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BACKGROUND: A comprehensive overview of artificial intelligence (AI) for cardiovascular disease (CVD) prediction and a screening tool of AI models (AI-Ms) for independent external validation are lacking. This systematic review aims to identify, describe, and appraise AI-Ms of CVD prediction in the general and special populations and develop a new independent validation score (IVS) for AI-Ms replicability evaluation. METHODS: PubMed, Web of Science, Embase, and IEEE library were searched up to July 2021. Data extraction and analysis were performed for the populations, distribution, predictors, algorithms, etc. The risk of bias was evaluated with the prediction risk of bias assessment tool (PROBAST). Subsequently, we designed IVS for model replicability evaluation with five steps in five items, including transparency of algorithms, performance of models, feasibility of reproduction, risk of reproduction, and clinical implication, respectively. The review is registered in PROSPERO (No. CRD42021271789). RESULTS: In 20,887 screened references, 79 articles (82.5% in 2017-2021) were included, which contained 114 datasets (67 in Europe and North America, but 0 in Africa). We identified 486 AI-Ms, of which the majority were in development (n = 380), but none of them had undergone independent external validation. A total of 66 idiographic algorithms were found; however, 36.4% were used only once and only 39.4% over three times. A large number of different predictors (range 5-52,000, median 21) and large-span sample size (range 80-3,660,000, median 4466) were observed. All models were at high risk of bias according to PROBAST, primarily due to the incorrect use of statistical methods. IVS analysis confirmed only 10 models as "recommended"; however, 281 and 187 were "not recommended" and "warning," respectively. CONCLUSION: AI has led the digital revolution in the field of CVD prediction, but is still in the early stage of development as the defects of research design, report, and evaluation systems. The IVS we developed may contribute to independent external validation and the development of this field.
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Inteligência Artificial , Doenças Cardiovasculares , Humanos , Doenças Cardiovasculares/diagnóstico , Medição de Risco/métodos , Programas de Rastreamento/métodos , Reprodutibilidade dos TestesRESUMO
Epimedii Folium (EF) is a botanical dietary supplement to benefit immunity. Baohuoside I (BI), a prenylated flavonoid derived from EF, has exhibited the cholestatic risk before. Here, the mechanism of BI on the stability and membrane localization of liver MRP2, a bile acid exporter in the canalicular membrane of hepatocytes, was investigated. The fluorescent substrate of MRP2, CMFDA was accumulated in sandwich-cultured primary mouse hepatocytes (SCH) under BI stimulation, followed by reduced membrane MRP2 expression. BI triggered MRP2 endocytosis associated with oxidative stress via inhibition of the NRF2 signaling pathway. Meanwhile, BI promoted the degradation of MRP2 by reducing its SUMOylation and enhancing its ubiquitination level. Co-IP and fluorescence colocalization experiments all proved that MRP2 was a substrate protein for SUMOylation for SUMO proteins. CHX assays showed that SUMO1 prolonged the half-life of MRP2 and further increased its membrane expression, which could be reversed by UBC9 knockdown. Correspondingly, MRP2 accumulated in the cytoplasm by GP78 knockdown or under MG132 treatment. Additionally, the SUMOylation sites of MRP2 were predicted by the algorithm, and a conversion of lysines to arginines at positions 940 and 953 of human MRP2 caused its decreased stability and membrane location. K940 was further identified as the essential ubiquitination site for MRP2 by an in vitro ubiquitination assay. Moreover, the decreased ubiquitination of MRP2 enhanced the SUMOylation MRP2 and vice versa, and the crosstalk of these two modifiers could be disrupted by BI. Collectively, our findings indicated the process of MRP2 turnover from the membrane to cytoplasm at the post-translational level and further elucidated the novel toxicological mechanism of BI.
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Proteínas Associadas à Resistência a Múltiplos Medicamentos , Sumoilação , Camundongos , Animais , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Proteína 2 Associada à Farmacorresistência Múltipla , Hepatócitos/metabolismo , Flavonoides/metabolismo , UbiquitinaçãoRESUMO
With the increasing use of oral contraceptives and estrogen replacement therapy, the incidence of estrogen-induced cholestasis (EC) has tended to rise. Psoralen (P) and isopsoralen (IP) are the major bioactive components in Psoraleae Fructus, and their estrogen-like activities have already been recognized. Recent studies have also reported that ERK1/2 plays a critical role in EC in mice. This study aimed to investigate whether P and IP induce EC and reveal specific mechanisms. It was found that P and IP increased the expression of esr1, cyp19a1b and the levels of E2 and VTG at 80 µM in zebrafish larvae. Exemestane (Exe), an aromatase antagonist, blocked estrogen-like activities of P and IP. At the same time, P and IP induced cholestatic hepatotoxicity in zebrafish larvae with increasing liver fluorescence areas and bile flow inhibition rates. Further mechanistic analysis revealed that P and IP significantly decreased the expression of bile acids (BAs) synthesis genes cyp7a1 and cyp8b1, BAs transport genes abcb11b and slc10a1, and BAs receptor genes nr1h4 and nr0b2a. In addition, P and IP caused EC by increasing the level of phosphorylation of ERK1/2. The ERK1/2 antagonists GDC0994 and Exe both showed significant rescue effects in terms of cholestatic liver injury. In conclusion, we comprehensively studied the specific mechanisms of P- and IP-induced EC and speculated that ERK1/2 may represent an important therapeutic target for EC induced by phytoestrogens.
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Colestase , Ficusina , Furocumarinas , Psoralea , Animais , Produtos Biológicos/farmacologia , Produtos Biológicos/química , Colestase/induzido quimicamente , Colestase/metabolismo , Estrogênios/metabolismo , Estrogênios/farmacologia , Ficusina/farmacologia , Furocumarinas/farmacologia , Furocumarinas/química , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Psoralea/química , Peixe-ZebraRESUMO
The saponin-enriched extract from Celosiae Semen is a promising resource owing to its lipid-lowering activity. However, triterpenoid saponins are difficult to extract owing to their high molecular weight and strong water solubility. The aim of this paper was to explore an eco-friendly and effective technology of extraction and enrichment of total triterpenoid saponins to obtain high lipid-lowering fractions. Initially, Box-Behnken design experiments were employed to optimize the heat reflux extraction process on the basic of mono-factor experiments. Afterwards, the crude extract was further purified using D-101 resin, and the purification parameters were investigated based on adsorption/desorption experiments and biological activity assay. Under optimal conditions, the purity of the finally obtained total triterpenoid saponins was increased by 7.28-fold. The lipid-lowering activities of the six main triterpenoid saponins were evaluated in HepG2 cells induced by palmitic acid. The results of Oil Red O staining showed that the compounds all exhibited potential lipid-lowering activity. The structure-activity relationship analysis suggested that the oligosaccharide chain at C-28 played an essential role in their lipid-lowering activity and the substituent group at C-23 site also showed important effects. The optimal extraction and purification methods may facilitate the utilization of Celosiae Semen for the industrial production as a functional food and drug.
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Amaranthaceae , Metabolismo dos Lipídeos , Saponinas/química , Saponinas/farmacologia , Triterpenos/química , Amaranthaceae/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Humanos , Células Hep G2 , Etanol/químicaRESUMO
In recent years, there has been explosive development in artificial intelligence (AI), which has been widely applied in the health care field. As a typical AI technology, machine learning models have emerged with great potential in predicting cardiovascular diseases by leveraging large amounts of medical data for training and optimization, which are expected to play a crucial role in reducing the incidence and mortality rates of cardiovascular diseases. Although the field has become a research hot spot, there are still many pitfalls that researchers need to pay close attention to. These pitfalls may affect the predictive performance, credibility, reliability, and reproducibility of the studied models, ultimately reducing the value of the research and affecting the prospects for clinical application. Therefore, identifying and avoiding these pitfalls is a crucial task before implementing the research. However, there is currently a lack of a comprehensive summary on this topic. This viewpoint aims to analyze the existing problems in terms of data quality, data set characteristics, model design, and statistical methods, as well as clinical implications, and provide possible solutions to these problems, such as gathering objective data, improving training, repeating measurements, increasing sample size, preventing overfitting using statistical methods, using specific AI algorithms to address targeted issues, standardizing outcomes and evaluation criteria, and enhancing fairness and replicability, with the goal of offering reference and assistance to researchers, algorithm developers, policy makers, and clinical practitioners.
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Doenças Cardiovasculares , Aprendizado de Máquina , Humanos , Reprodutibilidade dos Testes , AlgoritmosRESUMO
BACKGROUND: Internet hospitals (IHs) have rapidly developed as a promising strategy to address supply-demand imbalances in China's medical industry, with their capabilities directly dependent on information platform functionality. Moreover, a novel theory of "Trinity" smart hospital has provided advanced guidelines of IHs construction. OBJECTIVE: To explore the construction experience, construction models, and development prospects based on operational data from IHs. METHODS: Based on existing information systems and internet service functionalities, our hospital has built a "Smart Hospital Internet Information Platform (SHIIP)" for IHs operation, actively to expand online services, digitalize traditional healthcare, and explore healthcare services modes throughout the entire process and lifecycle. This article encompasses the platform architecture design, technological applications, patient service content and processes, healthcare professional support features, administrative management tools, and associated operational data. RESULTS: Our platform has presented a remarkable set of data, including 82,279,669 visits, 420,120 online medical consultations, 124,422 electronic prescriptions, 92,285 medication deliveries, 6,965,566 pre-diagnosis triages, 4,995,824 offline outpatient appointments, 2,025 medical education articles with a total of 15,148,310 views, and so on. These data demonstrate the significant role of IH as an indispensable component of our physical hospital services, with a deep integration between online and offline healthcare systems. CONCLUSIONS: Attributing to extreme convenience and improved efficiency, our IH has achieved a wide recognition and use from both the public and healthcare workers, and the upward trends in multiple data metrics suggest a promising outlook for its sustained and positive development in the future. Our pioneering exploration holds tremendous significance and serves as a valuable guiding reference for IHs construction and the progressive development of the internet healthcare sector.
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Epimedii folium (EF) is an effective herbal medicine in osteoporosis treatment, but the clinical utilization of EF has been limited due to potential hepatotoxicity. The previous studies identified that baohuoside I (BI), the main active component of EF, was relevant to EF-induced liver injury. However, the mechanisms of BI causing direct injury to hepatocytes remain unclear. Here, we reveal that BI inhibits FXR-mediated signaling pathway via targeting estrogen receptor α (ER α), leading to the accumulation of bile acids (BAs). Targeted bile acid analyses show BI alters the BA composition and distribution, resulting in impaired BA homeostasis. Mechanistically, BI induces FXR-dependent hepatotoxicity at transcriptional level. Additionally, ER α is predicted to bind to the FXR promoter region based on transcription factor binding sites databases and we further demonstrate that ER α positively regulates FXR promoter activity and affects the expression of target genes involved in BA metabolism. Importantly, we discover that ER α and its mediated FXR transcription regulation might be involved in BI-induced liver injury via ligand-dependent ER α degradation. Collectively, our findings indicate that FXR is a newly discovered target gene of ER α mediated BI-induced liver injury, and suggest BI may be responsible for EF-induced liver injury.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Receptores Citoplasmáticos e Nucleares , Humanos , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores Citoplasmáticos e Nucleares/farmacologia , Ácidos e Sais Biliares/metabolismo , Ácidos e Sais Biliares/farmacologia , Receptor alfa de Estrogênio/genética , Receptor alfa de Estrogênio/metabolismo , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Fígado , Homeostase , Transdução de SinaisRESUMO
BACKGROUND: Syphilis is a sexually transmitted disease caused by Treponema pallidum, and the infection source is syphilis patients. This study aimed to estimate the incidence, mortality rate, and disability-adjusted life years (DALYs) of syphilis to improve the understanding of the current global situation of syphilis. METHODS: This study collected data on syphilis incidence, mortality, and DALYs from the 2019 Global Burden of Disease database. RESULTS: The global number of incident cases and age-standardized incidence rate (ASIR) increased from 8,845,220 (95% UI: 6,562,510-11,588,860) in 1990 to 14,114,110 (95% UI: 10,648,490-18,415,970) in 2019 and 160.03/100,000 persons (95% UI: 120.66-208.1) to 178.48/100,000 persons (95% UI: 134.94-232.34), respectively. The estimated annual percentage change (EAPC) in the ASIR was 0.16 (95% CI: 0.07-0.26). The EAPC in the ASIR associated with high and high-middle sociodemographic indices increased. The ASIR increased among males but decreased among females, and the incidence peaked among males and females between the ages of 20 and 30 years. The EAPCs in the age-standardized death rate and age-standardized DALY rate decreased. CONCLUSIONS: The incidence and ASIR of syphilis increased worldwide from 1990 to 2019. Only the regions with high and high-middle sociodemographic indices showed an increase in the ASIR. Moreover, the ASIR increased among males but decreased among females. The age-standardized death rate and DALY rate both declined worldwide. The increase in the global ASIR of syphilis is a challenge.
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Carga Global da Doença , Sífilis , Masculino , Feminino , Humanos , Adulto Jovem , Adulto , Anos de Vida Ajustados por Qualidade de Vida , Saúde Global , IncidênciaRESUMO
Dictamnine (DTN), a furoquinoline alkaloid isolated from Dictamni Cortex, is responsible for the liver injury caused by Dictamni Cortex and the preparations. Discovering new biomarkers with high specificity and sensitivity for diagnosis and tracing the source of DTN-induced liver injury is urgently needed. Considering that metabolic activation of DTN has been suggested as a primary trigger initiating hepatotoxicity, the present study aimed to investigate the bio-activation process of DTN in vitro and in mice and to explore whether the adducts could be developed as exposure biomarkers. When trapping with N-acetyl-cysteine (NAC) and glutathione (GSH) in mouse liver microsomes and CYP3A4 overexpressed L02 cells, two isomers of DTN-NAC adducts were detected in both systems and one DTN-GSH adduct was found in mouse liver microsomes. As expected, one DTN-NAC adduct was also found in plasma and bile of mice with liver injury after DTN exposure. Moreover, mouse liver microsomes were used to simulate the conjugation of serum albumin with metabolically activated DTN. The sole modified peptide 25 DAHKSEVAHR34 was found, and the oxidative metabolites of DTN might bind to the side chain amino of albumin at Arg34. The above findings not only provided confirmative evidence that DTN was metabolically activated to induce liver injury but also suggested that the adducts had the potential to be developed as exposure biomarkers of DTN-induced liver injury.
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Doença Hepática Crônica Induzida por Substâncias e Drogas , Camundongos , Animais , Ativação Metabólica , Doença Hepática Crônica Induzida por Substâncias e Drogas/metabolismo , Microssomos Hepáticos/metabolismo , Acetilcisteína , Glutationa/metabolismoRESUMO
Psoralen and isopsoralen are the pharmacologically important but hepatotoxic components in Psoraleae Fructus. The purpose of this study was to reveal the underlying mechanism of psoralen/isopsoralen-induced hepatotoxicity. Initially, we applied integrated analyses of transcriptomic and metabolomic profiles in mice treated with psoralen and isopsoralen, highlighting the xenobiotic metabolism by cytochromes P450 as a potential pathway. Then, with verifications of expression levels by qRT-PCR and western blot, affinities by molecular docking, and metabolic contributions by recombinant human CYP450 and mouse liver microsomes, CYP1A2 was screened out as the key metabolic enzyme. Afterwards, CYP1A2 induction and inhibition models in HepG2 cells and mice were established to verify the role of CYP1A2, demonstrating that induction of CYP1A2 aggravated the hepatotoxicity, and conversely inhibition alleviated the hepatotoxic effects. Additionally, we detected glutathione adducts with reactive intermediates of psoralen and isopsoralen generated by CYP1A2 metabolism in biosystems of recombinant human CYP1A2 and mouse liver microsomes, CYP1A2-overexpressed HepG2 cells, mice livers and the chemical reaction system using UPLC-Q-TOF-MS/MS. Ultimately, the high-content screening presented the cellular oxidative stress and relevant hepatotoxicity due to glutathione depletion by reactive intermediates. In brief, our findings illustrated that CYP1A2-mediated metabolic activation is responsible for the psoralen/isopsoralen-induced hepatotoxicity.
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Doença Hepática Induzida por Substâncias e Drogas , Furocumarinas , Animais , Humanos , Camundongos , Ficusina/toxicidade , Citocromo P-450 CYP1A2 , Ativação Metabólica , Transcriptoma , Espectrometria de Massas em Tandem , Simulação de Acoplamento Molecular , Furocumarinas/toxicidade , Metabolômica , GlutationaRESUMO
BACKGROUND: Diagnostic panels based on multiple biomarkers and clinical characteristics are considered more favorable than individual biomarker to diagnose hepatocellular carcinoma (HCC). Based on age, sex, alpha-fetoprotein (AFP), and protein induced by vitamin K absence II (PIVKA-II) with/without AFP-L3, ASAP and GALAD models are potential diagnostic panels. The diagnostic performances of these two panels were compared relative to HCC detection among patients with various etiologies of chronic liver diseases (CLDs). METHODS: A multicenter case-control study recruited CLDs patients with and without HCC from 14 Chinese hospitals. The etiologies of CLDs included hepatitis B virus (HBV), hepatitis C virus (HCV), alcoholic liver disease (ALD), and nonalcoholic fatty liver disease (NAFLD). Using area under the receiver operating characteristic curve (AUC) values, the diagnostic performances of ASAP and GALAD models were compared to detect HCC among patients with various etiologies of CLDs. RESULTS: Among 248 HCC patients and 722 CLD controls, the ASAP model demonstrated the highest AUC (0.886) to detect HCC at any stage, outperforming the GALAD model (0.853, P = 0.001), as well as any individual biomarker (0.687-0.799, all P < 0.001). In the subgroup analysis of various CLDs etiologies, the ASAP model outperformed the GALAD model to HCC independent of CLDs etiology. In addition, the ASAP model performed better in detecting early-stage (BCLC stage 0/A) HCC versus the GALAD model. CONCLUSIONS: Despite using one less laboratory variable (AFP-L3), the ASAP model demonstrated better diagnostic performance than the GALAD model to detect all-stage HCC among patients with various etiologies of CLDs-related HCC.
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The development of formaldehyde (HCHO) gas sensors with high sensitivity, good selectivity, and fast response at room temperature is an important research topic. The resonant microcantilever, with high sensitivity, easy batch manufacturing, and integration, generates sensing signals based on the relationship between the frequency and the mass addition of the adsorbed molecules and shows good application potential in HCHO detection. Herein, we report two species of MoS2 nanosheets (NSs) with 1T and 2H phases as sensitive materials to construct high-performance HCHO resonant cantilever sensors. The 2H-MoS2 gas sensors show better sensitivity toward HCHO compared to the 1T-MoS2 gas sensor. Specifically, the 2H-MoS2 sensor displayed a high sensitivity (Hz) of 13.6-1 ppm HCHO at room temperature, with high selectivity, low limit of detection (10 ppb), and good humidity resistance. The effect of phase structures on the sensing performance was studied by in situ characterizations, thermodynamic analysis, and density functional theory calculations. The good sensing ability could be attributed to the abundant active sites induced by the surface defects, suitable adsorption strength, and the outstanding thermodynamic performance of the 2H-MoS2. The combination of two-dimensional (2D) nanosheet and microcantilever sensors provides a new direction for developing a high-performance room-temperature gas sensor in the future.
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BACKGROUND AND OBJECTIVE: There is a limited number of studies on the performance assessment of the 2017 AAP/EFP classification and the CDC/AAP case definition among pregnant females. This study evaluated the agreement between these two systems and explored a practical tool for screening maternal periodontal diseases by general dentists. MATERIALS AND METHODS: Totally, 204 systemically healthy females at different phases of pregnancy underwent a full-mouth periodontal examination. Demographic characteristics, lifestyles, and systemic conditions were recorded. Referring to the CDC/AAP definition, the diagnostic performance of the AAP/EFP classification was evaluated by the area under the ROC curve (AUC) and statistical tests (e.g., Youden's index and kappa coefficient). Additionally, a modified scoring system of the FDI Periodontal Diseases Chairside Guide (FDI-CG) was formulated with the addition of pregnancy for testing accordingly. RESULTS: Overall, there were 22.1% of the participants in early phase of pregnancy (7-13 weeks) and 77.9% in late phase (34-36 weeks). The majority of them were below 35 years and non-smokers without gestational diabetes. Notably, 30.9% of subjects presented with Moderate/Severe periodontitis (CDC/AAP), and 35.8% with Stages II-IV periodontitis (AAP/EFP). Referring to the CDC/AAP definition, the AUC, Youden's index, and κ of the AAP/EFP classification were 0.979, 0.890, and 92.9%, respectively. The modified FDI-CG system improved the AUC (0.815), Youden's index (63.0%), and κ (0.544) with reference to the original one. CONCLUSIONS: This study shows that the AAP/EFP classification is in high agreement with the CDC/AAP definition among the pregnant women. The phases of pregnancy-integrated FDI scoring system may serve as a convenient screening tool for maternal periodontal diseases in general dental practice.
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Doenças Periodontais , Periodontite , Centers for Disease Control and Prevention, U.S. , Diagnóstico Bucal , Feminino , Humanos , Doenças Periodontais/diagnóstico , Periodontite/diagnóstico , Gravidez , Gestantes , Estados UnidosRESUMO
Liver injury induced by Polygonum multiflorum root (PMR) is an immediate issue requiring global attention. UDP-glucuronosyltransferase 1A1 (UGT1A1) inhibitors are suspected to additively contribute to the hepatotoxicity of PMR. This study was deliberately designed to simultaneously screen UGT1A1 inhibitors from PMR, and their co-contribution to hepatotoxicity was determined. Using ultrafiltration coupled to LC-MS method, four compounds, namely cis-2,3,5,4'-tetrahydroxystilbene-2-O-ß-glucoside, trans-2,3,5,4'-tetrahydroxystilbene-2-O-ß-d-glucoside, emodin-8-O-ß-d-glucoside, and emodin, were screened, exhibiting the in vitro inhibitory activities against UGT1A1 with IC50 values of 76.23, 18.70, 62.18, and 34.02 µM, respectively. The varying activities of the screened UGT1A1 inhibitors were demonstrated by performing a molecular docking simulation. Finally, zebrafish larvae and mice assays demonstrated that the UGT1A1 inhibitors co-contributed to the hepatotoxicity of PMR. These findings are conducive to understand the role of UGT1A1 inhibitors in PMR-induced hepatotoxicity.
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Fallopia multiflora , Animais , Cromatografia Líquida , Camundongos , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Ultrafiltração , Peixe-ZebraRESUMO
The traditional self-supported piezoelectric thin films prepared by filtration methods are limited in practical applications due to their poor tensile properties. The strategy of using flexible polyethylene terephthalate (PET) fabric as the flexible substrate is beneficial to enhancing the flexibility and stretchability of the flexible device, thus extending the applications of pressure sensors. In this work, a novel wearable pressure sensor is prepared, of which uniform and dense ZnO nanoarray-coated PET fabrics are covered by a two-dimensional MXene nanosheet. The ternary structure incorporates the advantages of the three components including the superior piezoelectric properties of ZnO nanorod arrays, the excellent flexibility of the PET substrate, and the outstanding conductivity of MXene, resulting in a novel wearable sensor with excellent pressure-sensitive properties. The PET/ZnO@MXene pressure sensor exhibits excellent sensing performance (S = 53.22 kPa-1), fast response/recovery speeds (150 ms and 100 ms), and superior flexural stability (over 30 cycles at 5% strain). The composite fabric also shows high sensitivity in both motion monitoring and physiological signal detection (e.g., device bending, elbow bending, finger bending, wrist pulse peaks, and sound signal discrimination). These findings provide insight into composite fabric-based pressure-sensitive materials, demonstrating the great significance and promising prospects in the field of flexible pressure sensing.
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Polietilenotereftalatos , Óxido de Zinco , Têxteis , Fenômenos FísicosRESUMO
BACKGROUND: Patients with coronavirus disease 2019 (COVID-19) experience a wide clinical spectrum, with over 2% developing fatal outcome. The prognostic factors for fatal outcome remain sparsely investigated. METHODS: A retrospective cohort study was performed in a cohort of patients with confirmed COVID-19 in one designated hospital in Wuhan, China, from 17 January-5 March 2020. The laboratory parameters and a panel of cytokines were consecutively evaluated until patients' discharge or death. The laboratory features that could be used to predict fatal outcome were identified. RESULTS: Consecutively collected data on 55 laboratory parameters and cytokines from 642 patients with COVID-19 were profiled along the entire disease course, based on which 3 clinical stages (acute stage, days 1-9; critical stage, days 10-15; and convalescence stage, day 15 to observation end) were determined. Laboratory findings based on 75 deceased and 357 discharged patients revealed that, at the acute stage, fatality could be predicted by older age and abnormal lactate dehydrogenase (LDH), urea, lymphocyte count, and procalcitonin (PCT) level. At the critical stage, the fatal outcome could be predicted by age and abnormal PCT, LDH, cholinesterase, lymphocyte count, and monocyte percentage. Interleukin 6 (IL-6) was remarkably elevated, with fatal cases having a more robust production than discharged cases across the whole observation period. LDH, PCT, lymphocytes, and IL-6 were considered highly important prognostic factors for COVID-19-related death. CONCLUSIONS: The identification of predictors that were routinely tested might allow early identification of patients at high risk of death for early aggressive intervention.
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COVID-19 , SARS-CoV-2 , Idoso , COVID-19/mortalidade , China/epidemiologia , Humanos , Laboratórios , Prognóstico , Estudos RetrospectivosRESUMO
INTRODUCTION: Dispensing granule, an innovative product of traditional Chinese medicine decoction, is widely practiced in clinic. As a prerequisite to support the clinical medication, quality consistency between dispensing granule and traditional decoction need to be evaluated. Furthermore, a generally applicable strategy for consistency evaluation of dispensing granule is needed. OBJECTIVE: In this study, we aimed to propose an integrated quality-based strategy to assess consistency between dispensing granule and traditional decoction taking Coptidis Rhizoma (CR) as a case study. METHODOLOGY: For chemical consistency evaluation, efficacy-related Coptis alkaloids were quantified with high-performance liquid chromatography (HPLC). The "Mean ± 3SD" of analyte contents in traditional decoction was considered as the criterion of consistency. And, as auxiliary analysis, principal component analysis (PCA) was employed for data visualisation. For biological consistency evaluation, two one-side t-tests and 90% confidence intervals of the geometric mean ratio of antibacterial zone diameter and 50% inhibitory concentration (IC50 ) of α-glucosidase inhibition were calculated. The scope of 80.00% to 125.00% was taken as in vitro bioequivalence interval. It was considered internally consistent with traditional decoction when the chemical and biological indices of dispensing granule fulfilled the preset criteria simultaneously. RESULTS: Eight out of 20 batches of CR dispensing granule were demonstrated consistent with traditional decoction in chemistry and biological activities. CONCLUSIONS: A generally applicable strategy was recommended that integrates chemical and biological characteristics for consistency evaluation of dispensing granule.
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Coptis , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão , Medicina Tradicional Chinesa , RizomaRESUMO
OBJECTIVE: To analyze the prevalence of diabetes mellitus among middle-aged and older rural adults of Xinxiang county, Henan Province and its correlation with dietary patterns. METHODS: The study was done based on the data collected from a cross-sectional survey of Xinxiang County, which was part of the Prospective Cohort Study on the Common Chronic Non-Communicable Diseases in Rural areas of Henan Province. Randomized cluster sampling was used to select adult respondents (≥18 years old) from among the residents of 17 villages in Xinxiang county. The respondents completed questionnaires, and underwent physical examinations and laboratory tests between April, 2017 and June, 2017. A total of 7604 individuals aged between 45 and 79 were included in our study. Dietary patterns were established through factor analysis and the dietary pattern factor scores were divided into quartiles (Q1-Q4). The relationship between dietary patterns and diabetes mellitus was analyzed with multivariate logistic regression model. RESULTS: Out of the total of 7604 middle-aged and older rural adults in Xinxiang County, Henan Province, 1604 had diabetes mellitus, suggesting a 21.1% prevalence of diabetes mellitus. Factor analysis was used to establish four dietary patterns, namely animal-based diet, vegetable-egg diet, mixed diet and traditional diet. Subjects of these four dietary patterns displayed different demographic characteristics. There were no statistical difference in anthropometricor clinical indicators between the quartile with the lowest dietary pattern factor score (Q1) and the quartile with the highest dietary pattern factor score (Q4) for subjects with animal-based diet ( P>0.05). Compared with those in the Q1 quartile of vegetable-egg diet, subjects in the Q4 quartile of vegetable-egg diet showed lower levels of high-density lipoprotein cholesterol (HDL-C), along with different distribution of fasting blood glucose (FBG), showing statistically significant difference ( P<0.05). In comparison to subjects in Q1 quartile of mixed diet, those in Q4 quartile showed lower levels of systolic blood pressure (SBP), the difference being statistically significant ( P<0.05). In the traditional diet group, subjects in the Q4 quartile had lower waist circumference (WC), but higher levels of HDL-C than those of subjects in Q1 quartile. In addition, the distribution of glycated-hemoglobin (HbA1c) and FBG were different, the difference being statistically significant ( P<0.05). The results of multivariate logistic regression analysis demonstrated that traditional diet could be a protective factor of diabetes mellitus (odds ratio [ OR]=0.810, 95% CI: 0.690-0.952, P trend<0.05) after adjusting for multiple confounding factors. CONCLUSION: The prevalence of diabetes in middle-aged and older rural residents is relatively high in Xinxiang County, Henan Province, and there may be a protective relationship between traditional diet and diabetes mellitus.
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Diabetes Mellitus , População Rural , Adolescente , Adulto , Idoso , Animais , China/epidemiologia , Estudos Transversais , Diabetes Mellitus/epidemiologia , Dieta , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de RiscoRESUMO
Fritillariae Bulbus are the most commonly used antitussive and edible herbs in China. Based on UPLC-QTOF-MS and UPLC-QQQ-MS, the validated MRM-based non-targeted quantitative method was applied to determinate the contents of 48 Fritillaria alkaloids (FAs) in three Fritillaria species (F. thunbergii Miq., F. unibracteata and F. ussuriensis). The RNA-Seq results showed that gene transcript levels have different expression patterns in three Fritillaria species. Based on transcriptome data, the full-length cDNA sequences of squalene epoxidase gene were cloned and characterized. Natural evolution of squalene epoxidase genes resulted in four mutations (C236R, M489L, G510A and K517R) in three Fritillaria species. Molecular docking analysis showed that the 236 residue is located inside the pocket and the binding center while other three residues are located on the surface of the protein. Functional verification indicated the mutations of SQE (C236R) could effectively increase the activity of SQE and obtain higher yield of 2,3-oxidosqualene in recombinant yeast. And the mutations of SQE (M489L and G510A), which increased the hydrophobicity of the protein surface, could also enhance the activity of SQE. This study provides major insights into the metabolites differentiation of FAs biosynthesis, and a firm foundation for the quality control and metabolic engineering of Fritillariae bulbus.
Assuntos
Fritillaria/enzimologia , Esqualeno Mono-Oxigenase/metabolismo , Alcaloides/metabolismo , Cromatografia Líquida de Alta Pressão , DNA Complementar/genética , Simulação de Acoplamento Molecular , Mutação/genética , Filogenia , Alinhamento de Sequência , Esqualeno Mono-Oxigenase/genéticaRESUMO
Alkaloids are a widespread group of basic compounds in herbal medicines and have attracted great interest due to various pharmaceutical activities and desirable druggability. Their distinctive structures make chromatographic separation fairly difficult. Peak tailing, poor resolution, and inferior column-to-column reproducibility are common obstacles to overcome. In order to provide a valuable reference, the methodologies and/or strategies on liquid chromatographic separation of alkaloids in herbal medicines proposed from 2012 to 2019 are thoroughly summarized.