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1.
J Thromb Haemost ; 19(4): 1038-1048, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33534149

RESUMO

BACKGROUND: High incidence of asymptomatic venous thromboembolism (VTE) has been observed in severe COVID-19 patients, but the characteristics of symptomatic VTE in general COVID-19 patients have not been described. OBJECTIVES: To comprehensively explore the prevalence and reliable risk prediction for VTE in COVID-19 patients. METHODS/RESULTS: This retrospective study enrolled all COVID-19 patients with a subsequent VTE in 16 centers in China from January 1 to March 31, 2020. A total of 2779 patients were confirmed with COVID-19. In comparison to 23,434 non-COVID-19 medical inpatients, the odds ratios (ORs) for developing symptomatic VTE in severe and non-severe hospitalized COVID-19 patients were 5.94 (95% confidence interval [CI] 3.91-10.09) and 2.79 (95% CI 1.43-5.60), respectively. When 104 VTE cases and 208 non-VTE cases were compared, pulmonary embolism cases had a higher rate for in-hospital death (OR 6.74, 95% CI 2.18-20.81). VTE developed at a median of 21 days (interquartile range 13.25-31) since onset. Independent factors for VTE were advancing age, cancer, longer interval from symptom onset to admission, lower fibrinogen and higher D-dimer on admission, and D-dimer increment (DI) ≥1.5-fold; of these, DI ≥1.5-fold had the most significant association (OR 14.18, 95% CI 6.25-32.18, p = 2.23 × 10-10 ). A novel model consisting of three simple coagulation variables (fibrinogen and D-dimer levels on admission, and DI ≥1.5-fold) showed good prediction for symptomatic VTE (area under the curve 0.865, 95% CI 0.822-0.907, sensitivity 0.930, specificity 0.710). CONCLUSIONS: There is an excess risk of VTE in hospitalized COVID-19 patients. This novel model can aid early identification of patients who are at high risk for VTE.

2.
Huan Jing Ke Xue ; 42(1): 136-146, 2021 Jan 08.
Artigo em Chinês | MEDLINE | ID: mdl-33372465

RESUMO

Solid phase extraction (SPE) and high-performance liquid chromatography-mass spectrometry (HPLC-MS) were used to detect and analyze the distribution of 10 antibiotics including sulfonamides, fluoroquinolones, and macrolides in the Harbin section of Songhua River basin and Ashe River, a tributary of Songhua River. The correlation between the antibiotic concentration and water quality indexes was analyzed and the ecological risks were evaluated. The results showed that only six antibiotics were detected in the entry section of Harbin city on the Songhua River and the concentration was relatively low. However, nine antibiotics were detected in the exit section and only sulfamethazine (SM1) was not detected. The concentrations of macrolide antibiotics increased most significantly, followed by those of sulfonamides and fluoroquinolones. The inflow of three tributaries in Harbin city was the direct cause of the increase in antibiotic concentration in the Songhua River. Only sulfapyridine (SMPD) was not detected in the upper section of Ashe River. Ten antibiotics were detected in the section where the Ashe River enters the Songhua River. The other nine antibiotics were the highest except norfloxacin (NOR). Wastewater discharged from four sewage treatment plants along Ashe River is an important factor affecting the concentration of antibiotics in the Ashe River. Correlation analysis shows that three kinds of antibiotics in the Songhua River have certain positive correlations with ammonia nitrogen, total phosphorus, and total organic carbon. There is a significant positive correlation between the three kinds of antibiotics and ammonia nitrogen and total phosphorus in the Ashe River system, indicating that the water quality indexes of the Harbin section of Songhua River and Ashe River are closely related to their antibiotic concentrations. The results of ecological risk assessment showed that macrolide antibiotics in the Harbin section of Songhua and Ashe Rivers had certain ecological risks.


Assuntos
Rios , Poluentes Químicos da Água , Antibacterianos , China , Monitoramento Ambiental , Medição de Risco , Poluentes Químicos da Água/análise
3.
Nanotechnology ; 2020 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-33373982

RESUMO

Magnetotransport properties of a hybrid InSe/monolayer graphene on SiC system are systematically studied. Compared to those of its bare graphene counterpart, in InSe/graphene, we can effectively modify the carrier density, mobility, effective mass, and electron-electron interactions enhanced by weak disorder. We show that in bare graphene and hybrid InSe/graphene systems, the logarithmic temperature (lnT) dependence of the Hall slopeRH=δRxy/δB=δRxy/δB can be used to probe electron-electron interaction effects at various temperatures even when the measured resistivity does not show a lnT dependence due to strong electron-phonon scattering. Nevertheless, one needs to be certain that the change ofRHis not caused by an increase of the carrier density by checking the magnetic field position of the longitudinal resistivity minimum at different temperatures. Given the current challenges in gating graphene on SiC with a suitable dielectric layer, our results suggest that capping a van der Waals material on graphene is an effective way to modify the electronic properties of monolayer graphene on SiC.

4.
Phys Chem Chem Phys ; 22(46): 27206-27213, 2020 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-33226035

RESUMO

The tritium release behavior of the Li2TiO3 crystal has become an important index to evaluate its comprehensive performance as a solid breeder material in nuclear fusion reactors. The tritium diffusion on the surface (surface diffusion) and diffusion from the inside to the surface (hopping diffusion) in Li2TiO3 crystals with a 1/3-Li(001) surface are systematically investigated by the first-principles method. Possible adsorption sites, diffusion pathways and energy barriers of surface diffusion and hopping diffusion have been calculated and analyzed, respectively. Tritium atoms are found to diffuse preferentially along the [100] direction on the surface and two equivalent pathways across the surface were identified. The obtained activation energies are about 0.50 eV for surface diffusion and 1.56 eV for hopping diffusion. The local density of states and Bader charge for typical surface diffusion and hopping diffusion pathways are calculated and analyzed. The results reveal that the tritium (T) atom bonds with neighboring oxygen (O) atoms during the surface diffusion, while the T-O interaction is significantly weakened in the hopping diffusion which results in the higher activation energy than that of surface diffusion. In combination with our previous work, a complete tritium diffusion model for the Li2TiO3 crystal is proposed and the corresponding tritium diffusion coefficients are obtained. Our obtained activation energies are in the same range as previous experimental data and could provide theoretical support for the future related experiments.

5.
Medicine (Baltimore) ; 99(40): e22310, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019406

RESUMO

Immunoglobulin A nephropathy (IgAN) is a major cause of secondary hypertension (HT) of renal origin - a significant prognostic factor of IgAN. In children, similar to HT, prehypertension (pre-HT) is becoming a significant health issue. However, the role of secondary HT and pre-HT (HT/pre-HT) in the progression of pediatric IgAN remains unclear. We investigated the effects of HT/pre-HT on prognosis and its determinants as well as their correlation with clinicopathological parameters to identify more effective therapeutic targets.This single-center retrospective study compared clinicopathological features and treatment outcomes between patients with and without HT/pre-HT in 108 children with IgAN. Independent risk factors for HT/pre-HT were evaluated; segmental glomerulosclerosis was a significant variable, whose relationship with clinicopathological parameters was analyzed.Clinical outcomes of patients with and without HT/pre-HT differed considerably (P = .006) on ≥6 months follow-up. Patients with HT/pre-HT reached complete remission less frequently than those without HT/pre-HT (P = .014). Age, serum creatinine, prothrombin time, and segmental glomerulosclerosis or adhesion were independent risk factors for HT/pre-HT in pediatric IgAN (P = .012, P = .017, P = .002, and P = .016, respectively). Segmental glomerulosclerosis or adhesion was most closely associated with glomerular crescents (r = 0.456, P < .01), followed by Lees grades (r = 0.454, P < .01), renal arteriolar wall thickening (r = 0.337, P < .01), and endocapillary hypercellularity (r = 0.306, P = .001). The intensity of IgA deposits, an important marker of pathogenetic activity in IgAN, was significantly associated with the intensity and location of fibrinogen deposits (intensity: r = 0.291, P = .002; location: r = 0.275, P = .004).HT/pre-HT in pediatric IgAN patients is an important modifiable factor. A relationship is observed between HT/pre-HT and its determinants, especially segmental glomerulosclerosis. Potential therapeutic approaches for IgAN with HT/pre-HT might be directed toward the management of coagulation status, active lesions, and hemodynamics for slowing disease progression.


Assuntos
Glomerulonefrite por IGA/epidemiologia , Hipertensão/epidemiologia , Pré-Hipertensão/epidemiologia , Adolescente , Fatores Etários , Anti-Hipertensivos/uso terapêutico , Biomarcadores , Criança , Creatinina/sangue , Progressão da Doença , Feminino , Fibrinolíticos/uso terapêutico , Taxa de Filtração Glomerular , Glomerulonefrite por IGA/tratamento farmacológico , Glomerulosclerose Segmentar e Focal/epidemiologia , Humanos , Hipertensão/tratamento farmacológico , Imunossupressores/uso terapêutico , Masculino , Pré-Hipertensão/tratamento farmacológico , Prognóstico , Tempo de Protrombina , Estudos Retrospectivos , Fatores de Risco
6.
Acta Pharmacol Sin ; 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-33087838

RESUMO

Aberrant activation of the RAS superfamily is one of the critical factors in carcinogenesis. Among them, KRAS is the most frequently mutated one which has inspired extensive studies for developing approaches to intervention. Although the cognition toward KRAS remains far from complete, mounting evidence suggests that a variety of post-translational modifications regulate its activation and localization. In this review, we summarize the regulatory mode of post-translational modifications on KRAS including prenylation, post-prenylation, palmitoylation, ubiquitination, phosphorylation, SUMOylation, acetylation, nitrosylation, etc. We also highlight the recent studies targeting these modifications having exhibited potent anti-tumor activities.

7.
Cancer Biomark ; 29(1): 25-37, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32568175

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is the most common malignant tumor worldwide. This work focuses on investigating the role of circ_0000353 in NSCLC and its potential mechanism of action. METHODS: The expression levels of circ_0000353 and miR-411-5p in NSCLC and their matched normal lung tissues were detected by real-time PCR (RT-PCR). The correlation between the circ_0000353 expression and the clinicopathological parameters of NSCLC patients was also analyzed. CCK-8, BrdU and colony formation assays were adopted to detect the role of circ_0000353 in the proliferation of NSCLC cells. The metastasis of NSCLC cells was measured by Transwell assay. The dual-luciferase reporter gene assay was used to confirm the targeting relationship between circ_0000353 and miR-411-5p. The expression level of FOXO1 was detected by western blot. RESULTS: Circ_0000353 was significantly down-regulated in NSCLC tissues and cell lines, and the decreased expression was significantly linked to the increased clinical stage, larger tumor volume, and metastasis. The circ_0000353 over-expression restrained the proliferation, migration, and invasion of NSCLC cells in vitro. Additionally, up-regulation of miR-411-5p was observed in NSCLC tissues and cell lines, and luciferase assay and RT-PCR assay showed that circ_0000353 over-expression could target miR-411-5p and suppress its expression. Further studies confirmed that circ_0000353 and miR-411-5p modulated the FOXO1 expression. CONCLUSION: Circ_0000353 repressed the proliferation, migration, and invasion of NSCLC cells via inhibition of miR-411-5p and up-regulation of FOXO1.

8.
Chin Med J (Engl) ; 133(13): 1540-1545, 2020 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-32568869

RESUMO

BACKGROUND: About 10% of patients get a surgical-site infection (SSI) after radical gastrectomy for gastric cancer, but SSI remains controversial among surgeons. The aim of this study was to explore the risk factors for SSIs after radical gastrectomy in patients with gastric cancer to guide clinical therapies and reduce the incidence of SSI. METHODS: The study was a retrospective cohort study in patients who underwent radical gastrectomy for gastric cancer. SSI was defined in accordance with the National Nosocomial Infection Surveillance System. We evaluated patient-related and peri-operative variables that could be risk factors for SSIs. The Chi-squared test and logistic regression analysis were used to assess the association between these risk factors and SSI. RESULTS: Among the 590 patients, 386 were men and 204 were women. The mean age was 56.6 (28-82) years and 14.2% (84/590) of these patients had an SSI. Among them, incisional SSI was observed in 23 patients (3.9%) and organ/space SSI in 61 patients (10.3%). Multivariate logistic regression analysis identified sex (odds ratios [ORs] = 2.548, and 95% confidence interval [CI]: 1.268-5.122, P = 0.009), total gastrectomy (OR = 2.327, 95% CI: 1.352-4.004, P = 0.002), albumin level (day 3 after surgery) <30 g/L (OR = 1.868, 95% CI: 1.066-3.274, P = 0.029), and post-operative total parenteral nutrition (OR = 2.318, 95% CI: 1.026-5.237, P = 0.043) as independent risk factors for SSI. CONCLUSIONS: SSI was common among patients after radical gastrectomy for gastric cancer. The method supporting post-operative nutrition and the duration of prophylactic antibiotics may be important modifiable influencing factors for SSI.

9.
Microb Ecol ; 2020 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-32588072

RESUMO

Fusarium wilt of tomato caused by the pathogen Fusarium oxysporum f. sp. lycopersici (Fol) is one of the most devastating soilborne diseases of tomato. To evaluate whether microbial community composition associated with Fol-infected tomato is different from healthy tomato, we analyzed the tomato-associated microbes in both healthy and Fol-infected tomato plants at both the taxonomic and functional levels; both bacterial and fungal communities have been characterized from bulk soil, rhizosphere, rhizoplane, and endosphere of tomatoes using metabarcoding and metagenomics approaches. The microbial community (bacteria and fungi) composition of healthy tomato was significantly different from that of diseased tomato, despite similar soil physicochemical characteristics. Both fungal and bacterial diversities were significantly higher in the tomato plants that remained healthy than in those that became diseased; microbial diversities were also negatively correlated with the concentration of Fol pathogen. Network analysis revealed the microbial community of healthy tomato formed a larger and more complex network than that of diseased tomato, probably providing a more stable community beneficial to plant health. Our findings also suggested that healthy tomato contained significantly greater microbial consortia, including some well-known biocontrol agents (BCAs), and enriched more functional genes than diseased tomato. The microbial taxa enriched in healthy tomato plants are recognized as potential suppressors of Fol pathogen invasion.

10.
ACS Appl Mater Interfaces ; 12(17): 19840-19854, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32270675

RESUMO

Multifunctional lanthanide-doped upconversion nanoparticles (UCNPs) have spread their wings in the fields of flexible optoelectronics and biomedical applications. One of the ongoing challenges lies in achieving UCNP-based nanocomposites, which enable a continuous-wave (CW) laser action at ultralow thresholds. Here, gold sandwich UCNP nanocomposites [gold (Au1)-UCNP-gold (Au2)] capable of exhibiting lasing at ultralow thresholds under CW excitation are demonstrated. The metastable energy-level characteristics of lanthanides are advantageous for creating population inversion. In particular, localized surface plasmon resonance-based electromagnetic hotspots in the nanocomposites and the huge enhancement of scattering coefficient for the formation of coherent closed loops due to multiple scattering facilitate the process of stimulated emissions as confirmed by theoretical simulations. The nanocomposites are subjected to stretchable systems for enhancing the lasing action (threshold ∼ 0.06 kW cm-2) via a light-trapping effect. The applications in bioimaging of HeLa cells and antibacterial activity (photothermal therapy) are demonstrated using the newly designed Au1-UCNP-Au2 nanocomposites.

11.
Risk Manag Healthc Policy ; 13: 303-311, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32308513

RESUMO

Purpose: Currently, thalassemia is commonly detected using gap-polymerase chain reaction (PCR) and deoxyribonucleic acid (DNA) reverse dot blot, which have high requirements of space, instruments, and personnel. Therefore, it is necessary to develop a new method for thalassemia detection with high sensitivity, low cost, and simple and fast operation. In this study, we aimed to design and evaluate a new method for detecting three α-thalassemia genes including -Southeast Asian (SEA), -α3.7, and -α4.2 and five ß-thalassemia genes including 654M, 41/42M, -28M, 17M, and 27/28M based on loop-mediated isothermal amplification (LAMP). Methods: Primer sequences were designed using Primer Explorer V4 software. Blood samples (5 mL) were collected from all participants in EDTA. DNA was extracted using Chelex 100 and was subjected to LAMP. LAMP products were detected by fluorescence development in ultraviolet light. Results: We found that LAMP assays for positive samples of thalassemia reached a plateau before 60 minutes, whereas the negative control samples entered the plateau after 70 minutes or showed no amplification. The concentration range of positive reactions was between 20-60 pg/µL and 20-60 ng/µL. Additionally, there were no cross-reactivities among 8 thalassemia subtypes. For clinical samples, the positive sample tube showed strong green fluorescence, whereas the negative tube showed light green fluorescence. According to these results, the LAMP method has high sensitivity for detecting thalassemia (252/254). However, 43 false-positive results were obtained in the LAMP test. The LAMP assay was also of low cost and with simple and fast operation. Conclusion: The novel LAMP assay can be completed within 60 min using a heating block or a water bath, and the result can be read visually based on color change to detect thalassemia. The LAMP assay fulfills the requirements of field application and resource-limited areas, especially those with primary hospitals and rural areas.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32328134

RESUMO

Objective: To explore the status of electroacupuncture (EA) among other treatments for peripheral facial paralysis (PFP). Methods: Randomized controlled trials comparing EA with other treatments that met the eligibility criteria published in databases were included. The differences were observed and quantified through the risk ratio (RR) for dichotomous outcomes and the standardized mean difference (SMD) for continuous outcomes. Then, their 95% confidence intervals (CI) were recorded. Results: Twenty-three studies involving 1985 participants were included. META-analysis results showed that EA was better than manual acupuncture for PFP (RR: 1.16, 95% CI 1.11 to 1.22, for responding rate; SMD: 2.26, 95% CI 0.15 to 4.37, for facial nerve function) and current promoted recovery (RR: 1.21, 95% CI 1.15 to 1.27, for responding rate; SMD: 2.87, 95% CI 1.16 to 4.58, for facial nerve function). When combined with other treatments, EA improved their effectiveness (RR: 1.19, 95% CI 1.12 to 1.28, responding rate; SMD: 1.85, 95% CI 0.67 to 3.03, facial nerve function). Conclusion: Patients with PFP received EA (used separately or combined with other treatments) resulting in a better prognosis. However, the quality of evidence was very low-to-moderate. Considering the poor quality of evidence, we are not very confident in the results. We look forward to more research and update results in the future and improve the evidence quality.

13.
Cancers (Basel) ; 12(3)2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32168902

RESUMO

Hepatitis B virus (HBV) is one of predisposing factors for hepatocellular carcinoma (HCC). The role of HBV x protein (HBx) in mediating the induction and maintenance of cancer stemness during HBV-related HCC attracts considerable attention, but the exact mechanism has not been clearly elucidated. Here, ABCG2-dependent stem-like side population cells, which are thought to be liver cancer stem cells (LCSCs), were present in HCC cells, and the fraction of this subset was increased in HBx-expressing HCC cells. In addition, glycolysis was upregulated in LCSCs and HBx-expressing HCC cells, and intervention of glycolysis attenuated cancer stem-like phenotypes. Mitochondria play an important role in the maintenance of energy homeostasis, BNIP3L-dependent mitophagy was also activated in LCSCs and HBx-expressing HCC cells, which triggered a metabolic shift toward glycolysis. In summary, we proposed a positive feedback loop, in which HBx induced BNIP3L-dependent mitophagy which upregulated glycolytic metabolism, increasing cancer stemness of HCC cells in vivo and in vitro. BNIP3L might be a potential therapeutic target for intervention of LCSCs-associated HCC. Anti-HBx, a monoclonal antibody targeting intracellular HBx, had the potential to delay the progression of HBV infection related-HCC.

14.
Nanoscale ; 12(13): 7188-7195, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32195509

RESUMO

Exploring ultrathin two-dimensional (2D) solid electrolytes with fast ion transport is highly desirable in nanoelectronics, ionic devices and various energy storage systems, following the rapid scaling of devices to the nanometer scale. Herein, two-dimensional (2D) metal trihalides MX3 (ScCl3, ScBr3, AsI3, ScI3, YBr3, SbI3, YI3 and BiI3) with intrinsic atomic pore structures have been examined and found to be promising as realistic 2D solid electrolytes. Through examining the binding interactions and the diffusion barriers of monolayer MX3-ion (Li+, Na+, K+, Mg2+, and Ca2+) systems by utilizing first principles calculations, it is found that MX3-ion complexes are energetically favorable and the energy barriers of some MX3-ion systems are comparable to or even smaller than those of the conventional solid electrolyte systems. More significantly, the short diffusion time of Na+ and K+ ions in some monolayers MX3 at the nanosecond (ns) or even at the sub-ns scale indicates fast ion transport. In terms of practical applications, ultrafast Li+ travelling in the timescale of sub-ns to ns and Na+ in several tens ns in few-layer MX3 is achieved. In addition, the insulating nature of wide band gaps for MX3 is maintained during the ion transport, which is essential for solid electrolytes. These theoretical results provide fundamental guidance that MX3 materials with natural atomic pores are realistic candidates for 2D solid electrolytes with broad applications in ionic devices and energy storage devices.

15.
Nat Commun ; 11(1): 314, 2020 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-31949139

RESUMO

Metallic glasses are expected to have quite tunable structures in their configuration space, without the strict constraints of a well-defined crystalline symmetry and large energy barriers separating different states in crystals. However, effectively modulating the structure of metallic glasses is rather difficult. Here, using complementary in situ synchrotron x-ray techniques, we reveal thermal-driven structural ordering in a Ce65Al10Co25 metallic glass, and a reverse disordering process via a pressure-induced rejuvenation between two states with distinct structural order characteristics. Studies on other metallic glass samples with different compositions also show similar phenomena. Our findings demonstrate the feasibility of two-way structural tuning states in terms of their dramatic ordering and disordering far beyond the nearest-neighbor shells with the combination of temperature and pressure, extending accessible states of metallic glasses to unexplored configuration spaces.

16.
Adv Mater ; 32(4): e1906384, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31808585

RESUMO

Although various catalytic materials have emerged for hydrogen evolution reaction (HER), it remains crucial to develop intrinsically effective catalysts with minimum uses of expensive and scarce precious metals. Metallic glasses (MGs) or amorphous alloys show up as attractive HER catalysts, but have so far limited to material forms and compositions that result in high precious-metal loadings. Here, an Ir25 Ni33 Ta42 MG nanofilm exhibiting high intrinsic activity and superior stability at an ultralow Ir loading of 8.14 µg cm-2 for HER in 0.5 m H2 SO4 is reported. With an overpotential of 99 mV for a current density of 10 mA cm-2 , a small Tafel slope of 35 mV dec-1 , and high turnover frequencies of 1.76 and 19.3 H2 s-1 at 50 and 100 mV overpotentials, the glassy film is among the most intrinsically active HER catalysts, outcompetes any reported MG, representative sulfides, and phosphides, and compares favorably with other precious-metal-containing catalysts. The outstanding HER performance of the Ir25 Ni33 Ta42 MG film is attributed to the synergistic effect of the novel alloy system and amorphous structure, which may inspire the development of multicomponent alloys for heterogeneous catalysis.

17.
Artigo em Inglês | MEDLINE | ID: mdl-31781517

RESUMO

Background: Sexually transmitted diseases (STD) are a major cause of infertility, long-term disability, ectopic pregnancy, and premature birth. Therefore, the development of fast and low-cost laboratory STD diagnostic screening methods will contribute to reducing STD-induced reproductive tract damage and improve women's health worldwide. In this study, we evaluated a novel multiplex real-time PCR melting curve assay method for the simultaneous detection of 9 STD pathogens, including Chlamydia trachomatis, Neisseria gonorrhoeae, Mycoplasma genitalium, Trichomonas vaginalis, Mycoplasma hominis, Ureaplasma urealyticum, Ureaplasma parvum, and herpes simplex virus. Methods: The analytical performance of the method, including its limit of detection (LOD), specificity, repeatability, and effect on different DNA extraction kits were evaluated. Additionally, we obtained 1,328 clinical specimens from 3 hospitals to detect the 9 STD pathogens using multiplex real-time PCR melting curve and Sanger sequencing, to evaluate the sensitivity, specificity, and consistency of the assay method. Results: The results showed that the analytical sensitivity of the novel multiplex real-time PCR melting curve assay is very excellent, with LOD of DNA corresponding to <200 copies/µL for the DNA of the 9 STDs and 1.00 × 104 color change unit /ml for those of UU and UP. Additionally, this assay demonstrated excellent analytical specificity, excellent repeatability, and its results had no effect of different DNA extraction kits. The performance, in terms of sensitivity (91.06-100%) and specificity (99.14-100%), was remarkable, since the consistency between it and Sanger sequencing was more than 0.85 in the clinic. Conclusion: The novel multiplex real-time PCR melting curve assay method has high sensitivity and specificity, relatively low cost, and simple to use for the simultaneous detection of 9 STD pathogens in genitourinary secretions.


Assuntos
Secreções Corporais , Reação em Cadeia da Polimerase em Tempo Real , Doenças Sexualmente Transmissíveis/diagnóstico , Doenças Sexualmente Transmissíveis/etiologia , Sistema Urogenital/metabolismo , Feminino , Humanos , Masculino , Reação em Cadeia da Polimerase Multiplex/métodos , Reação em Cadeia da Polimerase Multiplex/normas , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase em Tempo Real/normas , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
18.
J Neurosci ; 39(46): 9107-9118, 2019 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-31597725

RESUMO

Although several genes have been identified to promote axon regeneration in the CNS, our understanding of the molecular mechanisms by which mammalian axon regeneration is regulated is still limited and fragmented. Here by using female mouse sensory axon and optic nerve regeneration as model systems, we reveal an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. We also provide evidence that TERT and p53 act downstream of c-Myc to control sensory axon regeneration. More importantly, overexpression of p53 in sensory neurons and retinal ganglion cells is sufficient to promote sensory axon and optic never regeneration, respectively. The study reveals a novel c-Myc-TERT-p53 signaling pathway, expanding horizons for novel approaches promoting CNS axon regeneration.SIGNIFICANCE STATEMENT Despite significant progress during the past decade, our understanding of the molecular mechanisms by which mammalian CNS axon regeneration is regulated is still fragmented. By using sensory axon and optic nerve regeneration as model systems, the study revealed an unexpected role of telomerase reverse transcriptase (TERT) in regulation of axon regeneration. The results also delineated a c-Myc-TERT-p53 pathway in controlling axon growth. Last, our results demonstrated that p53 alone was sufficient to promote sensory axon and optic nerve regeneration in vivo Collectively, the study not only revealed a new mechanisms underlying mammalian axon regeneration, but also expanded the pool of potential targets that can be manipulated to enhance CNS axon regeneration.


Assuntos
Axônios/metabolismo , Gânglios Espinais/metabolismo , Regeneração Nervosa , Nervo Óptico/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Telomerase/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Células Cultivadas , Feminino , Camundongos Endogâmicos C57BL
19.
Nano Lett ; 19(12): 8911-8919, 2019 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-31661286

RESUMO

A molecularly thin electrolyte is developed to demonstrate a nonvolatile, solid-state, one-transistor (1T) memory based on an electric-double-layer (EDL) gated WSe2 field-effect transistor (FET). The custom-designed monolayer electrolyte consists of cobalt crown ether phthalocyanine and lithium ions, which are positioned by field-effect at either the surface of the WSe2 channel or an h-BN capping layer to achieve "1" or "0", respectively. Bistability in the monolayer electrolyte memory is significantly improved by the h-BN cap with density functional theory (DFT) calculations showing enhanced trapping of Li+ near h-BN due to a ∼1.34 eV increase in the absolute value of the adsorption energy compared to vacuum. The threshold voltage shift between the two states corresponds to a change in charge density of ∼2.5 × 1012 cm-2, and an On/Off ratio exceeding 104 at a back gate voltage of 0 V. The On/Off ratio remains stable after 1000 cycles and the retention time for each state exceeds 6 h (max measured). When the write time approaches 1 ms, the On/Off ratio remains >102, showing that the monolayer electrolyte-gated FET can respond on time scales similar to existing flash memory. The data suggest that faster switching times and lower switching voltages could be feasible by top gating.

20.
Arch Toxicol ; 93(11): 3305-3320, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31612242

RESUMO

Aflatoxin B1 (AFB1), a food contaminant derived from Aspergillus fungi, has been reported to cause hepatic immunotoxicity via inflammatory infiltration and cytokines release. As a pro-inflammatory factor, cyclooxygenase-2 (COX-2) is widely involved in liver inflammation induced by xenobiotics. However, the mechanism by which AFB1-induced COX-2 regulates liver inflammatory injury via hepatocytes-Kupffer cells (KCs) crosstalk remains unclear and requires further elucidation. Here, we established a COX-2 upregulated model with AFB1 treatment in vivo (C57BL/6 mice, 1 mg/kg body weight, i.g, 4 weeks) and in vitro (human liver HepaRG cells, 1 µM for 24 h). In vivo, AFB1-treated mice exhibited NLRP3 inflammasome activation, inflammatory infiltration, and increased recruitment of KCs. In vitro, dephosphorylated COX-2 by protein phosphatase 2A (PP2A)-B55δ promoted NLRP3 inflammasome activation, including mitochondrial translocation of NLRP3, caspase 1 cleavage, and IL-1ß release. Moreover, phosphorylated COX-2 at serine 601 (p-COX-2Ser601) underwent endoplasmic reticulum (ER) retention for proteasome degradation. Furthermore, pyroptosis and inflammatory response induced by AFB1 were relieved with COX-2 genetic (siPTGS2) intervention or pharmaceutic (celecoxib, 30 mg/kg body weight, i.g, 4 weeks) inhibition of COX-2 via NLRP3 inflammasome suppression in vivo and in vitro. Ex vivo, in a co-culture system with murine primary hepatocytes and KCs, activated KCs induced by damaged signals from pyroptotic hepatocytes, formed a feedback loop to amplify NLRP3-dependent pyroptosis of hepatocytes via pro-inflammatory signaling, leading to liver inflammatory injury. Taken together, our data suggest a novel mechanism that protein quality control of COX-2 determines the intracellular distribution and activation of NLRP3 inflammasome, which promotes liver inflammatory injury via hepatocytes-KCs crosstalk.


Assuntos
Aflatoxina B1/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Ciclo-Oxigenase 2/metabolismo , Hepatócitos/efeitos dos fármacos , Macrófagos do Fígado/efeitos dos fármacos , Piroptose/efeitos dos fármacos , Animais , Linhagem Celular Tumoral , Doença Hepática Induzida por Substâncias e Drogas/imunologia , Doença Hepática Induzida por Substâncias e Drogas/patologia , Células HEK293 , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Inflamação , Interleucina-1beta/metabolismo , Macrófagos do Fígado/metabolismo , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Camundongos Endogâmicos C57BL , Fosforilação , Cultura Primária de Células
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