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1.
ACS Nano ; 2020 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-32052962

RESUMO

Nanoscale laser sources with downscaled device footprint, high energy efficiency, and high operation speed are pivotal for a wide array of optoelectronic and nanophotonic applications ranging from on-chip interconnects, nanospectroscopy, and sensing to optical communication. The capability of on-demand lasing output with reversible and continuous wavelength tunability over a broad spectral range enables key functionalities in wavelength-division multiplexing and finely controlled light-matter interaction, which remains an important subject under intense research. In this study, we demonstrate an electrically controlled wavelength-tunable laser based on a CdS nanoribbon (NR) structure. Typical "S"-shaped characteristics of pump power dependence were observed for dominant lasing lines, with concomitant line width narrowing. By applying an increased bias voltage across the NR device, the lasing resonance exhibits a continuous tuning from 510 to 520 nm for a bias field in the range 0-15.4 kV/cm. Systematic bias-dependent absorption and time-resolved photoluminescence (PL) measurements were performed, revealing a red-shifted band edge of gain medium and prolonged PL lifetime with increased electric field over the device. Both current-induced thermal reduction of the band gap and the Franz-Keldysh effect were identified to account for the modification of the lasing profile, with the former factor playing the leading role. Furthermore, dynamical switching of NR lasing was successfully demonstrated, yielding a modulation ratio up to ∼21 dB. The electrically tuned wavelength-reversible CdS NR laser in this work, therefore, presents an important step toward color-selective coherent emitters for future chip-based nanophotonic and optoelectronic circuitry.

2.
Bioorg Chem ; 95: 103545, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31927316

RESUMO

A phytochemical study on the roots of Daphne genkwa yielded seven new guaiane-type sesquiterpenoids (1-7), daphne A-G. Their structures were elucidated through comprehensive spectroscopic analyses. The absolute configurations were determined by comparison between experimental electronic circular dichroism (ECD) and calculated ECD spectra via time-dependent density functional theory (TDDFT) and the modified Mosher's method. Furthermore, all isolates were evaluated for their neuroprotective activities against H2O2-induced injury in human neuroblastoma SH-SY5Y cells. Among them, compounds 1 (78.42%) and 4 (79.34%) exhibited potent neuroprotective effects against H2O2-induced neurotoxicity at 25 µM. Further Annexin V-FITC/propidium iodide (PI) doubling staining exhibited that the neuroprotective effects of compounds 1 and 4 appeared to be mediated via suppressing cell apoptosis. Flow cytometry assays also proved that compounds 1 and 4 could attenuate mitochondrial dysfunction in SH-SY5Y cells.

3.
Coron Artery Dis ; 31(2): 109-117, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31464730

RESUMO

BACKGROUND: This study investigated whether the age, creatinine, and ejection fraction (ACEF) score [age (years) /ejection fraction (%) +1 (if creatinine>176µmol/L)] could predict 1-year outcomes following ST-segment elevation myocardial infarction after percutaneous coronary intervention, and whether accuracy could be improved by establishing novel ACEF-derived risk models. METHODS: A total of 1146 patients were included. The study endpoint was 1-year major adverse cardio-cerebrovascular events, including all-cause death, nonfatal myocardial infarction, unplanned revascularization, and nonfatal stroke. Accuracy was defined with area under the curve by receiver-operating characteristic curve analysis. RESULTS: The incidence of 1-year major adverse cardio-cerebrovascular event increased with the rising age, creatinine, and ejection fraction score tertiles (4.8%, 8.4%, and 15.2%, P < 0.001 for all). Higher ACEF score was significantly associated with an increased risk of the endpoint in overall (odds ratio = 3.75, 95% confidence interval, 2.44-5.77, P < 0.001) and in subgroups (all P < 0.05). The accuracy of the ACEF score was equivalent to the other complex risk scores. The combination of ACEF, and diabetes (ACEF-diabetes score) yielded a superior discriminatory ability than the original ACEF score (increase in C-statistic from 0.67 to 0.71, P = 0.048; continuous net reclassification improvement = 51.9%, 95% confidence interval, 33.4-70.5%, P < 0.001; integrated discrimination improvement = 0.020, 95% confidence interval, 0.011-0.030, P < 0.001). CONCLUSIONS: The simplified ACEF score performed well in predicting 1-year outcomes in ST-segment elevation myocardial infarction patients undergoing percutaneous coronary intervention. The novel ACEF-diabetes score provided a better predictive value and thus may help stratify high-risk patients and potentially facilitate decision making.

4.
Forensic Sci Int Genet ; 44: 102167, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31605960

RESUMO

BACKGROUND: Monozygotic (MZ) twins, considered genetically identical, cannot be distinguished using regular short tandem repeats (STR) typing, thus presenting a challenge for forensic geneticists. In paternity testing, single nucleotide polymorphisms (SNPs) in nuclear DNA can help distinguish MZ twins. However, the unique features of the mitochondrial genome, such as high copy number, small genome size, and high substitution rate, make it a promising source for applications in forensic science. METHODS: Whole-genome sequencing (WGS) was performed on blood samples, and bioinformatic analysis was used to distinguish between MZ twins. Amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used to confirm the WGS results. This methodology was further applied to forensic samples from criminal cases. Amplicon sequencing was also performed to further exclude the innocent twin. RESULTS: The monozygosity of the twins was confirmed using STR typing. Only one potential somatic mutation, m.6903 T > C (2.6%), in the mitochondrial genome of one of the twins was verified when the sequence depth was set to 2000-fold, while no other distinguishing locus in the nuclear genome was identified. By dividing the number of C-reads by total reads, WGS data confirmed the amount of the minor component C to be 2.6%, which was further confirmed by ARMS-PCR. In addition, the heterogeneous locus was used to identify samples obtained from four criminal cases for forensic testing. Two heterogeneous loci in the sperm DNA of the other twin were identified by amplicon sequencing, and the amount of minor component T in m.6935C > T and m.6938C > T was estimated to be 17.91% and 18.79%, respectively. CONCLUSION: The biological samples taken from the MZ twins were distinguished using a combination of WGS, allele-specific PCR, and deep-amplicon sequencing. Compared with nuclear DNA, mitochondrial DNA exhibited a higher potential for distinguishing between the MZ twins. The distinguishing feature of the mitochondrial DNA was the heterogeneous SNPs that occurred in only one twin. One SNP was further verified in the samples from the criminal cases and helped identify the perpetrator in case 1 and case 2. Furthermore, two heterogeneous SNPs found by amplicon sequencing helped to exclude the innocent twin in all four cases. Our findings demonstrated that a combination of deep sequencing and molecular analysis can be an effective way to distinguish between identical twins and can be used to analyze samples from criminal cases.

5.
Angiology ; 71(1): 38-47, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31554413

RESUMO

This study investigated whether a novel index of stress hyperglycemia might have a better prognostic value compared to admission glycemia alone in patients with ST-segment elevation myocardial infarction (STEMI) undergoing percutaneous coronary intervention (PCI). The acute-to-chronic glycemic ratio was expressed as admission blood glucose (ABG) devided by the estimated average glucose (eAG), and eAG was derived from the glycated hemoglobin (HbA1c). A total of 1300 consecutive patients with STEMI treated with PCI were included. Baseline data and outcomes were analyzed. The study end point was a composite of in-hospital all-cause death, cardiogenic shock, and acute pulmonary edema. Accuracy was defined with area under the curve (AUC) by a receiver-operating characteristic (ROC) curve analysis. After multivariate adjustment, both ABG/eAG and ABG were closely associated with an increased risk of the composite end point in nondiabetic patients. However, only ABG/eAG (odds ratio = 2.45, 95% confidence interval: 1.24-4.82, P = .010), instead of ABG, was associated with the outcomes in diabetic patients. Compared to ABG, ABG/eAG had an equivalent predictive value in nondiabetic patients but a superior discriminatory ability in diabetic patients (AUC improved from 0.52-0.63, P < .001). Taken together, ABG/eAG provides more significant in-hospital prognostic information than ABG in diabetic patients with STEMI after PCI.


Assuntos
Glicemia/metabolismo , Hemoglobina A Glicada/metabolismo , Admissão do Paciente , Intervenção Coronária Percutânea , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Idoso , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intervenção Coronária Percutânea/efeitos adversos , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Fatores de Tempo , Resultado do Tratamento
6.
Cancer Cell Int ; 19: 290, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754347

RESUMO

Background: Hepatocellular carcinoma (HCC) is a serious threat to public health due to its poor prognosis. The current study aimed to develop and validate a prognostic nomogram to predict the overall survival of HCC patients. Methods: The model cohort consisted of 24,991 mRNA expression data points from 348 HCC patients. The least absolute shrinkage and selection operator method (LASSO) Cox regression model was used to evaluate the prognostic mRNA biomarkers for the overall survival of HCC patients. Results: Using multivariate Cox proportional regression analyses, a prognostic nomogram (named Eight-mRNA prognostic nomogram) was constructed based on the expression data of N4BP3, -ADRA2B, E2F8, MAPT, PZP, HOXD9, COL15A1, and -NDST3. The C-index of the Eight-mRNA prognostic nomogram was 0.765 (95% CI 0.724-0.806) for the overall survival in the model cohort. The Harrell's concordance-index of the Eight-mRNA prognostic nomogram was 0.715 (95% CI 0.658-0.772) in the validation cohort. The survival curves demonstrated that the HCC patients in the high risk group had a significantly poorer overall survival than the patients in the low risk group. Conclusion: In the current study, we have developed two convenient and efficient predictive precision medicine tools for hepatocellular carcinoma. These two predictive precision medicine tools are helpful for predicting the individual mortality risk probability and improving the personalized comprehensive treatments for HCC patients. The Smart Cancer Predictive System can be used by clicking the following URL: https://zhangzhiqiao2.shinyapps.io/Smart_cancer_predictive_system_HCC_2/. The Gene Survival Analysis Screen System is available at the following URL: https://zhangzhiqiao5.shinyapps.io/Gene_Survival_Analysis_A1001/.

7.
Biomed Pharmacother ; 120: 109527, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31629953

RESUMO

Excessive formation of advanced glycation end products (AGEs) impairs voltage-gated potassium (Kv) channels in rat coronary artery smooth muscle cells (CSMCs), resulting in weakened Kv-mediated coronary vasodilation. We hypothesized that induction of the nuclear factor-κB (NF-κB) signaling pathway by AGEs plays a significant role in the regulation of Kv channel-mediated vasodilation in Zucker diabetic fatty (ZDF) rats. Assays of mRNA transcripts, protein expression, and intracellular localization as well as patch-clamp experiments in cultured CSMCs revealed that AGEs significantly induced activation of the NF-κB signaling pathway, reduced Kv1.2/1.5 expression, and inhibited Kv currents. In addition, silencing of the receptor for AGEs (RAGE) or p65 with siRNA and treatment with alagrebrium (ALA) or pyrrolidine dithiocarbamate (PDTC) alleviated the AGE-induced impairment of Kv channels in CSMCs. Compared with Zucker lean (ZL) rats, the amount of AGEs, RAGE protein expression, and NF-κB activity in coronary arteries were higher in ZDF rats; whereas Kv1.2/1.5 expression was significantly lower in ZDF rats. Reduced Kv1.2/1.5 expression in coronary arteries and impaired Kv-mediated coronary relaxation tested by wire myography in ZDF rats were markedly improved by treatment with aminoguanidine (AG), ALA, or PDTC. These effects were accompanied by diminished NF-κB activity, inflammation, and oxidative stress. Taken together, these results indicate that an increased interaction between AGEs and RAGE in diabetic rats leads to impaired Kv channel-mediated coronary vasodilation. Moreover, activation of the NF-κB signaling pathway and a subsequent increase of inflammation and oxidative stress may play an important role in AGE-induced impairment of coronary vasodilation in diabetes.

8.
J Chem Inf Model ; 59(10): 4393-4401, 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31585031

RESUMO

Cypridina bioluminescence has been increasingly used in bioimaging, bioanalysis, and biomedicine, due to high quantum yield and high signal-to-noise ratio. However, there is still no consensus regarding different aspects of the chemiluminescent mechanism of this system, which impairs the development of new applications. Herein, we have used a theoretical DFT and TD-DFT approach to (i) determine the identity of the dioxetanone species responsible for efficient chemiexcitation and (ii) identify the bioluminescent emitter and determine if light-emission occurs from the fluorescent or chemiluminescent state. Our results demonstrate that upon oxygenation of the imidazopyrazinone scaffold, a dioxetanone with a neutral amide group and a cationic guanidinopropyl group is formed. This species is efficiently chemiexcited (with no obvious charge transfer step) to the corresponding oxyluciferin with a neutral amide and cationic guanidinopropyl groups. After the "dark" chemiluminescent state, this oxyluciferin species is converted into a bright blue-emitting fluorescent state.

9.
Biomed Pharmacother ; 118: 109346, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31506251

RESUMO

AIMS: Renal interstitial fibrosis and glomerulosclerosis are the characteristic presentation of diabetic nephropathy progression. Twist-1 overexpression contributes to renal fibrosis. Previous studies have demonstrated that pioglitazone (PIO), a PPAR-γ agonists, can ameliorate renal fibrosis and protect renal function. However, whether PIO attenuates renal fibrosis and delays diabetic nephropathy progression by regulating Twist-1 expression remains unclear. METHODS: Male Zucker diabetic fatty (ZDF) rats were randomly divided into 3 groups: (1) ZDF group, (2) ZDF + PIO group treated with PIO for 10 weeks, (3) ZDF + PIO + GW9662 group treated with GW9662 (a PPAR-γ antagonist) and PIO for 10 weeks. Age-matched Zucker lean rats (ZL group) were used as a control group. Urinary albumin/creatinine ratio (UACR) and renal blood flow were measured. Renal histopathology and Twist-1 expression were determined by immunohistochemistry. The protein and mRNA levels of Twist-1 and PPAR-γ were analyzed by Western blot and qRT-PCR. RESULTS: PIO considerably reduced UACR and improved renal blood flow. This was associated with amelioration of glomerulosclerosis and tubulointerstitial fibrosis evidenced by the expression decrease of collagen I, aquaporin 1, α-SMA, transforming growth factor ß1 and nephrin, although glycaemia remained high. Moreover, Twist-1 protein and mRNA expression in kidney of ZDF rats were significantly increased compared with ZL rats and PIO significantly decreased Twist-1 levels. CONCLUSIONS: This study shows that PIO can downregulate Twist-1 expression in the kidney, inhibit renal fibrosis and protect renal function in ZDF rats. These PIO-mediated effects are independent of glycemic control.

10.
Sensors (Basel) ; 19(19)2019 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-31561609

RESUMO

A heatsink is a large experimental device which is used to simulate the outer space environment. In this paper, a Raman-based distributed temperature sensor was used for real-time and continuous heatsink temperature monitoring, and a special Raman-based distributed temperature sensing method and system have been proposed. This method takes advantage of three calibration parameters ( Δ α , γ , C ) to calculate the temperature. These three parameters are related to the attenuation of the optical fiber, the Raman translation, and the difference of optoelectronic conversion, respectively. Optical time domain reflectometry was used to calculate the location. A series of heatsink temperature measurement experiments were performed in a vacuum and -173 °C environment. When the temperature dropped to -100 °C, the parameter Δ α was found to vary. A method was proposed to recalculate Δ α and modify the traditional Raman fiber temperature equation. The results of the experiments confirmed the validity of this modified Raman fiber temperature equation. Based on this modified equation, the temperature field in the heatsink was calculated. The Raman-based distributed temperature sensor has potential applications in temperature measurement and judging the occurrence of faults in space exploration.

11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(8): 794-797, 2019 Aug 10.
Artigo em Chinês | MEDLINE | ID: mdl-31400130

RESUMO

OBJECTIVE: To explore the molecular basis for a pedigree affected with Darier-White disease. METHODS: Genomic DNA was isolated from 3 patients and 1 unaffected member from the pedigree, as well as 80 healthy controls. Targeted sequence capture and next-generation sequencing were used to screen mutations of skin disease-related genes. Candidate mutations were verified by Sanger sequencing, and co-segregation analysis was carried out to confirm the pathogenicity of mutation. Conservation analysis and protein structure and function were also predicted with Bioinformatic tools. RESULTS: A heterozygous mutation c.2246G>T (p.G749V) was identified in exon 15 of ATP2A2 gene in all 3 patients from the pedigree, but not in the unaffected member or 80 healthy controls. The corresponding amino acid was highly conserved, and mutation of which can lead to structural and functional changes of the protein. CONCLUSION: The c.2246G>T missense mutation of the ATP2A2 gene probably underlies the Darier-White disease in this pedigree by causing damages to the structure and function of sarcoplasmic/endoplasmic reticulum calcium ATPase 2 (SERCA2).


Assuntos
Doença de Darier/genética , ATPases Transportadoras de Cálcio do Retículo Sarcoplasmático/genética , Heterozigoto , Humanos , Mutação de Sentido Incorreto , Linhagem
12.
J Med Chem ; 62(15): 6958-6971, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31343875

RESUMO

Currently, due to the HIV latency mechanism, the search continues for effective drugs to combat this issue and provide a cure for AIDS. Gnidimacrin activates latent HIV-1 replication and inhibits HIV-1 infection at picomolar concentrations. This natural diterpene was able to markedly reduce the latent HIV-1 DNA level and the frequency of latently infected cells. Therefore, gnidimacrin is an excellent lead compound, and its anti-HIV potential merits further investigation. Twenty-nine modified gnidimacrin derivatives were synthesized and evaluated in assays for HIV replication and latency activation to establish which molecular structures must be maintained and which can tolerate changes that may be needed for better pharmacological properties. The results indicated that hydroxyl substituents at C-5 and C-20 are essential, while derivatives modified at 3-OH with aromatic esters retain anti-HIV replication and latent activation activities. The half-lives of the potent GM derivatives are over 20 h, which implies that they are stable in the plasm even though they contain ester linkages. The established structure-activity relationship should be useful in the development of gnidimacrin or structurally related compounds as clinical trial candidates.

13.
Cancer Sci ; 110(9): 2905-2923, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31335995

RESUMO

The aim of the present study is to construct a competitive endogenous RNA (ceRNA) regulatory network by using differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with hepatocellular carcinoma (HCC), and to construct a prognostic model for predicting overall survival (OS) of HCC patients. Differentially expressed lncRNAs, miRNAs, and mRNAs were explored between HCC tissues and normal liver tissues. A prognostic model was built for predicting OS of HCC patients and receiver operating characteristic curves were used to evaluate the performance of the prognostic model. There were 455 differentially expressed lncRNAs, 181 differentially expressed miRNAs, and 5035 differentially expressed mRNAs. A ceRNA regulatory network was constructed based on 43 lncRNAs, 37 miRNAs, and 105 mRNAs. Eight mRNA biomarkers (H2AFX, SQSTM1, ITM2A, PFKP, TPD52L1, ACSL4, STRN3, and CPEB3) were identified as independent risk factors by multivariate Cox regression and were used to develop a prognostic model for OS. The C-indexes in the model group were 0.776 (95% confidence interval [CI], 0.730-0.822), 0.745 (95% CI, 0.699-0.791), and 0.789 (95% CI, 0.743-0.835) for 1-, 3-, and 5-year OS, respectively. The current study revealed potential molecular biological regulation pathways and prognostic biomarkers by the ceRNA regulatory network. A prognostic model based on prognostic mRNAs in the ceRNA network might be helpful to predict the individual mortality risk for HCC patients. The individual mortality risk calculator can be used by visiting the following URL: https://zhangzhiqiao.shinyapps.io/Smart_cancer_predictive_system_HCC/.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , RNA Mensageiro/metabolismo , Adulto , Idoso , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/mortalidade , Conjuntos de Dados como Assunto , Feminino , Seguimentos , Perfilação da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Nomogramas , Prognóstico , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética
14.
Cancer Cell Int ; 19: 174, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312112

RESUMO

Background: Accumulated evidences have demonstrated that long non-coding RNAs (lncRNAs) are correlated with prognosis of patients with hepatocellular carcinoma. The current study aimed to develop and validate a prognostic lncRNA signature to improve the prediction of overall survival in hepatocellular carcinoma patients. Methods: The study cohort involved 348 hepatocellular carcinoma patients with lncRNA expression information and overall survival information. Through gene mining approach, the current study established a prognostic lncRNA signature (named LncRNA risk prediction score) for predicting the overall survival of hepatocellular carcinoma patients. Results: The current study built a predictive nomogram based on ten prognostic lncRNA predictors through Cox regression analysis. In model group, the Harrell's concordance indexes of LncRNA risk prediction score were 0.811 (95% CI 0.769-0.853) for 1-year overall survival, 0.814 (95% CI 0.772-0.856) for 3-year overall survival and 0.796 (95% CI 0.754-0.838) for 5-year overall survival respectively. In validation cohort, the Harrell's concordance indexes of LncRNA risk prediction score were 0.779 (95% CI 0.737-0.821), 0.828 (95% CI 0.786-0.870) and 0.796 (95%CI 0.754-0.838) for 1-year survival, 3-year survival and 5-year survival respectively. LncRNA risk prediction score could stratify hepatocellular carcinoma patients into low risk group and high risk group. Further survival curve analysis demonstrated that the overall survival rate of high risk patients was significantly poorer than that of low risk patients (P < 0.001). Conclusions: In conclusion, the current study developed and validated a prognostic signature to predict the individual mortality risk for hepatocellular carcinoma patients. LncRNA risk prediction score is helpful to identify the patients with high mortality risk and optimize the individualized treatment decision. The web calculator can be used by click the following URL: https://zhangzhiqiao2.shinyapps.io/Smart_cancer_predictive_system_HCC_3/.

15.
J Phys Chem Lett ; 10(14): 4045-4050, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31271533

RESUMO

The phononic topological Weyl closed nodal lines, including Weyl nodal rings, nodal chains, nodal nets, nodal links, and nodal knots, have been widely studied. The phononic topological Weyl open nodal lines (PTWONLs), however, have not been well investigated so far. By analyzing the coexistence of parity inversion and time-reversal symmetries, we found that the PTWONLs can be divided into three categories, with surface states hosting different shapes and positions in the Brillouin zone (BZ). Specifically, semiconducting Rb2Sn2O3 was found to exhibit perfect PTWONLs in its phonon spectrum, which fills up one of the categories. Numerical calculations showed that the drumhead-like surface states exist on the (010) surface and six PTWONLs appear in the first BZ due to the C3 rotation symmetry in the crystal structure. Their topological nontrivial nature was confirmed by calculating the Berry phase and by the linear phononic bands around the Weyl points. These theoretical findings provide a deep understanding into the phononic Weyl-open-nodal-line physics, and a promising candidate for experimental verification.

16.
J Nat Prod ; 82(6): 1510-1517, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31150241

RESUMO

Chromatographic purification of the roots of Daphne genkwa led to 11 new guaiane-type sesquiterpenoids (1-11), named genkwanoids A-K, and six known analogues (12-17). A comprehensive set of spectroscopic methods including IR, UV, HRESIMS, and 1D/2D NMR were used to elucidate the structures and relative configurations of 1-11. The absolute configurations were determined by the optical rotation calculations and the modified Mosher's method. The possible biosynthetic pathways for 1-11 are proposed. Furthermore, the neuroprotective effects of 1-17 on H2O2-induced damage in human neuroblastoma SH-SY5Y cells were screened using an MTT assay. Compounds 9, 10, and 16 exhibited moderate neuroprotective effects, with survival rates of 79.34%, 79.94%, and 75.64% after treatment with 12.5 µM, values that were comparable to the positive control, Trolox (78.65%). Furthermore, annexin V-FITC/PI staining of cells treated with 9, 10, and 16 showed that the neuroprotective effects of these compounds may arise from inhibiting cell apoptosis.

17.
Wideochir Inne Tech Maloinwazyjne ; 14(2): 187-194, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31118982

RESUMO

Introduction: The role of laparoscopic selective esophagogastric devascularization and splenectomy (LSEGDS) in the treatment of esophagogastric variceal bleeding and hypersplenism in patients with cirrhotic portal hypertension has not been well studied. Aim: To investigate the safety and efficacy of LSEGDS for esophagogastric variceal bleeding and hypersplenism in patients with cirrhotic portal hypertension. Material and methods: From May 2011 to December 2014, 74 patients with portal hypertension resulting from liver cirrhosis underwent surgery for gastroesophageal variceal bleeding and hypersplenism. Forty-one of these patients underwent laparoscopic esophagogastric devascularization and splenectomy (LEGDS), and the others underwent LSEGDS. A retrospective comparative analysis of clinical data was conducted between the two groups, including clinical characteristics, laboratory data, operative morbidity and mortality, and outcomes of follow-up. Results: The operation was completed successfully in all the patients, except that conversion was required in one patient in the LEGDS group. The operating time was similar in both groups (p = 0.579). The intraoperative blood loss was lower in the LSEGDS group (p = 0.011). Postoperative complications showed no significant difference between the two groups regarding mortality rate, pleural effusion, pancreatic injury, pulmonary infection, liver dysfunction, or postoperative abdominal bleeding. Postoperative platelet counts increased significantly more in the LEGDS group than in the LSEGDS group (p = 0.004). There were no significant differences in the long-term follow-up data, such as incidence of rebleeding, portal vein thrombosis, hepatic encephalopathy and survival (p > 0.05). Conclusions: The LSEGDS is a safe and effective procedure for management of cirrhotic portal hypertension, especially in patients with visible paraesophageal veins.

18.
Nat Commun ; 10(1): 721, 2019 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760721

RESUMO

Broadly neutralizing antibodies (bNAbs) represent a promising alternative to antiretroviral drugs for HIV-1 prevention and treatment. Selected antibodies to the CD4-binding site bolster envelope trimer binding via quaternary contacts. Here, we rationally engraft a new paratope, i.e., the extended heavy-chain framework region 3 (FR3) loop of VRC03, which mediates quaternary interaction, onto several potent bNAbs, enabling them to reach an adjacent gp120 protomer. The interactive quaternary surface is delineated by solving the crystal structure of two FR3 loop-chimeric antibodies. Chimerization enhances the neutralizing activity of several potent bNAbs against a majority of global HIV-1 strains. Compared to unmodified antibodies, chimeric antibodies display lower autoreactivity and prolonged in vivo half-life in huFcRn mice and rhesus macaques. Thus, paratope engraftment may be used to expand the epitope repertory of natural antibodies, improving their functionality for disease prevention and treatment.


Assuntos
Anticorpos Neutralizantes/química , Anticorpos Neutralizantes/imunologia , Sítios de Ligação de Anticorpos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Animais , Anticorpos Neutralizantes/genética , Sítios de Ligação de Anticorpos/genética , Modelos Animais de Doenças , Mapeamento de Epitopos , Epitopos , Feminino , Células HEK293 , Anticorpos Anti-HIV/química , Anticorpos Anti-HIV/imunologia , Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/genética , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/prevenção & controle , Humanos , Região Variável de Imunoglobulina/química , Região Variável de Imunoglobulina/genética , Região Variável de Imunoglobulina/imunologia , Macaca mulatta , Camundongos , Camundongos Transgênicos , Modelos Moleculares , Mutagênese Sítio-Dirigida , Conformação Proteica
19.
Bioorg Chem ; 84: 269-275, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30529844

RESUMO

Alzheimer's disease (AD) is characterized by the progressive accumulation of extracellular ß-amyloid (Aß) aggregates. Recently, lignans and phenylpropanoids are attracting increasing attention to discovery useful agents of inhibition on Aß aggregation. In the present study, to develop potential agents for slowing the progression of AD, Prunus tomentosa seeds were selected as a raw material for bioactive compounds, which led to the separation of two pairs of new enantiomeric lignans and phenylpropanoids using chiral HPLC. The planar structures of these compounds were elucidated by spectroscopic data analyses. And their absolute configurations were determined by comparing of experimental and calculated electronic circular dichroism (ECD). The biosynthesis pathway was also discussed. Additionally, the inhibitory activity on Aß aggregation of all optical pure compounds was tested by thioflavin T (ThT) assay. The isolates (1a, 1b, 2a and 2b) showed more potent inhibitory activity than positive control curcumin with inhibitory rate of 73.89 ±â€¯3.41% 78.69 ±â€¯1.50%, 63.25 ±â€¯2.68%, and 67.13 ±â€¯0.90% at 20 µM, respectively. More importantly, the inhibition profiles were explained by molecular dynamics and docking simulation studies.


Assuntos
Peptídeos beta-Amiloides/antagonistas & inibidores , Lignanas/química , Propanóis/química , Prunus/metabolismo , Peptídeos beta-Amiloides/metabolismo , Sítios de Ligação , Humanos , Lignanas/metabolismo , Lignanas/farmacologia , Simulação de Acoplamento Molecular , Fragmentos de Peptídeos/antagonistas & inibidores , Fragmentos de Peptídeos/metabolismo , Propanóis/metabolismo , Propanóis/farmacologia , Agregados Proteicos/efeitos dos fármacos , Estrutura Terciária de Proteína , Prunus/química , Sementes/química , Sementes/metabolismo
20.
PeerJ ; 6: e6061, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30564521

RESUMO

Background: Colorectal cancer remains a serious public health problem due to the poor prognosis. In the present study, we attempted to develop and validate a prognostic signature to predict the individual mortality risk in colorectal cancer patients. Materials and Methods: The original study datasets were downloaded from The Cancer Genome Atlas database. The present study finally included 424 colorectal cancer patients with wholly gene expression information and overall survival information. Results: A nine-lncRNA prognostic signature was built through univariate and multivariate Cox proportional regression model. Time-dependent receiver operating characteristic curves in model cohort demonstrated that the Harrell's concordance indexes of nine-lncRNA prognostic signature were 0.768 (95% CI [0.717-0.819]), 0.778 (95% CI [0.727-0.829]) and 0.870 (95% CI [0.819-0.921]) for 1-year, 3-year and 5-year overall survival respectively. In validation cohort, the Harrell's concordance indexes of nine-lncRNA prognostic signature were 0.761 (95% CI [0.710-0.812]), 0.801 (95% CI [0.750-0.852]) and 0.883 (95% CI [0.832-0.934]) for 1-year, 3-year and 5-year overall survival respectively. According to the median of nine-lncRNA prognostic signature score in model cohort, 424 CRC patients could be stratified into high risk group (n = 212) and low risk group (n = 212). Kaplan-Meier survival curves showed that the overall survival rate of high risk group was significantly lower than that of low risk group (P < 0.001). Discussion: The present study developed and validated a nine-lncRNA prognostic signature for individual mortality risk assessment in colorectal cancer patients. This nine-lncRNA prognostic signature is helpful to evaluate the individual mortality risk and to improve the decision making of individualized treatments in colorectal cancer patients.

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