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1.
Opt Express ; 32(4): 6644-6657, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-38439363

RESUMO

We proposed the cascaded high contrast grating (CHCG) structure to enhance surface sensing capabilities through bound states in the continuum (BICs). Utilizing the finite element method (FEM) and rigorous coupled-wave analysis (RCWA), we studied the dispersion relations, far-field contribution CHCGs, and near-field distributions of BICs corresponding to resonance peaks at different wavelengths. Results demonstrate the ability to precisely control symmetry-protected BIC (SP-BIC) and Friedrich-Wintgen BIC (FW-BIC) resonance peaks by altering incident angles and structural parameters, enhancing structure robustness and tunability. Significantly, modes 1 and 2 have demonstrated substantial enhancement in surface refractive index sensing, achieving highest sensitivities at 51 nm/RIU and the figure of merit reaching 490.8 RIU-1, indicating notable advancement in detecting subtle surface changes. In contrast, mode 3 has shown robust performance in bulk refractive index sensing, achieving a sensitivity of 602 nm/RIU and a figure of merit of 5189.65 RIU-1. These findings underscore the significant potential of the structure as a high-performance integrated sensor, particularly for precise environmental and biological monitoring in surface refractive index sensing.

2.
Antonie Van Leeuwenhoek ; 117(1): 81, 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38777900

RESUMO

A Gram-stain-negative, aerobic, non-motile, catalase- and oxidase-positive, pale orange, rod-shaped strain EF6T, was isolated from a natural wetland reserve in Hebei province, China. The strain grew at 25-37 °C (optimum, 30 °C), pH 5-9 (optimum, pH 7), and in the presence of 1.0-4.0% (w/v) NaCl (optimum, 2%). A phylogenetic analysis based on 16S rRNA gene sequence revealed that strain EF6T belongs to the genus Paracoccus, and the closest members were Paracoccus shandongensis wg2T with 98.1% similarity, Paracoccus fontiphilus MVW-1 T (97.9%), Paracoccus everestensis S8-55 T (97.7%), Paracoccus subflavus GY0581T (97.6%), Paracoccus sediminis CMB17T (97.3%), Paracoccus caeni MJ17T (97.0%), and Paracoccus angustae E6T (97.0%). The genome size of strain EF6T was 4.88 Mb, and the DNA G + C content was 65.3%. The digital DNA-DNA hybridization, average nucleotide identity, and average amino acid identity values between strain EF6T and the reference strains were all below the threshold limit for species delineation (< 32.8%, < 88.0%, and < 86.7%, respectively). The major fatty acids (≥ 5.0%) were summed feature 8 (86.3%, C18:1 ω6c and/or C18:1 ω7c) and C18:1 (5.0%) and the only isoprenoid quinone was Q-10. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids, five unidentified phospholipids, and an unidentified aminolipid. Strain EF6T displays notable resistance to benzoate and selenite, with higher tolerance levels (25 g/L for benzoate and 150 mM for selenite) compared to the closely related species. Genomic analysis identified six benzoate resistance genes (acdA, pcaF, fadA, pcaC, purB, and catA) and twenty selenite resistance and reduction-related genes (iscR, ssuB, ssuD, selA, selD and so on). Additionally, EF6T possesses unique genes (catA, ssuB, and ssuC) absent in the closely related species for benzoate and selenite resistance. Its robust resistance to benzoate and selenite, coupled with its genomic makeup, make EF6T a promising candidate for the remediation of both organic and inorganic pollutants. It is worth noting that the specific resistance phenotypes described above were not reported in other novel species in Paracoccus. Based on the results of biochemical, physiological, phylogenetic, and chemotaxonomic analyses, combined with comparisons of the 16S rRNA gene sequence and the whole genome sequence, strain EF6T is considered to represent a novel species of the genus Paracoccus within the family Rhodobacteraceae, for which the name Paracoccus benzoatiresistens sp. nov. is proposed. The type strain is EF6T (= GDMCC 1.3400 T = JCM 35642 T = MCCC 1K08702T).


Assuntos
Composição de Bases , DNA Bacteriano , Ácidos Graxos , Paracoccus , Filogenia , RNA Ribossômico 16S , Áreas Alagadas , Paracoccus/genética , Paracoccus/classificação , Paracoccus/isolamento & purificação , Paracoccus/metabolismo , Paracoccus/efeitos dos fármacos , RNA Ribossômico 16S/genética , Ácidos Graxos/metabolismo , Ácidos Graxos/química , DNA Bacteriano/genética , China , Selenito de Sódio/metabolismo , Técnicas de Tipagem Bacteriana , Fosfolipídeos/análise , Análise de Sequência de DNA , Hibridização de Ácido Nucleico , Oxirredução , Farmacorresistência Bacteriana
3.
Eur Arch Otorhinolaryngol ; 281(5): 2293-2301, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38015248

RESUMO

OBJECTIVES: In several disorders, the monocyte to high-density lipoprotein ratio (MHR) has been considered a biomarker of systemic inflammation and oxidative stress. However, its role in Bell's palsy (BP) remains unclear. This study investigates the relationship between elevated MHR and poor recovery in BP patients. METHODS: The clinical data of 729 BP patients were analyzed retrospectively. The House-Brackmann Facial Nerve Grading System (H-B) was utilized to assess the severity of facial motor dysfunction during admission and the follow-up period after discharge. According to the 6 months follow-up data, H-B grades 1-2 were classified as recovered (n = 557), and H-B grades 3-6 as unrecovered (n = 172). The patients were split into MHR ≤ 0.26 (n = 361) and MHR > 0.26 (n = 368) groups based on the median MHR to further analyze the connection between different MHRs and prognosis. RESULTS: The level of MHR was substantially greater in the unrecovered group of BP patients than in the restored group (medians[interquartile range], 0.32[0.20, 0.49] vs 0.24[0.11, 0.39], P < 0.001). MHR was an independent risk factor for BP prognosis as indicated by the multivariate logistic regression analysis (OR = 4.467, 95% CI = 1.875-10.646, P = 0.001). The area under the curve (AUC) was 0.615 (95% CI = 0.566-0.664, P < 0.001). The initial H-B score did not differ significantly between MHR ≤ 0.26 (n = 361) and MHR > 0.26 (n = 368) groups. However, after 6 months of follow-up, the high-MHR group's H-B score was considerably greater than the low-MHR group's. CONCLUSIONS: MHR is expected to be an accessible and effective biomarker of BP. In BP patients, elevated MHR is related to an increased chance of poor recovery.


Assuntos
Paralisia de Bell , Paralisia Facial , Humanos , Paralisia de Bell/diagnóstico , Monócitos , Lipoproteínas HDL , Estudos Retrospectivos , Prognóstico , Biomarcadores
4.
Opt Express ; 31(9): 13959-13969, 2023 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-37157270

RESUMO

We propose a cascaded asymmetric resonant compound grating (ARCG) for high-performance dual-band refractive index sensing. The physical mechanism of the sensor is investigated using a combination of temporal coupled-mode theory (TCMT) and ARCG eigenfrequency information, which is verified by rigorous coupled-wave analysis (RCWA). The reflection spectra can be tailored by changing the key structural parameters. And by altering the grating strip spacing, a dual-band quasi-bound state in the continuum can be achieved. The simulation results show that the highest sensitivity of the dual-band sensor is 480.1 nm/RIU, and its figure of merit is 4.01 × 105. The proposed ARCG has potential application prospects for high-performance integrated sensors.

5.
Opt Express ; 31(6): 10645-10656, 2023 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-37157607

RESUMO

We propose a deep learning demodulation method based on a long short-term memory (LSTM) neural network for fiber Bragg grating (FBG) sensing networks. Interestingly, we find that both low demodulation error and distorted spectrum recognition are realized using the proposed LSTM-based method. Compared with conventional demodulation methods, including Gaussian-fitting, convolutional neural network, and the gated recurrent unit, the proposed method improves the demodulation accuracy being close to 1 pm and achieves a demodulation time of 0.1s for 128-FBG sensors. Furthermore, our approach can realize 100% accuracy of distorted spectra recognition and complete the location of spectra with spectrally encoded FBG sensors.

6.
Opt Express ; 31(22): 36228-36235, 2023 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-38017777

RESUMO

A high-performance optical sensor with a vertical cavity structure comprising high-contrast gratings (HCGs) and a distributed Bragg reflector was designed. The structure has two peaks with different mechanisms, among which the first peak is formed by breaking the symmetry of the structure and coupling between the incident wave and the symmetric protection mode. The joint action of the HCG resonance and Fabry-Perot resonance formed a second peak. Moreover, changing the structural parameters, such as the grating width, period, and cavity length, can tune the spectral reflection dips. The sensitivity of the designed structure was as high as 674 nm/RIU, and the corresponding figure of merit was approximately 34741. The presented gas sensor provides a method for applying a vertical cavity structure to the sensing domain.

7.
Opt Express ; 31(25): 41313-41325, 2023 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-38087533

RESUMO

We propose a three-layer ring architecture with enhanced reconfigurable capabilities for fiber Bragg grating (FBG) sensor networks. The proposed network is capable of self-healing when three fiber links fail. In addition to self-healing, soft faults in the FBG sensors can be detected using a multi-classification support vector machine (multi-class SVM) algorithm. The detection accuracy reached 99%. Additionally, we used an artificial neural network (ANN) reliability estimation model to estimate the reliability of the FBG self-healing network. The results show that the ANN reliability analysis model can accurately estimate the reliability of the architecture at a reasonable cost.

8.
Liver Int ; 43(2): 442-451, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35797245

RESUMO

BACKGROUND AND AIMS: We hypothesized that artificial intelligence (AI) models are more precise than standard models for predicting outcomes in acute-on-chronic liver failure (ACLF). METHODS: We recruited ACLF patients between 2009 and 2020 from APASL-ACLF Research Consortium (AARC). Their clinical data, investigations and organ involvement were serially noted for 90-days and utilized for AI modelling. Data were split randomly into train and validation sets. Multiple AI models, MELD and AARC-Model, were created/optimized on train set. Outcome prediction abilities were evaluated on validation sets through area under the curve (AUC), accuracy, sensitivity, specificity and class precision. RESULTS: Among 2481 ACLF patients, 1501 in train set and 980 in validation set, the extreme gradient boost-cross-validated model (XGB-CV) demonstrated the highest AUC in train (0.999), validation (0.907) and overall sets (0.976) for predicting 30-day outcomes. The AUC and accuracy of the XGB-CV model (%Δ) were 7.0% and 6.9% higher than the standard day-7 AARC model (p < .001) and 12.8% and 10.6% higher than the day 7 MELD for 30-day predictions in validation set (p < .001). The XGB model had the highest AUC for 7- and 90-day predictions as well (p < .001). Day-7 creatinine, international normalized ratio (INR), circulatory failure, leucocyte count and day-4 sepsis were top features determining the 30-day outcomes. A simple decision tree incorporating creatinine, INR and circulatory failure was able to classify patients into high (~90%), intermediate (~60%) and low risk (~20%) of mortality. A web-based AARC-AI model was developed and validated twice with optimal performance for 30-day predictions. CONCLUSIONS: The performance of the AARC-AI model exceeds the standard models for outcome predictions in ACLF. An AI-based decision tree can reliably undertake severity-based stratification of patients for timely interventions.


Assuntos
Insuficiência Hepática Crônica Agudizada , Humanos , Insuficiência Hepática Crônica Agudizada/diagnóstico , Inteligência Artificial , Creatinina , Prognóstico , Fatores de Tempo
9.
Scand J Gastroenterol ; 58(12): 1514-1522, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37545358

RESUMO

BACKGROUND: Graves' hyperthyroidism (GH) is often accompanied by mild to moderate liver injury, but severe hepatic dysfunction (SHD) is relatively rare. Whether patients with GH-related SHD can be treated with methimazole (MMI) remains controversial. This study aimed to determine the clinical characteristics and to evaluate the role of low-dose MMI for such patients. METHODS: 33 patients with GH-related SHD were selected for this retrospective study in the Fifth Medical Center of Chinese PLA General Hospital from January 2017 to July 2022. The clinical manifestations, therapeutic responses, and effectiveness of MMI were evaluated. RESULTS: Systemic jaundice (100.0%), yellow urine (100.0%), fatigue (87.9%), and goiter (66.7%) were the main symptoms. Total bilirubin (TBIL) had no linear correlation with free triiodothyronine (FT3) (r = -0.023, p = .899), free thyroxine (FT4) (r = 0.111, p = .540), T3 (r = -0.144, p = .425), and T4 (r = 0.037, p = .837). On the 14th day after admission, FT3, FT4, T3, T4, TBIL, direct bilirubin (DBIL), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), and international normalized ratio (INR) decreased compared with the baseline (p < .05). The decrease rates of FT3, FT4, T3, T4, TBIL, and DBIL in the MMI group were higher than those in the non-MMI group (p < .05). The improvement rate of the MMI group (77.8%) was higher than that of the non-MMI group (9.5%, p = .001). MMI treatment is an independent predictor affecting the early improvement of patients (OR = 0.022, p = .010). CONCLUSIONS: The main clinical manifestations of patients with GH-related SHD were symptoms related to liver disease. Low-dose MMI was safe and effective for them.


Assuntos
Doença de Graves , Hipertireoidismo , Hepatopatias , Humanos , Metimazol/uso terapêutico , Antitireóideos/uso terapêutico , Estudos Retrospectivos , Doença de Graves/complicações , Doença de Graves/tratamento farmacológico , Doença de Graves/induzido quimicamente , Tiroxina/uso terapêutico , Hipertireoidismo/complicações , Hipertireoidismo/tratamento farmacológico , Hipertireoidismo/induzido quimicamente , Hepatopatias/complicações , Bilirrubina
10.
Cell Biol Toxicol ; 39(6): 2569-2586, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37953354

RESUMO

BACKGROUND: Urinary extracellular vesicles (EVs) have gained increasing interest in recent years as a potential source of noninvasive biomarkers of diseases related to urinary organs, but knowledge of the mechanism is still limited. The current study sought to clarify the mechanism of urinary EVs behind di-(2-ethylhexyl) phthalate (DEHP)-induced hypospadias via PFN2 delivery. METHOD: PFN2 expression in hypospadias was predicted by bioinformatics analysis. Following the induction of a hypospadias rat model using DEHP, rats were injected with EVs and/or underwent alteration of PFN2 and TGF-ß1 to assess their effects in vivo. The extracted rat urothelial cells (UECs) were co-cultured with EVs extracted from urine for in vitro experiments. RESULT: Microarray analysis predicted poor PFN2 expression in hypospadias. Upregulated PFN2 was found in urinary EVs, and restrained epithelial-mesenchymal transition (EMT) was observed in DEHP-exposed rats. Urinary EVs or PFN2 overexpression increased SMAD2, SMAD3, and TGF-ß1 protein expression and SMAD2 and SMAD3 phosphorylation in UECs and DEHP-exposed rats. UEC migration, invasion, and EMT were augmented by EV co-culture or upregulation of PFN2. Of note, the silencing of TGF-ß1 counterweighed the effect of PFN2. Besides, EV co-culture or overexpression of PFN2 or TGF-ß1 elevated the body weight, anal-genital distance (AGD), anal-genital index (AGI), and EMT of DEHP-exposed rats. CONCLUSION: In summary, urinary EVs activated the SMAD/TGF-ß1 pathway to induce EMT via PFN2 delivery, thus protecting against DEHP-induced hypospadias. (1) EMT in epithelial cells inhibits DEHP-induced hypospadias. (2) Urine-derived EVs deliver PFN2 to promote EMT in epithelial cells. (3) PFN2 can activate the SMAD/TGF-ß1 signaling axis. (4) Urine-derived EVs can transmit PFN2 to activate the SMAD/TGF-ß1 signaling axis, thus promoting EMT and inhibiting the occurrence of hypospadias.


Assuntos
Dietilexilftalato , Hipospadia , Humanos , Masculino , Ratos , Animais , Fator de Crescimento Transformador beta1/metabolismo , Transição Epitelial-Mesenquimal , Hipospadia/induzido quimicamente , Dietilexilftalato/toxicidade , Profilinas/farmacologia
11.
J Hepatol ; 77(6): 1564-1572, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36038017

RESUMO

BACKGROUND & AIMS: Antiviral therapy improves the clinical outcomes of patients with chronic hepatitis B (CHB), including those with cirrhosis. In the present study, we validated the Baveno VII definition of recompensation and explored the criteria for stable improvement of liver function tests in entecavir-treated patients with CHB-related decompensated cirrhosis. METHODS: In this multicentre prospective study, patients with decompensated (ascites) CHB-related cirrhosis were enrolled and treated with entecavir for 120 weeks. Patients were followed up for clinical events, viral and biochemical tests, and ultrasonography every 6 months. The recompensation rate per Baveno VII criteria was calculated. Multivariate regression models were used to identify the predictors of recompensation. Finally, the criteria for stable improvement of liver function tests were explored. RESULTS: Of the 320 recruited patients, 283 completed the 120-week study, with 261/283 (92.2%) achieving HBV DNA levels <20 IU/ml and 171/283 (60.4%) achieving resolution of ascites, encephalopathy, and absence of recurrent variceal bleeding for at least 12 months. We identified model for end-stage liver disease <10 and/or liver function tests within Child-Pugh Class A (albumin >35 g/L, international normalised ratio <1.50 and total bilirubin <34 µmol/L) as the criteria for stable improvement of liver function tests. Accordingly, 56.2% (159/283) of patients fulfilled the Baveno VII definition of recompensation with a stable improvement of liver function tests defined by the current study. CONCLUSIONS: Our study defined the criteria for a stable improvement of liver function tests required by the Baveno VII definition of recompensation in patients with CHB-related decompensated cirrhosis on antiviral therapy. The criteria derived from this multicentre prospective study warrant further validation in patients with cirrhosis of other aetiologies. LAY SUMMARY: Decompensation of cirrhosis marks the point at which the liver is no longer able to function normally (and symptoms become apparent). Recently the idea of recompensation was proposed for individuals who may experience an improvement in liver function if the underlying cause of their liver disease is addressed (e.g. antivirals for viral cirrhosis). Herein, we show that over 50% of patients with hepatitis B-related decompensated cirrhosis treated with antivirals could recompensate and we propose laboratory criteria which could be used to define recompensation.


Assuntos
Doença Hepática Terminal , Varizes Esofágicas e Gástricas , Hepatite B , Humanos , Ascite , Estudos Prospectivos , Hemorragia Gastrointestinal , Índice de Gravidade de Doença , Antivirais/uso terapêutico , Cirrose Hepática/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/tratamento farmacológico
12.
Eur Radiol ; 32(6): 4046-4055, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35066633

RESUMO

OBJECTIVES: To evaluate the diagnostic value of computer-aided diagnosis (CAD) software on ultrasound in distinguishing benign and malignant breast masses and avoiding unnecessary biopsy. METHODS: This prospective, multicenter study included patients who were scheduled for pathological diagnosis of breast masses between April 2019 and November 2020. Ultrasound images, videos, CAD analysis, and BI-RADS were obtained. The AUC, accuracy, sensitivity, specificity, PPV, and NPV were calculated and compared with radiologists. RESULTS: Overall, 901 breast masses in 901 patients were enrolled in this study. The accuracy, sensitivity, specificity, PPV and NPV of CAD software were 89.6%, 94.2%, 87.0%, 80.4%, and 96.3, respectively, in the long-axis section; 89.0%, 91.4%, 87.7%, 80.8%, and 94.7%, respectively, in the short-axis section. With BI-RADS 4a as the cut-off value, CAD software has a higher AUC (0.906 vs 0.734 vs 0.696, all p < 0.001) than both experienced and less experienced radiologists. With BI-RADS 4b as the cut-off value, CAD software showed better AUC than less experienced radiologists (0.906 vs 0.874, p < 0.001), but not superior to experienced radiologists (0.906 vs 0.883, p = 0.057). After the application of CAD software, the unnecessary biopsy rate of BI-RADS categories 4 and 5 was significantly decreased (33.0% vs 11.9%, 37.8% vs 14.5%), and the malignant rate of biopsy in category 4a was significantly increased (11.6% vs 40.7%, 7.4% vs 34.9%, all p < 0.001). CONCLUSIONS: CAD software on ultrasound can be used as an effective auxiliary diagnostic tool for differential diagnosis of benign and malignant breast masses and reducing unnecessary biopsy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03887598) KEY POINTS: • Prospective multicenter study showed that computer-aided diagnosis software provides greater diagnostic confidence for differentiating benign and malignant breast masses. • Computer-aided diagnosis software can help radiologists reduce unnecessary biopsy. • The management of patients with breast masses becomes more appropriate.


Assuntos
Neoplasias da Mama , Mama , Mama/diagnóstico por imagem , Mama/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Computadores , Diagnóstico por Computador/métodos , Feminino , Humanos , Estudos Prospectivos , Sensibilidade e Especificidade , Ultrassonografia Mamária/métodos
13.
Org Biomol Chem ; 20(21): 4376-4384, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-35579069

RESUMO

Three novel phomactin diterpenes neocucurbins A-C (1-3) and their derivatives, neocucurbins D-G (4-7), were isolated from the marine-derived fungus Neocucurbitaria unguis-hominis FS685. Among them, neocucurbins A-C represent the first examples of the phomactin family with an unprecedented skeleton sharing a novel polyoxygen-hetero 5/6/12 or 5/6/13 fused tricyclic ring system; whereas neocucurbins D-G feature a 5/6 fused bicyclic ring system with the opening of the macrocyclic ring, which was found in the phomactin family for the first time. Moreover, spectroscopic data analyses, single-crystal X-ray diffraction experiments, and ECD calculations were conducted to illustrate the absolute configurations of their structures. Furthermore, all seven compounds (1-7) were evaluated for their cytotoxic and antimicrobial activities.


Assuntos
Antineoplásicos , Ascomicetos , Diterpenos , Cristalografia por Raios X , Diterpenos/química , Estrutura Molecular
14.
Mol Biol Rep ; 49(9): 8715-8725, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35781603

RESUMO

BACKGROUND: Presently, liver transplantation is the only treatment strategy for liver failure (LF). Although granulocyte-colony stimulating factor (G-CSF) exhibits protective functions in LF, it is not clear whether it directly affects the liver cells. METHODS AND RESULTS: We established an injured liver cell model and observed that G-CSF treatment promoted cell viability and enhanced Ki67 and VEGF-A expression. Thereafter, human umbilical vein endothelial cells (HUVECs) were cultured in a conditioned medium collected from the G-CSF-treated injured liver cells. HUVECs' proliferation and tubule formation were promoted. Furthermore, in an injured liver mouse model, confirmed via haematoxylin-eosin staining, we evaluated serum alanine aminotransferase activity, Ki67 expression, and microvessel density (MVD). G-CSF treatment significantly relieved liver injury, upregulated Ki67 expression, and enhanced MVD in the injured mouse liver tissue. Additionally, AKT and ERK signal targets were explored, and it was demonstrated that the effects of G-CSF on injured liver cells were mediated through the AKT and ERK signalling pathways. CONCLUSIONS: G-CSF promotes injured liver viability and angiogenesis by directly affecting injured liver cells via the AKT and ERK signalling pathways. These findings improve our understanding of the role of G-CSF in recovery from LF.


Assuntos
Fator Estimulador de Colônias de Granulócitos , Proteínas Proto-Oncogênicas c-akt , Animais , Fator Estimulador de Colônias de Granulócitos/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Antígeno Ki-67 , Fígado/metabolismo , Camundongos , Neovascularização Patológica/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo
15.
J Nat Prod ; 85(8): 1967-1975, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-35866554

RESUMO

Neocucurbols A-D (1-4) are diterpene derivatives that possess a complex 6/6/5/5/6 polycyclic ring system with a characteristic tetrahedrofuran bridge ring skeleton. Neocucurbols E-H (5-8) are diterpenes that feature a 6/8/6 tricyclic ring system. Their structures were unambiguously determined by detailed spectroscopic analyses, X-ray diffractions studies, and ECD calculations. All compounds (1-8) were evaluated for in vitro antimicrobial and cytotoxic activities.


Assuntos
Anti-Infecciosos , Ascomicetos , Diterpenos , Diterpenos/química , Diterpenos/farmacologia , Estrutura Molecular
16.
J Cell Mol Med ; 25(9): 4275-4286, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33834618

RESUMO

Long non-coding RNAs (lncRNAs) are a novel class of regulators in multiple cancer biological processes. However, the functions of lncRNAs in pancreatic ductal adenocarcinoma (PDAC) remain largely unknown. In this study, we identified PWAR6 as a frequently down-regulated lncRNA in PDAC samples as well as a panel of pancreatic cancer cell lines. Down-regulated PWAR6 was associated with multiple clinical outcomes, including advanced tumour stage, distant metastasis, and overall survival of PDAC patients. In our cell-based assays, ectopic expression of PWAR6 dramatically repressed PDAC cells proliferation, invasion and migration, accelerated apoptosis, and induced cell cycle arrest at G0/G1 phase. In contrast, depletion of PWAR6 mediated by siRNA exhibited opposite effects on PDAC cell behaviours. In vivo study further validated the anti-tumour role of PWAR6 in PDAC. By taking advantage of available online sources, we also identified YAP1 as a potential PWAR6 target gene. Negative correlation between YAP1 and PWAR6 expressions were observed in both online database and our PDAC samples. Notably, rescue experiments further indicated that YAP1 is an important downstream effector involved in PWAR6-mediated functions. Mechanistically, PWAR6 could bind to methyltransferase EZH2, a core component of Polycomb Repressive Complex 2 (PRC2) in regulating gene expression, and scaffold EZH2 to the promoter region of YAP1, resulting in epigenetic repression of YAP1. In conclusion, our data manifest the vital roles of PWAR6 in PDAC tumorigenesis and underscore the potential of PWAR6 as a promising target for PDAC diagnosis and therapy.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/antagonistas & inibidores , Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/patologia , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/patologia , RNA Longo não Codificante/genética , Fatores de Transcrição/antagonistas & inibidores , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Movimento Celular , Proliferação de Células , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Prognóstico , Taxa de Sobrevida , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas de Sinalização YAP
17.
Opt Express ; 29(18): 29458-29465, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34615055

RESUMO

We proposed a high-performance integrated optical sensor based on a stacked resonant compound grating (SRCG). The transmission spectrum of a SRCG is investigated by the theoretical model that combines the coupled mode theory with the eigenmode information of the grating structures. It is found that the spectral width of the SRCG is controlled by changing its structural parameters such as the strip depth, the period of the grating, and cavity length. The simulation results, which are verified by finite element method (FEM), show that the sensitivity of the sensor is 401.8 nm/RIU with its figure of merit (FOM) as high as 57404. The presented sensor is a promising application for high-performance biosensing.

18.
Liver Int ; 41(5): 1083-1096, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33529450

RESUMO

BACKGROUND AND AIM: Plasma-exchange (PE) has improved survival in acute liver failure by ameliorating systemic inflammatory response syndrome (SIRS). We evaluated PE and compared it to Fractional Plasma Separation and Adsorption (FPSA) and standard medical treatment (SMT) in a large multinational cohort of ACLF patients. METHODS: Data were prospectively collected from the AARC database and analysed. Matching by propensity risk score (PRS) was performed. Competing risk survival analysis was done to identify deaths because of multiorgan failure (MOF). In a subset of 10 patients, we also evaluated the mechanistic basis of response to PE. RESULTS: ACLF patients (n = 1866, mean age 44.3 ± 12.3 yrs, 93% males, 65% alcoholics) received either artificial liver support (ALS) (n = 162); [PE (n = 131), FPSA (n = 31)] or were continued on standard medical therapy (SMT) (n = 1704). In the PRS-matched cohort (n = 208, [ALS-119; PE-94, FPSA-25)], SMT-89). ALS therapies were associated with a significantly higher resolution of SIRS (Odd's ratio 9.23,3.42-24.8), lower and delayed development of MOF (Hazard ratio 7.1, 4.5-11.1), and lower liver-failure-related deaths as compared to FPSA and SMT (P < .05). PE cleared inflammatory cytokines, damage-associated molecular patterns, and endotoxin in all patients. Responders improved monocyte phagocytic function and mitochondrial respiration and increased the anti-inflammatory cytokine interleukin-1 receptor antagonist (IL-1RA) compared to non-responders. PE was associated with lesser adverse effects as compared to FPSA. CONCLUSIONS: PE improves systemic inflammation and lowers the development of MOF in patients with ACLF. Plasma-exchange provides significant survival benefit over FPSA and could be a preferred modality of liver support for ACLF patients.


Assuntos
Insuficiência Hepática Crônica Agudizada , Insuficiência Hepática Crônica Agudizada/terapia , Adulto , Feminino , Humanos , Inflamação/terapia , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Pontuação de Propensão
19.
Liver Int ; 41(1): 150-157, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32970356

RESUMO

BACKGROUND: Metabolic risk factors may impact the severity and outcome of alcoholic liver disease. The present study evaluated this effect in patients with alcohol-associated acute-on-chronic liver failure (ACLF). METHODOLOGY: One thousand two hundred and sixteen prospectively enrolled patients with ACLF (males 98%, mean age 42.5 ± 9.4 years, mean CTP, MELD and AARC scores of 12 ± 1.4, 29.7 ± 7 and 9.8 ± 2 respectively) from the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) database were analysed retrospectively. Patients with or without metabolic risk factors were compared for severity (CTP, MELD, AARC scores) and day 30 and 90 mortality. Information on overweight/obesity, type 2 diabetes mellitus (T2DM), hypertension and dyslipidaemia were available in 1028 (85%), 1019 (84%), 1017 (84%) and 965 (79%) patients respectively. RESULTS: Overall, 392 (32%) patients died at day 30 and 528 (43%) at day 90. Overweight/obesity, T2DM, hypertension and dyslipidaemia were present in 154 (15%), 142 (14%), 66 (7%) and 141 (15%) patients, respectively, with no risk factors in 809 (67%) patients. Patients with overweight/obesity had higher MELD scores (30.6 ± 7.1 vs 29.2 ± 6.9, P = .007) and those with dyslipidaemia had higher AARC scores (10.4 ± 1.2 vs 9.8 ± 2, P = .014). Overweight/obesity was associated with increased day 30 mortality (HR 1.54, 95% CI 1.06-2.24, P = .023). None of other metabolic risk factors, alone or in combination, had any impact on disease severity or mortality. On multivariate analysis, overweight or obesity was significantly associated with 30-day mortality (aHR 1.91, 95% CI 1.41-2.59, P < .001), independent of age, CTP, MELD and AARC scores. CONCLUSION: Overweight/obesity and dyslipidaemia increase the severity of alcohol-associated ACLF, and the former also increases the short-term mortality in these patients.


Assuntos
Insuficiência Hepática Crônica Agudizada , Diabetes Mellitus Tipo 2 , Insuficiência Hepática Crônica Agudizada/epidemiologia , Insuficiência Hepática Crônica Agudizada/etiologia , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Fatores de Risco
20.
J Nanobiotechnology ; 19(1): 349, 2021 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-34717634

RESUMO

One of the main challenges of tissue-engineered vascular prostheses is restenosis due to intimal hyperplasia. The aim of this study is to develop a material for scaffolds able to support cell growth while tolerating physiological conditions and maintaining the patency of carotid artery model. Tubular hyaluronic acid (HA)-functionalized collagen nanofibrous composite scaffolds were prepared by sequential electrospinning method. The tubular composite scaffold has well-controlled biophysical and biochemical signals, providing a good matrix for the adhesion and proliferation of vascular endothelial cells (ECs), but resisting to platelets adhesion when exposed to blood. Carotid artery replacement experiment from 6-week rabbits showed that the HA/collagen nanofibrous composite scaffold grafts with endothelialization on the luminal surface could maintain vascular patency. At retrieval, the composite scaffold maintained good structural integrity and had comparable mechanical strength as the native artery. This study indicating that electrospun scaffolds combined with cells may become an alternative to prosthetic grafts for vascular reconstruction.


Assuntos
Vasos Sanguíneos , Colágeno/uso terapêutico , Ácido Hialurônico/uso terapêutico , Nanofibras/química , Nanofibras/uso terapêutico , Alicerces Teciduais/química , Animais , Vasos Sanguíneos/patologia , Proliferação de Células , Colágeno/química , Colágeno/farmacologia , Células Endoteliais/metabolismo , Humanos , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Adesividade Plaquetária , Coelhos , Engenharia Tecidual/métodos
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