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Herbal medicines, particularly traditional Chinese medicines (TCMs), are a rich source of natural products with significant therapeutic potential. However, understanding their mechanisms of action is challenging due to the complexity of their multi-ingredient compositions. We introduced Herb-CMap, a multimodal fusion framework leveraging protein-protein interactions and herb-perturbed gene expression signatures. Utilizing a network-based heat diffusion algorithm, Herb-CMap creates a connectivity map linking herb perturbations to their therapeutic targets, thereby facilitating the prioritization of active ingredients. As a case study, we applied Herb-CMap to Suhuang antitussive capsule (Suhuang), a TCM formula used for treating cough variant asthma (CVA). Using in vivo rat models, our analysis established the transcriptomic signatures of Suhuang and identified its key compounds, such as quercetin and luteolin, and their target genes, including IL17A, PIK3CB, PIK3CD, AKT1, and TNF. These drug-target interactions inhibit the IL-17 signaling pathway and deactivate PI3K, AKT, and NF-κB, effectively reducing lung inflammation and alleviating CVA. The study demonstrates the efficacy of Herb-CMap in elucidating the molecular mechanisms of herbal medicines, offering valuable insights for advancing drug discovery in TCM.
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Antitussígenos , Medicamentos de Ervas Chinesas , Medicina Tradicional Chinesa , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Ratos , Antitussígenos/farmacologia , Antitussígenos/uso terapêutico , Mapas de Interação de Proteínas/efeitos dos fármacos , Asma/tratamento farmacológico , Asma/metabolismo , Asma/genética , Transdução de Sinais/efeitos dos fármacos , Tosse/tratamento farmacológico , Transcriptoma , HumanosRESUMO
Elucidating the folding energy landscape of membrane proteins is essential to the understanding of the proteins' stabilizing forces, folding mechanisms, biogenesis, and quality control. This is not a trivial task because the reversible control of folding is inherently difficult in a lipid bilayer environment. Recently, novel methods have been developed, each of which has a unique strength in investigating specific aspects of membrane protein folding. Among such methods, steric trapping is a versatile strategy allowing a reversible control of membrane protein folding with minimal perturbation of native protein-water and protein-lipid interactions. In a nutshell, steric trapping exploits the coupling of spontaneous denaturation of a doubly biotinylated protein to the simultaneous binding of bulky monovalent streptavidin molecules. This strategy has been evolved to investigate key elements of membrane protein folding such as thermodynamic stability, spontaneous denaturation rates, conformational features of the denatured states, and cooperativity of stabilizing interactions. In this review, we describe the critical methodological advancement, limitation, and outlook of the steric trapping strategy.
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Proteínas de Membrana , Dobramento de Proteína , Termodinâmica , Proteínas de Membrana/química , Proteínas de Membrana/metabolismo , Desnaturação Proteica , Bicamadas Lipídicas/química , Bicamadas Lipídicas/metabolismo , Estreptavidina/química , Biotinilação/métodosRESUMO
Background: Tumors' growth processes result in spatial heterogeneity, with the development of tumor subregions (i.e., habitats) having unique biologic characteristics. Objective: To develop and validate a habitat model combining tumor and peritumoral radiomics features on chest CT for predicting invasiveness of lung adenocarcinoma. Methods: This retrospective study included 1156 patients (mean age, 57.5 years; 464 male, 692 female) from three centers and a public dataset, who underwent chest CT before lung adenocarcinoma resection (variable date ranges across datasets). Patients from one center formed training (n=500) and validation (n=215) sets; patients from the other sources formed three external test sets (n=249, 113, 79). For each patient, a single nodule was manually segmented on chest CT. The nodule segmentation was combined with an automatically generated 4-mm peritumoral region into a whole-volume volume-of-interest (VOI). A Gaussian mixture model (GMM) identified voxel clusters with similar first-order energy across patients. GMM results were used to divide each patient's whole-volume VOI into multiple habitats, defined consistently across patients. Radiomic features were extracted from each habitat. After feature selection, a habitat model was developed for predicting invasiveness, using pathologic assessment as a reference. An integrated model was constructed, combining features extracted from habitats and whole-volume VOIs. Model performance was evaluated, including in subgroups based on nodule density (pure ground-glass, part-solid, solid). Results: Invasive cancer was diagnosed in 625/1156 patients. GMM identified four as the optimal number of voxel clusters and thus of per-patient tumor habitats. The habitat model had AUC of 0.932 in the validation set, and 0.881, 0.880, and 0.764 in the three external test sets. The integrated model had AUC of 0.947 in the validation set and 0.936, 0.908, and 0.800 in the three external test sets. In the three external test sets combined, across nodule densities, AUCs for the habitat model were 0.836-0.969 and for the integrated model were 0.846-0.917. Conclusions: Habitat imaging combining tumoral and peritumoral radiomic features could help predict lung adenocarcinoma invasiveness. Prediction is improved when combining information on tumor subregions and the tumor overall. Clinical Impact: The findings may aid personalized preoperative assessments to guide clinical decision-making in lung adenocarcinoma.
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Tuta absoluta is one of the most destructive and invasive insect pests throughout the world. It feeds on numerous solanaceous plant species and has developed resistance to most types of popular insecticides. Tetraniliprole is a novel diamide chemical agent that acts as a modulator of the ryanodine receptor. To establish T. absoluta susceptibility to tetraniliprole and to understand potential mechanisms of resistance, we monitored 18 field populations of T. absoluta collected from northern China. One field-evolved resistant population, Huailai (HL), showed moderate resistance to tetraniliprole (36.2-fold) in comparison with susceptible strain YN-S. Assays of cross-resistance, synergism, metabolic enzyme activity, and inheritance of resistance were performed with YN-S strain and HL population. The latter displayed 12.2- and 6.7-fold cross-resistance to chlorantraniliprole and flubendiamide, respectively, but little cross-resistance to broflanilide (1.6-fold), spinosad (2.1-fold), metaflumizone (1.5-fold), or indoxacarb (2.8-fold). Genetic analyses revealed that tetraniliprole resistance in HL population was autosomal, incompletely dominant, and polygenic. Piperonyl butoxide was found to significantly increase tetraniliprole toxicity, and enzymatic activities of P450 monooxygenase and glutathione S-transferase were significantly higher in HL than YN-S population. These results enhance our knowledge of the inheritance and mechanism of tetraniliprole resistance, enabling future optimization of resistance management strategies.
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Resistência a Inseticidas , Inseticidas , Mariposas , Animais , Resistência a Inseticidas/genética , Inseticidas/farmacologia , China , Mariposas/efeitos dos fármacos , Mariposas/genética , Larva/efeitos dos fármacos , Larva/genéticaRESUMO
A Gram-stain-positive, aerobic actinomycete strain, designated KLBMP 8922T, was isolated from a soil sample collected from weathering dolomite crust in Guizhou Province, PR China. KLBMP 8922T showed the 16S rRNA gene similarities to Yinghuangia seranimata CCTCC AA 206006T (98.7â%), Yinghuangia catbensis VN07A0015T (98.3â%) and Yinghuangia aomiensis M24DS4T (98.2â%). The taxonomic status of this strain was investigated by using a polyphasic approach. The aerial mycelia of KLBMP 8922T formed spore chains, and spores were cylindrical with smooth surfaces. The whole-cell sugars were ribose, mannose and galactose with traces of glucose and xylose. The diagnostic amino acids of the cell wall were ll-diaminopimelic acid, alanine and glutamic acid. The predominant menaquinones were MK-9(H6) and MK-9(H8). The diagnostic phospholipids were diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositolmannoside, phosphatidylethanolamine, an unidentified phospholipid and an unidentified lipid. The major cellular fatty acids (>10â%) were iso-C15â:â0, iso-C16â:â0 and iso-C16â:â1H. The genomic DNA G+C content was 72.0 mol%. The digital DNA-DNA hybridization (dDDH) value between KLBMP 8922T and Y. seranimata CCTCC AA 206006T was 24.1â%, and the average nucleotide identity (ANI) value was 81.0â%. On the basis of a combination of morphological, chemotaxonomic and phylogenetic characteristics, strain KLBMP 8922T represents a novel species of the genus Yinghuangia for which the name Yinghuangia soli sp. nov. is proposed. The type strain was KLBMP 8922T (= CGMCC 1.19360T = NBRC 115572T).
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Ácidos Graxos , Solo , Ácidos Graxos/química , Filogenia , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Fosfolipídeos/químicaRESUMO
Strain KLBMP 9083T, a novel actinobacterium, was isolated from weathered soils collected from a karst area in Anshun, Guizhou Province, PR China. The taxonomic position of strain KLBMP 9083T was studied using the polyphasic approach. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain KLBMP 9083T formed a stabilized monophyletic clade with its closest relative strain Antribacter gilvus CGMCC 1.13856T (98.4â% 16S rRNA gene sequence similarity). The peptidoglycan hydrolysates contained alanine, glutamic acid, threonine and lysine. The polar lipids were composed of diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, an unidentified phosphoglycolipid, an unidentified phospholipid and an unidentified glycolipid. The predominant menaquinones were MK-9(H8) (87.1â%), MK-9(H6) (7.3â%) and MK-9(H4) (5.6â%). The major fatty acids (>10â%) were anteiso-C15â:â0 and iso-C15â:â0. The genomic DNA G+C content was 72.3 mol%. The digital DNA-DNA hybridization and average nucleotide identity values between strain KLBMP 9083T and A. gilvus CGMCC 1.13856T were 23.4 and 79.9â%, respectively. On the basis of morphological, chemotaxonomic and phylogenetic characteristics, strain KLBMP 9083T represents a novel species of the genus Antribacter, for which the name Antribacter soli sp. nov. is proposed. The type strain is KLBMP 9083T (=CGMCC 4.7737T=NBRC 115577T).
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Actinobacteria , Actinomycetales , Ácidos Graxos/química , Solo , Filogenia , RNA Ribossômico 16S/genética , DNA Bacteriano/genética , Composição de Bases , Técnicas de Tipagem Bacteriana , Análise de Sequência de DNA , Fosfolipídeos , Vitamina K 2RESUMO
BACKGROUND AND AIM: Growing studies have demonstrated clinical benefits of fecal microbiota transplantation (FMT) therapy (administered by colonoscopy, enema, or both) for active ulcerative colitis (UC). This study aimed to evaluate the cost-effectiveness of standard treatment with and without FMT therapy for mild-to-moderate active UC from the perspective of US healthcare provider. METHODS: A 10-year Markov model was developed to evaluate the costs and quality-adjusted life-years (QALYs) of standard treatment plus FMT therapy versus standard treatment alone. Model inputs were retrieved from publish data in literature. Base-case and sensitivity analyses were performed. RESULTS: In the base-case analysis, standard treatment plus FMT therapy was more effective than standard treatment alone (by 0.068 QALYs). Comparing to standard treatment alone, standard treatment plus FMT therapy varied from cost-saving to incremental cost, subject to the number of FMT administrations. One-way sensitivity analysis identified the relative risk of achieving remission with FMT therapy to be the most influential factor on the incremental cost-effectiveness ratio of standard treatment plus FMT therapy. Monte-Carlo simulations showed that standard treatment plus FMT therapy with 3 and 6 administrations per FMT course was cost-effective (at willingness-to-pay threshold = 50 000 USD/QALY) in 90.77% and 67.03% of time, respectively. CONCLUSIONS: Standard treatment plus FMT therapy appears to be more effective in gaining higher QALYs than standard therapy alone for patients with mild-to-moderate active UC. Cost-effectiveness of standard treatment plus FMT therapy is highly subject to the relative improvement in achieving remission with standard therapy plus FMT therapy and number of FMT administrations per FMT course.
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Colite Ulcerativa , Transplante de Microbiota Fecal , Humanos , Colite Ulcerativa/terapia , Análise de Custo-Efetividade , Análise Custo-Benefício , Enema , Resultado do TratamentoRESUMO
PM2.5 is one of the most harmful air pollutants affecting sustainable economic and social development in China. The analysis of influencing factors affecting PM2.5 concentration is significant for the improvement of air quality. In this study, three typical urban agglomerations in China (BeijingâTianjinâHebei [BTH], the Yangtze River Delta [YRD], and the Pearl River Delta [PRD]) were studied using innovative trend analysis, a Bayesian statistical model, and partial wavelet and multiwavelet coherence to analyze PM2.5 concentration variations and multi-scale coupled oscillations between PM2.5 concentration and air pollutants/meteorological factors. The results showed that: (1) PM2.5 concentration time-series showed significant downward trends, which decreased as follows: BTH > YRD > PRD. The higher the pollution level, the greater the change trend. In BTH and the PRD, PM2.5 had obvious trends and seasonal change points; whereas, the PM2.5 time-series change point in the YRD was not obvious. (2) PM2.5 had significant intermittent resonance cycles with air pollutants and meteorological factors in different time domains. There were differences in the main controlling factors affecting PM2.5 among the three urban agglomerations. (3) The explanatory ability of air pollutant combinations for variations in PM2.5 was higher than that of meteorological factor combinations. However, the synergistic effect of air pollutants/meteorological factors could better explain the PM2.5 concentration variations on all time-frequency scales. The results of this study provide a reference for ecological improvement as well as collaborative governance of air pollution.
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Endothelial dysfunction (ED) contributes to the pathologic process underlying macrovascular complications, a common complication of type 2 diabetes mellitus (T2DM). Soluble endoglin (sEng) shed from the extracellular domain of the entire endoglin molecule blocks endothelial protection mediated by transforming growth factor-beta 1 (TGF-ß1). The reactive hyperemia index (RHI), which is determined by reactive hyperemia peripheral arterial tonometry (RH-PAT), is a new index with which to evaluate ED. This study determined the changes in serum sEng levels in newly-diagnosed (untreated) T2DM patients and the correlation with the RHI. The T2DM group included 34 newly-diagnosed T2DM patients, while the control group included 53 healthy adults. The clinical data from the two groups were evaluated retrospectively. The intima-media thickness (IMT) of the common carotid artery (CCA) and the ankle-brachial index (ABI) of both legs were used to assess structural vascular changes. The serum sEng level was determined using an ELISA kit. Endothelial function was assessed using RH-PAT and the RHI was computed. The serum sEng level in the T2DM group was significantly greater than the control group, although the RHI was significantly lower in the T2DM group (p < 0.05). The serum sEng level was negatively correlated with the RHI in T2DM patents (r = 0.354, p = 0.041). The serum sEng level, CCA-IMT, and ABI were not significantly correlated with T2DM (p > 0.05). In summary, among newly-diagnosed T2DM patients, the serum sEng levels were inversely correlated with the RHI, and an elevated sEng level may be associated with ED.
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Diabetes Mellitus Tipo 2 , Hiperemia , Adulto , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Endoglina , Estudos Retrospectivos , Espessura Intima-Media Carotídea , Endotélio VascularRESUMO
Packing interaction is a critical driving force in the folding of helical membrane proteins. Despite the importance, packing defects (i.e., cavities including voids, pockets, and pores) are prevalent in membrane-integral enzymes, channels, transporters, and receptors, playing essential roles in function. Then, a question arises regarding how the two competing requirements, packing for stability vs. cavities for function, are reconciled in membrane protein structures. Here, using the intramembrane protease GlpG of Escherichiacoli as a model and cavity-filling mutation as a probe, we tested the impacts of native cavities on the thermodynamic stability and function of a membrane protein. We find several stabilizing mutations which induce substantial activity reduction without distorting the active site. Notably, these mutations are all mapped onto the regions of conformational flexibility and functional importance, indicating that the cavities facilitate functional movement of GlpG while compromising the stability. Experiment and molecular dynamics simulation suggest that the stabilization is induced by the coupling between enhanced protein packing and weakly unfavorable lipid desolvation, or solely by favorable lipid solvation on the cavities. Our result suggests that, stabilized by the relatively weak interactions with lipids, cavities are accommodated in membrane proteins without severe energetic cost, which, in turn, serve as a platform to fine-tune the balance between stability and flexibility for optimal activity.
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Proteínas de Ligação a DNA/química , Endopeptidases/química , Proteínas de Escherichia coli/química , Proteínas de Membrana/química , Domínio Catalítico , Proteínas de Ligação a DNA/metabolismo , Endopeptidases/metabolismo , Proteínas de Escherichia coli/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Modelos Moleculares , Simulação de Dinâmica Molecular , Mutação , Conformação Proteica , Dobramento de Proteína , Estabilidade Proteica , Serina Endopeptidases/químicaRESUMO
OBJECTIVES: To explore the relationship between atherogenic index of plasma (AIP) and childhood asthma. METHODS: This retrospective study included 86 children with asthma admitted to the Changzhou Second People's Hospital Affiliated to Nanjing Medical University from July 2020 to August 2022 as the asthma group and 149 healthy children undergoing physical examination during the same period as the control group. Metabolic parameters including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and blood glucose, as well as general information of the children such as height, weight, body mass index, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, and feeding history, were collected. Multivariable logistic regression analysis was used to study the relationship between AIP, triglycerides, and high-density lipoprotein cholesterol and asthma. The value of AIP, triglycerides, and high-density lipoprotein cholesterol for predicting asthma was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: The AIP and triglyceride levels in the asthma group were significantly higher than those in the control group, while high-density lipoprotein cholesterol was significantly lower (P<0.05). However, there was no significant difference in total cholesterol and low-density lipoprotein cholesterol between the two groups (P>0.05). Before and after adjusting for height, weight, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, feeding method, and blood glucose, multivariable logistic regression analysis showed that AIP, triglycerides, and high-density lipoprotein cholesterol were associated with asthma (P<0.05). ROC curve analysis showed that the optimal cutoff value for predicting asthma with AIP was -0.333, with a sensitivity of 80.2%, specificity of 55.0%, positive predictive value of 50.71%, and negative predictive value of 82.85%. The area under the curve (AUC) for AIP in predicting asthma was significantly higher than that for triglycerides (P=0.009), but there was no significant difference in AUC between AIP and high-density lipoprotein cholesterol (P=0.686). CONCLUSIONS: AIP, triglycerides, and high-density lipoprotein cholesterol are all associated with asthma. AIP has a higher value for predicting asthma than triglycerides and comparable value to high-density lipoprotein cholesterol.
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Asma , Dermatite , Humanos , Criança , Estudos Retrospectivos , Glicemia , Triglicerídeos , HDL-Colesterol , LDL-Colesterol , Asma/etiologia , Fatores de RiscoRESUMO
DNA methyltransferase 1 (DNMT1) shows close link with heart disease. This study aimed to define the role DNMT1 plays in heart failure and determine the underlying mechanism. Expression of microRNA (miR)-152-3p, DNMT1, E26 transformation specific-1 (ETS1) and ras homolog gene family member H (RhoH) was determined by RT-qPCR and/or western blot analysis. The interaction between miR-152-3p and ETS1 was predicted and verified. Methylation of the miR-152-3p promoter region was assessed using methylation-specific PCR. H9c2 cells were chosen for in vitro assays to examine the regulatory role of DNMT1 in autophagy and mitophagy with respect to miR-152-3p/ETS1/RhoH. Doxorubicin (DOX)-induced rat models of heart failure were employed for in vivo validation. DNMT1 expression was upregulated in the heart tissues of DOX-induced rats, where it showed an inverse correlation with miR-152-3p expression. Moreover, DNMT1 was shown to enhance methylation of the miR-152-3p promoter region and suppress its expression, leading to inhibition of mitophagy in H9c2 cells. In addition, DNMT1 enhanced expression of ETS1, which further elevated RhoH expression. Moreover, ETS1-elevated RhoH reduced cell viability and promoted autophagy and mitophagy in H9c2 cells upon treatment with DOX. Next, in vivo results demonstrated that depletion of DNMT1 protected rats from heart failure in a miR-152-3p/ETS1/RhoH-dependent manner. Overall, these findings indicate that DNMT1 may inhibit expression of miR-152-3p by promoting the methylation of miR-152-3p and enhancing the expression of ETS1, thereby inducing RHOH transcriptional activation and inhibiting mitochondrial autophagy, ultimately promoting the development of heart failure.
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DNA (Citosina-5-)-Metiltransferase 1 , Insuficiência Cardíaca , Animais , DNA (Citosina-5-)-Metiltransferase 1/genética , DNA (Citosina-5-)-Metiltransferase 1/metabolismo , Metilação de DNA , Insuficiência Cardíaca/genética , MicroRNAs/genética , Mitofagia/genética , Proteína Proto-Oncogênica c-ets-1/genética , Ratos , Proteínas rho de Ligação ao GTP/genéticaRESUMO
BACKGROUND: The transition from pro-inflammatory M1 phenotype to anti-inflammatory M2 phenotype presents a novel therapeutic strategy for chronic pain. OBJECTIVE: We investigated the role of microglia polarization in cancer-induced bone pain (CIBP), as well as the role of the P2X7 receptor in modulating M1 to M2 polarization. METHODS: Walker-256 breast cancer cells were administered into tibias of female rats to induce bone cancer-associated cancer. RESULTS: During bone cancer development, the P2X7 receptor and M1 microglia markers were upregulated. In contrast, inhibition of the P2X7 receptor by BBG, a blood-brain barrier-permeable P2X7R-specific antagonist, alleviated the pain and promoted microglia polarization toward the M2 phenotype, while suppressing the M1 phenotype in vivo and in vitro. CONCLUSION: P2X7 receptor-mediated spinal microglia polarization is involved in alleviation of CIBP. Therefore, P2X7R is a potential option for CIBP treatment.
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Microglia , Neoplasias , Animais , Feminino , Microglia/fisiologia , Dor , Fenótipo , Ratos , Receptores Purinérgicos P2X7RESUMO
We report a scheme to measure the broadband frequency response of photodetectors (PDs) with the capacity of self-calibration. The optical carrier at f 0 is modulated through one modulator, and this modulator is driven by a microwave signal with a fixed frequency f 1 to produce the carrier-suppressed double sideband optical signals f 0-f 1 and f 0+f 1. The frequency interval of the optical signals is 2f 1. Subsequently, the two optical signals are sent to another modulator driven by a swept microwave signal f m. Two pairs of carrier-suppressed double sideband signals with a high signal-to-noise ratio are generated. The frequencies of these signals are f 0-f 1-f m,f 0-f 1+f m, f 0+f 1-f m, and f 0+f 1+f m. After the PD under test, the frequency response can be extracted from the amplitude of the microwave signals at 2f 1, 2f 1-2f m, and 2f 1+2f m. Two PDs in our laboratory are experimentally characterized from 0.1 to 40 GHz with a resolution of 100 MHz. Compared with the traditional vector network analyzer swept method, the proposed method extends the measurement range from f m(max) to 2f 1+2f m(max) and has the capacity of self-calibration to eliminate the influence caused by the modulator frequency response on the measurement results.
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SIGNIFICANCE: We demonstrate the clinical correlation between the vitamin A level with chalazion in East Chinese children. Vitamin A deficiency is likely to be a potential cause of childhood chalazion. PURPOSE: Chalazion is the most common lid inflammatory lesion of the eyelid, which can be caused by retention of tarsal gland secretions. Studies have revealed that vitamin deficiency is an essential risk factor for children with chalazion. In this study, we measured the serum levels of vitamin A and 25-hydroxyvitamin D (25(OH)D), in patients with chalazion. METHODS: The study included 180 subjects (90 patients with chalazion and 90 control healthy subjects) with an average age of 4.13 ± 2.01 years, and 47.8% of whom were female. Serums came from blood samples collected and used to measure the levels of vitamin A and 25(OH)D. RESULTS: Both groups had statistically similar baseline characteristics, including age and body mass index. The average serum vitamin A levels in patients with chalazion (0.54 ± 0.15 µmol/L) were significantly lower than in their control counterparts (0.60 ± 0.15 µmol/L; P = .01). There was no significant difference in the serum 25(OH)D levels between the patients (70.15 ± 19.73 nmol/L) and control subjects (71.64 ± 24.46 nmol/L). The percentage of vitamin A deficiency in chalazion group (52.2%) was much higher than the control counterparts (28.6%; P = .001). The percentage of 25(OH)D deficiency showed no significant difference between patients with chalazion and control subjects (58.9 vs. 56.7%). CONCLUSIONS: Low serum vitamin A was significantly associated with chalazion in children. The serum 25(OH)D level exhibited no correlation with chalazion.
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Calázio , Deficiência de Vitamina A , Deficiência de Vitamina D , Calázio/complicações , Calázio/diagnóstico , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Vitamina A , Deficiência de Vitamina A/diagnóstico , Deficiência de Vitamina A/epidemiologia , Deficiência de Vitamina D/complicações , VitaminasRESUMO
BACKGROUND AND AIM: Recent clinical findings showed proactive therapeutic drug monitoring (TDM) of adalimumab (ADL) to improve sustained remission rate in pediatric patients with Crohn's disease (CD). The present study aimed to evaluate the potential cost-effectiveness of proactive versus reactive TDM of ADL in pediatric patients with CD from the perspective of the US health-care provider. METHODS: A Markov model was constructed to estimate outcomes of proactive versus reactive TDM of ADL in a hypothetical cohort of pediatric CD patients who were in remission on ADL maintenance treatment. Model inputs were derived from published literature and public data. Model outcomes included CD-related direct medical cost and quality-adjusted life-years (QALYs). Sensitivity analyses were performed to examine the robustness of base-case results. RESULTS: When compared with the reactive TDM group, the proactive TDM group saved 0.1960 QALYs at lower cost by USD2021 over a 3-year time frame in base-case analysis. One-way sensitivity analysis showed the ADL drug cost to be the most influential factor. Probabilistic sensitivity analysis of 10 000 Monte-Carlo simulations found the proactive TDM group to gain 0.1958 QALYs (95% confidence interval [CI] 0.1950-0.1966; P < 0.001) and save USD2037 (95%CI USD1943-2131; P < 0.001). CONCLUSIONS: Proactive TDM for ADL seems to gain higher QALYs at lower cost in pediatric CD patients.
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Adalimumab , Doença de Crohn , Monitoramento de Medicamentos , Adalimumab/uso terapêutico , Criança , Análise Custo-Benefício , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , HumanosRESUMO
BACKGROUND: The COVID-19 pandemic has caused patients to avoid seeking medical care. Provision of telemonitoring programs in addition to usual care has demonstrated improved effectiveness in managing patients with heart failure (HF). OBJECTIVE: We aimed to examine the potential clinical and health economic outcomes of a telemonitoring program for management of patients with HF during the COVID-19 pandemic from the perspective of health care providers in Hong Kong. METHODS: A Markov model was designed to compare the outcomes of a care under COVID-19 (CUC) group and a telemonitoring plus CUC group (telemonitoring group) in a hypothetical cohort of older patients with HF in Hong Kong. The model outcome measures were direct medical cost, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio. Sensitivity analyses were performed to examine the model assumptions and the robustness of the base-case results. RESULTS: In the base-case analysis, the telemonitoring group showed a higher QALY gain (1.9007) at a higher cost (US $15,888) compared to the CUC group (1.8345 QALYs at US $15,603). Adopting US $48,937/QALY (1 × the gross domestic product per capita of Hong Kong) as the willingness-to-pay threshold, telemonitoring was accepted as a highly cost-effective strategy, with an incremental cost-effective ratio of US $4292/QALY. No threshold value was identified in the deterministic sensitivity analysis. In the probabilistic sensitivity analysis, telemonitoring was accepted as cost-effective in 99.22% of 10,000 Monte Carlo simulations. CONCLUSIONS: Compared to the current outpatient care alone under the COVID-19 pandemic, the addition of telemonitoring-mediated management to the current care for patients with HF appears to be a highly cost-effective strategy from the perspective of health care providers in Hong Kong.
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Assistência Ambulatorial , COVID-19/complicações , Análise de Dados , Insuficiência Cardíaca/epidemiologia , Método de Monte Carlo , Telemedicina/economia , Telemedicina/métodos , Assistência Ambulatorial/economia , Assistência Ambulatorial/métodos , COVID-19/epidemiologia , Estudos de Coortes , Análise Custo-Benefício , Hong Kong/epidemiologia , Humanos , Cadeias de Markov , Pandemias , Anos de Vida Ajustados por Qualidade de Vida , SARS-CoV-2RESUMO
BACKGROUND: Circular RNAs (circRNAs) have received considerable attention in human cancer research. However, many circRNAs remain to be detected. In our study, we determined novel circRNAs and investigated their effects on bladder cancer (BCa). METHODS: Microarray dataset GSE92675 was downloaded from Gene Expression Omnibus (GEO). Then, we combined computational biology with quantitative real-time polymerase chain reaction (qRT-PCR) to select related circRNAs in BCa. The selected circRNA-microRNA (miRNA)-messenger RNA (mRNA) regulatory subnetwork was determined by Gene Oncology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. RESULTS: The regulatory network constructed from the microarray dataset (GSE92675) contained 49 differentially expressed circRNAs (DECs). GO and KEGG analyses showed that the MAPK and PI3K-AKT signaling pathways were statistically significant. On the basis of qRT-PCR and the degree value calculated by the cytoHubba plugin of Cytoscape, hsa_circ_0011385 was finally confirmed. The subnetwork around hsa_circ_0011385 was constructed. In addition, we created a protein-protein interaction (PPI) network composed of 67 nodes and 274 edges after removing independent nodes. GO and KEGG analyses showed that hubgenes were involved in cell cycle activities. Moreover, they could be regulated by miRNAs and play an eventful role in BCa pathogenesis. CONCLUSIONS: We proposed a novel circRNA-miRNA-mRNA network related to BCa pathogenesis. This network might be a new molecular biomarker and could be used to develop potential treatment strategies for BCa.
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Satellite laser altimetry can obtain submeter or even centimeter-level surface elevation information over a large range. However, the laser will inevitably be affected by clouds during transmission through the atmosphere, which seriously affects the accuracy of altimetry. In this paper, based on laser altimetry data, cloud optical depth inversion was realized by using the Fernald method. The influence of clouds on the echo waveform data was analyzed with actual data, and a method of cloud scattering error correction was proposed. The existing error correction methods are mostly based on the results of semi-analytical Monte Carlo simulations. In observations, it is difficult to synchronously obtain the parameters required for simulation, which significantly limits the method. Therefore, a method for correcting the cloud scattering error of satellite laser altimetry data based on an exponential model is also proposed. The experimental results show that when the cloud optical depth is 0-2, the root mean square error of the model is 0.05, which can correct the height measurement deviation caused by the cloud to within 5 cm and improve the availability of the laser height measurement data affected by the cloud scattering.
RESUMO
Invasive aspergillosis (IA) is a life-threatening disease impacting immunocompromised individuals. Standard treatments of IA, including polyenes and azoles, suffer from high toxicity and emerging resistance, leading to the need to develop new antifungal agents with novel mechanisms of action. Ergosterol biosynthesis is a classic target for antifungals, and squalene synthase (SQS) catalyzes the first committed step in ergosterol biosynthesis in Aspergillus spp. making SQS of interest in the context of antifungal development. Here, we cloned, expressed, purified and characterized SQS from the pathogen Aspergillus flavus (AfSQS), confirming that it produced squalene. To identify potential leads targeting AfSQS, we tested known squalene synthase inhibitors, zaragozic acid and the phosphonosulfonate BPH-652, finding that they were potent inhibitors. We then screened a library of 744 compounds from the National Cancer Institute (NCI) Diversity Set V for inhibition activity. 20 hits were identified and IC50 values were determined using dose-response curves. 14 compounds that interfered with the assay were excluded and the remaining 6 compounds were analyzed for drug-likeness, resulting in one compound, celastrol, which had an AfSQS IC50 value of 830â¯nM. Enzyme inhibition kinetics revealed that celastrol binds to AfSQS in a noncompetitive manner, but did not bind covalently. Since celastrol is also known to inhibit growth of the highly virulent Aspergillus fumigatus by inhibiting flavin-dependent monooxygenase siderophore A (SidA, under iron starvation conditions), it may be a promising multi-target lead for antifungal development.