 63), respectively, with no significant difference (P = .459). The apnea-hypopnea index and Epworth Sleep Scale dramatically decreased from baseline after 6 months and 5 years in responders and nonresponders (P < .001 for all). As compared with nonresponders, the responders exhibited larger tonsil size, higher nocturnal lowest oxygen desaturation, lower CT90 (percentage of time with oxygen saturation <90%), and shorter MH (vertical distance between the lower edge of the mandible and hyoid in the midsagittal plane of computed tomography). Tonsil size and CT90 showed significant predictive value for surgery success (P < .001 for both). CONCLUSION: Velopharyngeal surgery was effective in improving nocturnal respiration and excessive daytime sleepiness in patients with OSA at 6-month and 5-year follow-up. Tonsil size and CT90 could be predictors for surgery responders.

6.
Cancer Gene Ther ; 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31664166

RESUMO

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) has been reported to kill a wide variety of tumor cells with minimal effects on normal cell. However, renal cell carcinoma (RCC) cells 786-0 and OS-RC-2 were resistant to TRAIL. The present study examines the potential of combining polyphenolic compound resveratrol (RES) with TRAIL. We found that RES can sensitize RCC cells to TRAIL-induced death. Electron microscopy analyses showed that RES plus TRAIL can induce both autophagy and apoptosis in RCC cells. It was proved that the apoptosis is caspase-dependent and the activation of caspase-8, caspase-9, and caspase-3 was involved in this process. Besides, we also found that XIAP expression was significantly inhibited after RES plus TRAIL treatment in RCC cells. Furthermore, a fiber-modified replication-deficient adenovirus Ad5/35-TRAIL was generated to test the synergistic effect of RES and TRAIL in vivo. Our data demonstrated that RES plus Ad5/35-TRAIL significantly inhibited RCC xenograft growth in nude mice. These results suggest the possibility of a new combination therapeutic leading to the improvement of RCC treatment.

7.
Bioresour Technol ; 294: 122189, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31569043

RESUMO

In this study, various modified agricultural wastes (modified canna leaves (MCL), modified rice straw (MRS) and modified peanut shells (MPS)) as solid carbon sources (SCSs) were used to remove nitrate in constructed wetlands (CWs). Then, modified SCSs combined with nZVI (SCSN) as co-electrons further enhanced both heterotrophic denitrification (HD) and autotrophic denitrification (AD) performance of CWs. The results showed that NO3--N removal efficiencies in CWs with SCSNs (75.3-91.1%) and in CWs with SCSs (63.3-65.5%) were significantly higher than that in CK-CW (47.0%). The presence of SCSs reduced the accumulation of NO2--N in CWs. Compared to the addition of SCSs, the addition of SCSNs decreased the effluent COD concentration in CWs, avoiding secondary pollution. In addition, the solid-phase denitrifiers Silanimonas and Thauera were enriched in MPS-CW. Thermomonas, an autotrophic denitrifying bacteria (ADB), and Azospira, a nitrate-reducing Fe (II) oxidation bacteria (NRFOB), exhibited high relative abundance in MPN-CW.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31629475

RESUMO

In our previous study, Oxysterol-binding protein-related protein 2 (OSBPL2) was first identified as a new deafness-causative gene contribute to non-syndromic hearing loss. However, the underlying mechanism of OSBPL2-induced hearing loss remains unknown. Here, we used hearing-specific cells and tissues OC-1 cells and zebrafish inner ear tissues as models to identify common transcriptome changes in genes and pathways in the absence of human OSBPL2 orthologues by RNA-seq analysis. In total, 2112 differentially expressed genes (DEGs) were identified between wild-type (WT) and Osbpl2-/- OC-1 cells, and 877 DEGs were identified between WT and osbpl2b-/- zebrafish inner ear tissues. Functional annotation implicated Osbpl2/osbpl2b in lipid metabolism, cell adhesion and the extracellular matrix in both OC-1 cells and zebrafish inner ear tissues. Protein-protein interaction (PPI) analysis indicated that Osbpl2/osbpl2b were also involved in ubiquitination. Further experiments showed that Osbpl2-/- OC-1 cells exhibited an abnormal focal adhesion morphology characterized by inhibited FAK activity and impaired cell adhesion. In conclusion, we identified novel pathways modulated by OSBPL2 orthologues, providing new insight into the mechanism of hearing loss induced by OSBPL2 deficiency.

10.
Leuk Res ; 86: 106226, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31541941

RESUMO

To summarize the clinical characteristics and prognostic factors of Chinese patients with systemic light chain amyloidosis with liver involvement. We retrospectively analyzed the clinical features and natural history data of 102 patients diagnosed with systemic light chain amyloidosis with liver involvement at Peking Union Medical College Hospital between March 2007 and May 2018. More than 95% of patients showed the involvement of other organs. Kidney and heart were the most frequently involved organs, accounting for 71.6% and 68.6% of cases, respectively. Hepatomegaly was the most frequently observed physical sign, accounting for 67.6% of cases. Elevated levels of alkaline phosphatase (ALP) and gamma-glutamyl transferase (GGT) were frequently observed, accounting for 85.3% and 88.2% of cases, respectively. A significantly better prognosis was observed in patients with normal total bilirubin levels, as compared with those with elevated levels of total bilirubin. Patients in the normal total bilirubin group showed a significantly better progression-free survival (PFS) (38 months) as compared the elevated total bilirubin group (4 months; P < 0.001). The median overall survival (OS) in the normal total bilirubin group was not reached compared with the elevated total bilirubin group (4 months, P < 0.001). Notably, the early death rate was significantly lower in the normal total bilirubin group as compared to the elevated total bilirubin group (14.5% vs 48.5%, P < 0.001). In conclusion, the elevation of total bilirubin indicated an early death and worse PFS and OS. Early diagnosis is therefore essential, and requires appropriate treatment and intensive care.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31478174

RESUMO

Phosphorus (P) characteristics in eutrophic lakes change during algal growth. Furthermore, algae have a significant relationship with the microbial communities of lake sediments. This study addressed the influence of algal growth and soluble reactive phosphorus (SRP) concentrations on P characteristics within the sediment-water-algal (SWA) system. Results indicated that the SWA system simulating a high algal bloom level (SWA-HAB) had a correspondingly high SRP concentration (258.9 µg L-1), and that algal growth promoted a high SRP concentration in the overlying water. The high SRP concentration in overlying water could support algal growth, resulting in a high chlorophyll a (Chl-a) concentration (285.23 mg L-1). During algal growth, the P release flux was high in sediments from the high-SRP SWA system, with the highest P release flux measured at 0.982 mg m-2 day-1. Furthermore, microbial community abundance had a significant relationship with Chl-a concentrations in overlying water (p < 0.05) and increases with algae growth.

12.
Opt Express ; 27(18): 25994-26013, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31510461

RESUMO

The classic Czerny-Turner spectrometer consists of a plane grating and two spherical mirrors. The optical path geometry adopted for incident and grating dispersed light is off-axis reflection, so the spherical collimating and focusing mirrors introduce coma and astigmatism. The conventional configuration is asymmetrical for coma automatic compensation, but suffers from astigmatism. We substitute the off-axis parabolic (OAP) surfaces for spherical surfaces of the collimating mirror and each sub-region of the focusing mirror, to achieve an aberration free configuration. The multiple OAP surfaces are then expanded and mixed, to construct a freeform surface integrating the collimating and focusing mirrors into a single element. Results show that a 0.1 nm spectral resolution is achieved over a bandwidth of 400 nm centered at 800 nm, in the designed spectrometer comprised of a plane grating and one freeform mirror. The construction method is advantageous to integrated optic design, and the resulting freeform mirror spectrometer is compact, and simplifies manufacture and alignment.

15.
Med Sci Monit ; 25: 6446-6453, 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31455757

RESUMO

BACKGROUND It has been reported that diabetic nephropathy and diabetic retinopathy are associated with each other through a shared pathophysiological mechanism. However, it is quite difficult to differentiate diabetic nephropathy from other glomerular diseases if diabetic retinopathy is absent in patients, and the only way to do this is to perform renal biopsies. The objective of this study was to test the hypothesis that diabetic nephropathy patients with and without diabetic retinopathy have different clinical and laboratory profiles. MATERIAL AND METHODS Medical records of type 2 diabetes mellitus patients with confirmed diabetic nephropathy were reviewed and analyzed with appropriate statistical modalities. Presence of arteriolar sclerosis of the carotid artery, abdominal aorta, upper extremities, and first-order aortic branches was regarded as a peripheral vascular disease. RESULTS Out of 217 type 2 diabetes mellitus patients with confirmed diabetic nephropathy, retinopathy was present in 106 (48.8%), while 111 (51.2%) had no evidence of retinopathy. About 45% of patients had pure diabetic nephropathy without any diagnosis of non-diabetic renal diseases, of which membranous nephropathy was most common. Diabetic nephropathy patients with retinopathy and those without retinopathy differed in duration of hypertension (p=0.041), serum creatinine (p=0.031), albumin (p=0.001), and erythrocyte sedimentation rate (p=0.001). Moreover, male preponderance (p<0.001), older age (p=0.033), and increased levels of albumin (p=0.033) were significantly associated with pure diabetic nephropathy without retinopathy. CONCLUSIONS Diabetic nephropathy patients with and without diabetic retinopathy have different clinical and laboratory profiles.

16.
J Contam Hydrol ; 226: 103537, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31408828

RESUMO

Hydraulic conditions of constructed wetlands (CWs) are crucial to pollutant removal and are influenced by factors such as influent loading rates, influent or effluent position or porous media size. The performance evaluation of CWs in real application, however, is difficult and a visualization analysis is difficult due to the black-box effect. In this paper, a nonopaque microcosmic horizontal subsurface flow constructed wetland (HSSFCW) reactor was built in the laboratory for an efficient and intuitive assessment of the influences of such parameters on the hydraulic performance of CWs. Chloride tracer tests were carried out to obtain parameters on hydraulic performance by considering hydraulic loading rates and different flow inlet-outlet configurations, while dye tracer tests were designed for the visualization of solute transport and diffusion. In parallel, an identical design of the HSSFCW reactor was modeled using the Visual MODFLOW (VM) software in order to detect the tracer movement and solute concentration field. Results show that the inflow rate and the inlet-outlet configuration have significant impacts on the hydraulic performance of a CW influencing RTD curve shape, flow path, dead zone distribution and hydraulic efficiency. The dead zone and flow path have been visualized and analyzed by comparing the dye tracer experiments of VM solute concentration field and particulate path-line tracking. In addition, the feasibility and reliability of the VM simulation has been verified. The application of VM in this study has been robust indicating a possible application for further investigations on the influencing factors of real CWs.

17.
Water Res ; 164: 114937, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31400593

RESUMO

Constructed wetlands coupled with a micro-electric field (CW-MEF) is a novel and efficient water treatment technology. The objective of this study was to investigate the mechanism and performance of trace metals (TMs) removal for CW-MEF systems during summer and winter. The mass distribution of TMs in plants and biofilms, physiological indices of wetland plants, and bacterial community structures on electrodes and in the rhizospheres were analyzed as well as to explore further the TM removal mechanism. Results show that the electric field intensities (EFI) of 100 and 200 mV cm-1 had a significantly promoting effect on TM removal. Maximum removal efficiencies for Cu, Zn, Cd, Co, Ni and Pb were 95.6, 80.1, 74.0, 67.1, 69.8 and 99.6%, respectively, in summer with a 5d-hydraulic retention time (HRT). An EFI of 100 mV cm-1 could alleviate the oxidative damage in plant cells by promoting the synthesis of reduced glutathione and an activity increase of catalase, thus increasing the phytoextraction for Cu, Zn and Cd. For biofilms, the MEF caused shifts in the bacterial community structures, and an EFI of 50 to 200 mV cm-1 significantly promoted the enrichment of Cu, Zn, Cd and Co by biofilms. Moreover, microorganisms related to TM tolerance and enrichment exhibited a high abundance with an EFI of 100 and 200 mV cm-1. It can be concluded that introducing MEF to CWs could intensify the TMs removal via the biological process and result in more efficient purification for TM-containing wastewater.

18.
Cell Death Dis ; 10(9): 627, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31427568

RESUMO

Oxysterol-binding protein like 2 (OSBPL2) was identified as a novel causal gene for autosomal dominant nonsyndromic hearing loss. However, the pathogenesis of OSBPL2 deficits in ADNSHL was still unclear. The function of OSBPL2 as a lipid-sensing regulator in multiple cellular processes suggested that OSBPL2 might play an important role in the regulation of cholesterol-homeostasis, which was essential for inner ear. In this study the potential roles of OSBPL2 in cholesterol biosynthesis and ROS production were investigated in Osbpl2-KO OC1 cells and osbpl2b-KO zebrafish. RNA-seq-based analysis suggested that OSBPL2 was implicated in cholesterol biosynthesis and AMPK signaling pathway. Furthermore, Osbpl2/osbpl2b-KO resulted in a reduction of AMPK activity and up-regulation of Srebp2/srebp2, Hmgcr/hmgcr and Hmgcs1/hmgcs1, key genes in the sterol biosynthetic pathway and associated with AMPK signaling. In addition, OSBPL2 was also found to interact with ATIC, key activator of AMPK. The levels of total cholesterol and ROS in OC1 cells or zebrafish inner ear were both increased in Osbpl2/osbpl2b-KO mutants and the mitochondrial damage was detected in Osbpl2-KO OC1 cells. This study uncovered the regulatory roles of OSBPL2 in cellular cholesterol biosynthesis and ROS production. These founds might contribute to the deep understanding of the pathogenesis of OSBPL2 mutation in ADNSHL.

19.
BMC Oral Health ; 19(1): 181, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395103

RESUMO

BACKGROUND: The purpose of this experiment was to assess the push out bond strength of Polydimethylsiloxane sealers (GuttaFlow 2 and GuttaFlow Bioseal by Colte'ne/Whaledent, Altstätten, Switzerland). AH Plus (Dentsply, DeTrey, Konstanz, Germany) was used as a reference material for comparison. METHODS: Thirty root slices were prepared from the middle third of 10 mandibular premolars. Each slice was 1 ± 0.1 mm thick. Three holes, 0.8 mm wide each, were drilled on the axial side of each root slice. These holes were subjected to standardized irrigations and then dried using paper points. Finally, for each root slice, each hole was filled with exactly one of the following three root canal sealers: AH Plus, GuttaFlow 2 and GuttaFlow Bioseal. After all the holes were filled in that way, the root slices were stored on top of phosphate-buffered saline solution (pH 7.2) soaked gauze for 7 days at the temperature of 37 degrees Celsius. Then, for each root canal sealer on a root slice, the universal testing machine was used to measure the push out bond strength. The differences in push out bond strengths between the three sealer samples were assessed using the Friedman test, while the paired comparisons were assessed using Wilcoxon signed rank test with Bonferroni correction. All statistical tests were two-tailed and the significance level was set at the 5%. RESULTS: According to the Friedman test the distributions of push out bond strengths of AH Plus, GuttaFlow 2 and GuttaFlow Bioseal were different (P < 0.05). Paired comparisons indicated that AH Plus had a significantly superior push out bond strength than GuttaFlow 2 and GuttaFlow Bioseal, while the push out bond strength of GuttaFlow Bioseal was significantly stronger than that of GuttaFlow 2 (P < 0.01). CONCLUSIONS: Based on these findings, AH Plus is a better root canal sealer than GuttaFlow 2 and GuttaFlow Bioseal.

20.
J Genet Genomics ; 46(8): 379-387, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31451425

RESUMO

Oxysterol binding protein like 2 (OSBPL2), an important regulator in cellular lipid metabolism and transport, was identified as a novel deafness-causal gene in our previous work. To resemble the phenotypic features of OSBPL2 mutation in animal models and elucidate the potential genotype-phenotype associations, the OSBPL2-disrupted Bama miniature (BM) pig model was constructed using CRISPR/Cas9-mediated gene editing, somatic cell nuclear transfer (SCNT) and embryo transplantation approaches, and then subjected to phenotypic characterization of auditory function and serum lipid profiles. The OSBPL2-disrupted pigs displayed progressive hearing loss (HL) with degeneration/apoptosis of cochlea hair cells (HCs) and morphological abnormalities in HC stereocilia, as well as hypercholesterolaemia. High-fat diet (HFD) feeding aggravated the development of HL and led to more severe hypercholesterolaemia. The dual phenotypes of progressive HL and hypercholesterolaemia resembled in OSBPL2-disrupted pigs confirmed the implication of OSBPL2 mutation in nonsydromic hearing loss (NSHL) and contributed to the potential linkage between auditory dysfunction and dyslipidaemia/hypercholesterolaemia.

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