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BACKGROUND: Heart failure is a syndrome with complex clinical manifestations. Due to increasing population aging, heart failure has become a major medical problem worldwide. In this study, we used the MIMIC-III public database to extract the temporal and spatial characteristics of electrocardiogram (ECG) signals from patients with heart failure. METHODS: We developed a NYHA functional classification model for heart failure based on a deep learning method. We introduced an integrating attention mechanism based on the CNN-LSTM-SE model, segmenting the ECG signal into 2 to 20 s long segments. Ablation experiments showed that the 12 s ECG signal segments could be used with the proposed deep learning model for superior classification of heart failure. RESULTS: The accuracy, positive predictive value, sensitivity, and specificity of the NYHA functional classification method were 99.09, 98.9855, 99.033, and 99.649%, respectively. CONCLUSIONS: The comprehensive performance of this model exceeds similar methods and can be used to assist in clinical medical diagnoses.
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Aprendizado Profundo , Insuficiência Cardíaca , Humanos , Arritmias Cardíacas/diagnóstico , Eletrocardiografia/métodos , Insuficiência Cardíaca/diagnóstico , Bases de Dados Factuais , AlgoritmosRESUMO
Work function-tunable borophene-based electrode materials are of significant importance because they promote efficient carrier extraction/injection, thereby enabling electronic devices to achieve maximum energy conversion efficiency. Accordingly, determining the work function of adatom-borophene nanocomposites within a series wherein the adatom is systematically changed will facilitate the design of such materials. In this study, we theoretically determined that the M-B bond length, binding energy, electron transfer between adatoms and BBP, and work function (Ï) are linearly dependent on the ionization potential (IP) and electronegativity for thermodynamically and kinetically stable adatom-α-borophene (M/BBP) systems involving a series of alkali (earth) metal/BBP (M = Li-Cs; Be-Ba) and halogen/BBP (M = F-I), respectively. However, the binding energies of Li/BBP and Be/BBP deviate from these dependencies owing to their super small adatoms and the resulting significantly enhanced effective M-B bonding areas. By interpreting the electron transfer picture among the different parts of M/BBP, we confirmed that metallic M/BBP possesses ionic sp-p and dsp-p M-B bonds in alkali (earth) metal/BBP but covalent-featured ionic p-p interactions in halogen/BBP. In particular, the direct proportionality between IP and Ï for alkali (earth) metal/BBP originates from the synergistic effect of charge rearrangement and the increased induced dipole moment; however, the inverse proportionality between electronegativity and Ï for halogen/BBP arises from the adsorption induced charge redistribution. Our results provide guidance for experimental efforts toward the realization of work function-tunable borophene-based electrodes as well as insight into the bonding rules between various adatoms and α-borophene.
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Increasing the work function of borophene over a large range is crucial for the development of borophene-based anode materials for highly efficient electronic devices. In this study, the effect of fluorine adsorption on the structures and stabilities, particularly on the work function, of α-borophene (BBP), was systematically investigated via first-principles density functional theory. The calculations indicated that BBP was well-stabilized by fluorine adsorption and the work functions of metallic fluorine-adsorbed BBPs (Fn-BBPs) sharply increased with increasing fluorine content. Moreover, the work function of F-BBP was close to that of the frequently used anode material Au and even, for other Fn-BBPs, higher than that of Pt. Furthermore, we have comprehensively discussed the factors, including substrate deformation, charge transfer, induced dipole moment, and Fermi and vacuum energy levels, affecting the improvement of work function. Particularly, we have demonstrated that the charge redistribution of the substrate induced by the bonding interaction between fluorine and the matrix predominantly contributes to the observed increase in the work function. Additionally, the effect of fluorine adsorption on the increase in the work function of BBP was significantly stronger than that of silicene or graphene. Our results concretely support the fact that Fn-BBPs can be extremely attractive anode materials for electronic device applications.
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The fractional oxidation state [M(dmit)2] (dmit2- = 2-thioxo-1, 3-dithiole-4, 5-dithiolate) salts have long attracted attention in the molecular metal area owing to high conductivity and even superconductivity. In this study, we achieved a mixed-valence salt (1) of [Ni(dmit)2]0.5- with monovalent 1,3-N,N-dimethyl-imidazolium (DiMIm+) by a solvent evaporation approach under ambient conditions. The mixed valence of [Ni(dmit)2]0.5- has been characterized by an analysis of the IR spectrum and crystal structure. In the crystal structure of 1, two [Ni(dmit)2]0.5- anions overlap in an eclipsed mode to form a [Ni(dmit)2]21- dimer, featuring a radical bearing an S = 1/2 spin; the dimeric radicals stack into a column along the b axis, and the adjacent columns connect together via the lateral-to-lateral S···S contacts along the a axis, and through the head-to-head S···S contacts along the [101] direction. Salt 1 shows the magnetic behavior of an S = 1/2 Heisenberg antiferromagnetic uniform linear chain with J/kB = -47.5(4) K and a semiconducting feature with σ = 2.52 × 10-3 S cm-1 at 293 K, 2.32 × 10-2 S cm-1 at 373 K, and Ea = 0.22 eV, as well as broadband photoconductivity under irradiation of green and white lights. This study suggests the possibility of designing new photoconductors based on the mixed-valence [Ni(dmit)2]0.5- salt.
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Background Astragalus polysaccharide (APS) had shown great promise in anti-tumour activities in our previous studies. The present study was designed to investigate whether APS has synergistic effect with cisplatin on the growth-inhibitory of human nasopharyngeal carcinoma cell lines and the possible mechanism. Methods Here, nasopharyngeal carcinoma cell lines (CNE-1) were divided into CNE-1 group, Cisplatin treatment group (2 µg/mL Cisplatin), APS treatment group (200 µg/mL APS) and combination group (2 µg/mL Cisplatin and 200 µg/mL APS). The proliferation inhibition rate of CNE-1 cells was determined by Cell Counting Kit-8 (CCK-8) method after treatment with different concentrations of APS for 24, 48, and 72 h. Apoptosis rates and cell cycle retardation of cells were detected by flow cytometry. Cell migration and invasion was evaluated by transwell assay. Western blotting and quantitative (q)RT-PCR were performed to detect the expression of Bcl-2, Bax, caspase-3, matrix metalloproteinase-2 (MMP-2), p53 and matrix metalloproteinase-9 (MMP-9) proteins in CNE-1 cells. Results APS have an inhibition on the proliferation of CNE-1 cells with time and dose dependence manner. Both the APS and combination therapy could promote apoptosis of CNE-1 cells, with the count of cells increased in G0/G1 and S phase while decreased in G2/M phase, and inhibited the migration and invasion of CNE-1 cells. Moreover, co-administration of Cisplatin and APS was more efficacious for the antitumor effect than either agent alone, as evidenced by the significant decrease in MMP-9 level and increase in p53. Conclusion APS, in combination with cisplatin, had significantly synergistic growth-inhibitory effect on nasopharyngeal carcinoma cell lines, which may be related to cell cycle and migration induction.
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Ciclo Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Cisplatino/farmacologia , Carcinoma Nasofaríngeo/tratamento farmacológico , Polissacarídeos/farmacologia , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Combinação de Medicamentos , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
We have previously shown that compound-7g inhibits colorectal cancer cell proliferation and survival by inducing cell cycle arrest and PI3K/AKT/mTOR pathway blockage. However, whether it has the ability to exert antitumor activity in other cancer cells and what is the exact molecular mechanism for its antiproliferation effect remained to be determined. In the present study, compound-7g exhibited strong activity in suppressing proliferation and growth of glioblastoma cells. The inhibitor selectively downregulated F-box protein SKP2 expression and upregulated cell cycle inhibitor p27, and then resulted in G1 cell cycle arrest. Mechanism analysis revealed that compound-7g also provokes the down-regulation of E2F-1, which acts as a transcriptional factor of SKP2. Further results indicated that compound-7g induced an increase of LC3B-II and p62, which causes a suppression of fusion between autophagosome and lysosome. Moreover, compound-7g mediated autophagic flux blockage promoted accumulation of ubiquitinated proteins and then led to endoplasmic reticulum stress. Our study thus demonstrated that pharmacological inactivation of E2F-1-SKP2-p27 axis is a promising target for restricting cancer progression.
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Antineoplásicos/química , Antineoplásicos/farmacologia , Benzimidazóis/química , Isoquinolinas/química , Proteínas Quinases Associadas a Fase S/genética , Autofagia/efeitos dos fármacos , Linhagem Celular Tumoral , Fator de Transcrição E2F1/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , ProteóliseRESUMO
Parasitic pathogens, such as H. pylori (Helicobacter pylori), are considered as primary elements for causing stomach infection and leading to chronic gastritis or ulcers. Here, an unreported urease- and oxidase-producing Neisseria flavescens-like bacteria was isolated from the gastroscopic biopsies of 14C-UBT-positive gastritis patients. The isolate expressed the activity of urease, which is a pathogenic factor and considered as a reliable marker for diagnosis of H. pylori infection. However, the isolate didn't express the key functional genes of H. pylori including vacA and hpaA, and also the morphological feature of isolate was significantly different with H. pylori. Eventually, the 16S rDNA of isolate was sequenced and its sequence shared about 99.8% similarity with the N. flavescens standard strains, but about 20.8% similarity with the H. pylori. Further study of antibiotics-resistance revealed the N. flavescens isolate is high resistant to metronidazole, but highly sensitive to ampicillin sodium. To summarize, a urease-expressing N. flavescens strain was isolated and identified from Chinese gastritis patients; the encouraging results provides an important reference for the further study of its pathogenicity and the reasonable diagnosis and use of antibiotics clinically.
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Gastrite/diagnóstico , Gastrite/microbiologia , Neisseria/isolamento & purificação , Infecções por Neisseriaceae/diagnóstico , Infecções por Neisseriaceae/microbiologia , Urease/análise , Biópsia , Análise por Conglomerados , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Humanos , Testes de Sensibilidade Microbiana , Neisseria/efeitos dos fármacos , Neisseria/enzimologia , Neisseria/genética , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNARESUMO
The paper introduces a training system for foot ulcer patients based on three axis accelerometer, which uses three axis accelerometer and Apple mobile phone platform to guide foot ulcer patients to carry out a variety of lower limb muscle tissues training. The acceleration values of three directions for the foot training is obtained by analog-to-digital conversion and transmitted to the Apple mobile phone via its Bluetooth low energy. The Apple mobile phone accomplishes acceleration data preprocessing, numerical filtering and adaptive dual-threshold processing by our developed application program, so as to achieve the purpose of foot gesture recognition. The experimental result shows that the design can effectively present the training situation and effect of patients, encourage patients to adhere to the training, and provide some reference data for doctors and patients.
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BACKGROUND: Acute-on-chronic liver failure (ACLF) is a major cause of hepatic death in the world, but no population-based studies have evaluated the incidence of ACLF. This study was conducted to determine the incidence and short-term outcomes of ACLF in a region of Eastern China. METHODS: In this prospective cross-sectional study, we collected data from public hospitals in Nantong city between January 1, 2005, and December 31, 2014. All hospitals with admission potential for ACLF patients were included. The primary outcome was ACLF defined as severe jaundice and coagulopathy with underlying chronic liver disease, according to diagnostic and laboratory criteria suggested by Chinese Society for Hepatology (CSH). RESULTS: During the 10-year period, a consecutive sample of 1934 ACLF patients was included in this study. The overall ACLF incidence rate over the 10-year period was 2.53 (95% confidence interval, 2.16-2.91) per 100,000 population per year, decreasing from 3.35 in 2005 to 2.06 in 2014. Chronic hepatitis B virus (HBV) infection was the leading cause of chronic liver disease and HBV reactivation was the most common cause of acute hepatic event. The 28-day mortality for the ACLF patients had a clear decline during the study period, form 50.39% in 2005 to 35.44% in 2014. CONCLUSIONS: In the Eastern China population, the incidence of ACLF is decreasing and the prognosis improving. Short-term mortality was associated with the presence of cirrhosis and growing age. While ACLF remains a life-threatening disorder, our findings suggest that nationwide and long-term cohorts should be conducted for the natural history of ACLF.
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Insuficiência Hepática Crônica Agudizada/epidemiologia , Hepatite B Crônica/complicações , Cirrose Hepática/epidemiologia , Insuficiência Hepática Crônica Agudizada/etiologia , Insuficiência Hepática Crônica Agudizada/mortalidade , Adolescente , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China/epidemiologia , Estudos Transversais , Feminino , Hepatite B Crônica/epidemiologia , Humanos , Incidência , Cirrose Hepática/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Adulto JovemRESUMO
PURPOSE: To investigate the correlation between the preoperative biometric parameters of the anterior segment and the vault after implantable Collamer lens (ICL) implantation via this retrospective study. DESIGN: Retrospective clinical study. METHODS: A total of 78 eyes from 41 patients who underwent ICL implantation surgery were included in this study. Preoperative biometric parameters, including white-to-white (WTW) diameter, central corneal thickness, keratometer, pupil diameter, anterior chamber depth, sulcus-to-sulcus diameter, anterior chamber area (ACA) and central curvature radius of the anterior surface of the lens (Lenscur), were measured. Lenscur and ACA were measured with Rhinoceros 5.0 software on the image scanned with ultrasound biomicroscopy (UBM). The vault was assessed by UBM 3 months after surgery. Multiple stepwise regression analysis was employed to identify the variables that were correlated with the vault. RESULTS: The results showed that the vault was correlated with 3 variables: ACA (22.4 ± 4.25 mm2), WTW (11.36 ± 0.29 mm) and Lenscur (9.15 ± 1.21 mm). The regressive equation was: vault (mm) = 1.785 + 0.017 × ACA + 0.051 × Lenscur - 0.203 × WTW. CONCLUSIONS: Biometric parameters of the anterior segment (ACA, WTW and Lenscur) can predict the vault after ICL implantation using a new regression equation.
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Câmara Anterior/diagnóstico por imagem , Lentes Intraoculares , Miopia/cirurgia , Refração Ocular/fisiologia , Adulto , Feminino , Seguimentos , Humanos , Masculino , Microscopia Acústica , Pessoa de Meia-Idade , Miopia/diagnóstico , Miopia/fisiopatologia , Período Pré-Operatório , Prognóstico , Estudos Retrospectivos , Acuidade Visual , Adulto JovemRESUMO
Objective: To investigate the resistance of E77.43 gene of Microtus fortisï¼MfE77.43ï¼ to Schistosoma japonicum infection. Methods: MfE77.43 was constructed into the recombinant Adeno-associated virus AAV2. The AAV2-MfE77.43 was transfected into HEK293 cells by the calcium phosphate DNA coprecipitation method. The recombinant rAAV2-MfE77.43 was purified and total RNA was extracted from the transfected cells. The expression of E77.43 was examined by RT-PCR and the purity of rAAV2-MfE77.43 was analyzed by SDS-PAGE. Eighteen KM mice were divided into three groups ï¼n=6 in each groupï¼. Mice in the experiment group were intramuscularly injected on days 0, 3 and 7 with 400 µl recombinant AAV2-MfE77.43 virus which was 5-fold diluted in normal saline. Mice in negative control and blank control groups received same volume of pAAV or normal saline. Venous blood was collected through the tail before each injection, and E77.43 expression in plasma was detected by dot-ELISA method. After the last injection, each mouse was infected with 40 S. japonicum cercariae and sacrificed on day 41 after infection. Adult worms and liver eggs per gramï¼LEPGï¼ were counted. Worm and egg reduction rate was calculated respectively. Egg granulomas were observed by HE staining. Results: RT-PCR resulted in a 330 bp specific band. SDS-PAGE of virus shell protein revealed three protein bands with M(r) of 87 000, 72 000 and 62 000, respectively. Dot-ELISA showed that E77.43 protein began to be expressed on day 3 after rAAV2-MfE77.43 injection, remaining stable till day 41. The adult worm number and LEPG were 20.16±3.93 and 19 800±2 715, respectively, with a worm and egg reduction rate of 27.3% and 26.2% in the experiment group. While the worm number and LEPG in the negative control group were 29.16±2.44 and 28 000±2 192ï¼P<0.01ï¼, respectively. HE staining and observation revealed fewer eosinophils and inflammatory cells around the liver eggs in the therapy group. Conclusion: The E77.43 gene shows protective effects against S. japonicum infection, indicating that E77.43 may participate in the natural resistance of Microtus fortis to S. japonicum infection.
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Schistosoma japonicum , Esquistossomose Japônica , Animais , Arvicolinae , Cercárias , Granuloma , Células HEK293 , Humanos , Fígado , Camundongos , Camundongos Endogâmicos BALB CRESUMO
In this study, two polymorphs of the [1,1'-dibutyl-4,4'-bipyridinium][Ni(mnt)2] salt (1) were synthesized. The dark-green polymorph (designated as 1-g) was prepared under ambient conditions by the rapid precipitation method in aqueous solutions. Subsequently, the red polymorph (labeled as 1-r) was obtained by subjecting 1-g to ultrasonication in MeOH at room temperature. Microanalysis, infrared spectroscopy, thermogravimetry (TG), differential scanning calorimetry (DSC), and powder X-ray diffraction (PXRD) techniques were used to characterize the two polymorphs. Both 1-g and 1-r exhibit structural phase transitions: a reversible phase transition at â¼403 K (â¼268 K) upon heating and 384 K (â¼252 K) upon cooling for 1-g (1-r) within the temperature range below 473 K. Interestingly, on heating 1-r to 523 K, an irreversible phase transition occurred at about 494 K, resulting in the conversion of 1-r into 1-g. Relative to 1-r, 1-g represents a thermodynamically metastable phase wherein numerous high-energy conformations in butyl chains of cations are confined within the lattice owing to quick precipitation or rapid annealing from higher temperatures. Through variable-temperature single crystal and powder X-ray diffractions, UV-visible spectroscopy, dielectric spectroscopy, and DSC analyses, this study delves into the mechanism underlying phase transitions for each polymorph and the manual transformation between 1-g and 1-r as well.
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Pest management technology has been a promising bioconversion method for waste resource utilization. Unlike many pests that consume waste, the larvae of Lucilia sericata, also known as maggots, have many outstanding advantages as following: with their strong adaption to environment and not easily infected and exhibiting a medicinal nutritional value. Herein, the potential efficacies of maggot polysaccharides (MP), as well as their underlying mechanisms, were explored in Dextran sulfate sodium (DSS)-induced colitis mice and TNF-α-elicited Caco-2 cells. We extracted two bioactive polysaccharides from maggots, MP-80 and MP-L, whose molecular weights were 4.25 × 103 and 2.28 × 103 g/mol, respectively. MP-80 and MP-L contained nine sugar residues: 1,4-α-Arap, 1,3-ß-Galp, 1,4,6-ß-Galp, 1,6-α-Glcp, 1-α-Glcp, 1,4-ß-Glcp, 1-ß-Xylp, 1,2-α-Manp, and 1-ß-Manp. We demonstrated that MP-80 and MP-L significantly ameliorated DSS-induced symptoms and histopathological damage. Immuno-analysis revealed that compared with MP-L, MP-80 could better restore intestinal barrier and reduced inflammation by suppressing NLRP3/NF-κB pathways, which might be attributed to its enriched galactose fraction. Moreover, 16S rRNA sequencing revealed that MP-80 and MP-L both improved the dysbiosis and diversity of gut microbiota and acted on multiple microbial functions. Our study sheds new light on the possibility of using maggot polysaccharides as an alternative therapy for colitis.
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Colite Ulcerativa , Sulfato de Dextrana , Microbioma Gastrointestinal , Larva , Polissacarídeos , Animais , Microbioma Gastrointestinal/efeitos dos fármacos , Larva/efeitos dos fármacos , Polissacarídeos/farmacologia , Polissacarídeos/química , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Humanos , Camundongos , Células CACO-2 , Dípteros/química , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Modelos Animais de Doenças , MasculinoRESUMO
OBJECTIVE: To evaluate the analgesic effects of total flavonoids of Longxuejie (Resina Dracaenae Cochinchinensis) (TFDB) and explore the possible analgesic mechanism associated with transient receptor potential vanilloid 1 (TRPV1). METHODS: Whole-cell patch clamp technique was used to observe the effects of TFDB on capsaicin-induced TRPV1 currents. Rat experiments in vivo were used to observe the analgesic effects of TFDB. Western blot and immunofluorescence experiments were used to test the change of TRPV1 expression in DRG neurons induced by TFDB. RESULTS: Results showed that TFDB inhibited capsaicin-induced TRPV1 receptor currents in acutely isolated dorsal root ganglion (DRG) neurons of rats and the half inhibitory concentration was (16.7 ± 1.6) mg/L. TFDB (2-20 mg/kg) showed analgesic activity in the phase â ¡ of formalin test and (0.02-2 mg per paw) reduced capsaicin-induced licking times of rats. TFDB (20 mg/kg) was fully efficacious on complete Freund's adjuvant (CFA)-induced inflammatory thermal hyperalgesia and capsaicin could weaken the analgesic effects. The level of TRPV1 expressions of DRG neurons was also decreased in TFDB-treated CFA-inflammatory pain rats. CONCLUSION: All these results indicated that the analgesic effect of TFDB may contribute to their modulations on both function and expression of TRPV1 channels in DRG neurons.
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Analgésicos , Flavonoides , Gânglios Espinais , Canais de Cátion TRPV , Animais , Ratos , Analgésicos/farmacologia , Analgésicos/química , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Flavonoides/farmacologia , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Gânglios Espinais/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Dor/tratamento farmacológico , Dor/metabolismo , Ratos Sprague-Dawley , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismoRESUMO
In the present study, a comprehensive strategy integrating affinity ultrafiltration high-performance liquid chromatography quadrupole-time-of-flight mass spectrometry (UF-HPLC-Q-TOF-MS), in silico molecular docking and bioassays was established to rapidly screen natural SOD activators from traditional Chinese medicines. As illustrative case studies, Schisandra chinensis, Fructus cnidii and Radix ophiopogonis were chosen to develop and verify the strategy. The HPLC-Q-TOF-MS was used to identify the compounds in comparison with reference standards and literature data. A total of eight compounds, including four biphenyl-cyclooctene ligands from Schisandra chinensis and four coumarins from Fructus cnidii, were found to potentially increase SOD activities. No ligands were found in the extract of Radix ophiopogonis. Then, in silico molecular docking was performed to investigate the binding site and binding affinity of the candidates on SOD. Compared to the nonspecific ligands screened from the extract, the specific ligands presented stronger binding affinities. In addition, the activity and kinetic parameters of the SOD-ligand were investigated through an improved pyrogallol autoxidation method. Gomisin J and xanthotoxin showed a stronger ability to increase SOD activities. The present study indicated that combining UF-HPLC-Q-TOF-MS and in silico molecular docking offers a powerful and meaningful tool to rapidly screen SOD activators from traditional Chinese medicines.
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Medicamentos de Ervas Chinesas , Simulação de Acoplamento Molecular , Medicamentos de Ervas Chinesas/química , Ultrafiltração/métodos , Cromatografia Líquida de Alta Pressão/métodos , Superóxido DismutaseRESUMO
MicroRNAs (miRNAs) are important biomacromolecules used as biomarkers for the diagnosis of several diseases. However, current detection strategies are limited by expensive equipment and complicated procedures. Here, we develop a portable, sensitive, and stable (Eu-MOF)-based sensing platform to detect miRNA via smartphone. The Eu-MOF absorbs the carboxyfluorescein (FAM)-tagged probe DNA (pDNA) to generate hybrid pDNA@Eu-MOF, which can efficiently quench the fluorescence of FAM through a photoinduced electron transfer (PET) process. When integrated with a smartphone, the nonemissive pDNA@ Eu-MOF hybrid could be utilized as a portable and sensitive platform to sense miRNA (miR-892b) with a detection limit of 0.32 pM, which could be even distinguished by the naked eye. Moreover, this system demonstrates high selectivity for identifying miRNA family members with single-base mismatches. Furthermore, the expression levels of miRNA in cancer cell samples could be analyzed accurately. Therefore, the proposed method offers a promising guideline for the design of MOF-based sensing strategies and expands their potential applications for diagnostic purposes.
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Estruturas Metalorgânicas , MicroRNAs , MicroRNAs/genética , Luminescência , Sondas de DNA/genética , Fluorescência , Limite de DetecçãoRESUMO
A thermochromic or mechanochromic material can switch between at least two stable states in response to changes in temperature or static pressure/strain. In this study, we investigated a Ni-dithiolene dianion salt, 1,1'-diheptyl-4,4'-bipyridinium bis(maleonitriledithiolato)nickelate (1), and found that its cations and anions stack alternately to form a uniform mixed stack. These mixed stacks then combine to form a molecular solid through Coulomb and van der Waals interactions. Upon heating, 1 undergoes a reversible phase transition at around 340/320 K during the first heating/cooling cycle, resulting in rapid thermochromism with a color change from green (stable state) to red (metastable state) within a few seconds. This is the first report of a crystal of bis(maleonitriledithiolato)nickelate(II) salt with green color. Additionally, 1 exhibits irreversible mechanochromism, intense near-IR absorbance, and a dielectric anomaly. The structural phase transition is responsible for these properties, as it induces alterations in the π-orbital overlap between the anion and cation within a mixed stack. The intense near-IR absorbance arises from the ion-pair charge transfer transition from [Ni(mnt)2]2- to 4,4'-bipyridinium.
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Objective: We determined the distribution of constitutional types of high-normal blood pressure in Traditional Chinese Medicine (TCM) and provided evidence for the prevention of high-normal blood pressure and hypertension. Methods: Eight digital databases were searched from January 2011 to November 2022, including PubMed, EMBASE, Web of Science, EBSCOhost, CNKI, CBM, Wangfang, and CQVIP. We performed a meta-analysis with the random-effects model or fixed-effects model to describe the distribution of constitutional types of high-normal blood pressure in TCM. The studies were assessed based on heterogeneity testing and the potential for publication bias. The meta-analysis was performed on Stata software 15.0. Results: A total of 17 studies with 8118 participants were included in this meta-analysis. The proportion of the biased constitution (82.3%; 95% CI: 75.6%-89.1%, p < 0.001) was higher than the balanced constitution (17.3%; 95% CI: 10.7-23.8%, p < 0.001). Phlegm-dampness constitution, Yin-deficiency constitution, and damp-heat constitution accounted for 16.0% (95%CI: 10.5-21.5%, p < 0.001), 14.8% (95% CI: 11.0-18.6%, p < 0.001), 11.3% (95% CI: 8.0-14.5%, p < 0.001) of the total high-normal blood pressure cases, respectively. The subgroup analyses performed that region, age and gender were positively associated with the distribution of constitution types of high-normal blood pressure in TCM. Compared with the general population, the risk of high-normal blood pressure in people with the phlegm-dampness constitution, Yin-deficiency constitution, and blood-stasis constitution was 2.665 (95%CI: 2.286-3.106, p < 0.001), 2.378 (95%CI: 1.197-4.724, p = 0.013), 1.965 (95%CI: 1.634-2.363, p < 0.001) times of the general population, respectively. Meanwhile, the risk of high-normal blood pressure was lower in people with a balanced constitution (0.248, 95%CI: 0.165-0.372, p < 0.001). Conclusions: Phlegm-dampness constitution, Yin-deficiency constitution, and damp-heat constitution were the common constitution types of high-normal blood pressure. There might also be differences in the distribution characteristics of TCM constitution among people with high-normal blood pressure in different regions, ages, and genders. Finally, a balanced constitution might be a protective factor for hypertensive people.
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Depression can trigger an inflammatory response that affects the immune system, leading to the development of other diseases related to inflammation. Xiao-Yao-San (XYS) is a commonly used formula in clinical practice for treating depression. However, it remains unclear whether XYS has a modulating effect on the inflammatory response associated with depression. The objective of this study was to examine the role and mechanism of XYS in regulating the anti-inflammatory response in depression. A chronic unpredictable mild stress (CUMS) mouse model was established to evaluate the antidepressant inflammatory effects of XYS. Metabolomic assays and network pharmacology were utilized to analyze the pathways and targets associated with XYS in its antidepressant inflammatory effects. In addition, molecular docking, immunohistochemistry, Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR), and Western Blot were performed to verify the expression of relevant core targets. The results showed that XYS significantly improved depressive behavior and attenuated the inflammatory response in CUMS mice. Metabolomic analysis revealed the reversible modulation of 21 differential metabolites by XYS in treating depression-related inflammation. Through the combination of liquid chromatography and network pharmacology, we identified seven active ingredients and seven key genes. Furthermore, integrating the predictions from network pharmacology and the findings from metabolomic analysis, Vascular Endothelial Growth Factor A (VEGFA) and Peroxisome Proliferator-Activated Receptor-γ (PPARG) were identified as the core targets. Molecular docking and related molecular experiments confirmed these results. The present study employed metabolomics and network pharmacology analyses to provide evidence that XYS has the ability to alleviate the inflammatory response in depression through the modulation of multiple metabolic pathways and targets.
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Some natural products are important sources of treatments for hypertension based on their potential inhibitory effects on angiotensin-converting enzyme (ACE); however, it is difficult to identify natural ACE inhibitors (ACEIs) due to the complex secondary metabolite environment of natural products. Enzyme immobilization is an important method for screening active constituents in natural products, but this method can sometimes return false-positive and false-negative results. To improve the accuracy and reliability of ligand-fishing methods, we established a novel strategy based on enzyme-immobilized ligand fishing combined with active-site blocking and directional enrichment technologies. We first synthesized ACE-immobilized mesoporous magnetic beads and then verified the screened compounds by molecular docking and in vitro activity detection. We then used active-site blocking to exclude non-specific binding constituents and applied directional enrichment to enrich the low-content constituents for ligand fishing. The screening identified six potential ACEIs from Scutellariae Radix and eight potential ACEIs from Lonicerae japonicae flos, and their inhibitory activity was confirmed by molecular docking simulations and in vitro activity detection. This process screened six additional compounds and excluded two false-positive results as compared with results exclusively using enzyme immobilization. This strategy provides a feasible method for screening active compounds in natural products.