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Excessive accumulation of reduced nicotinamide adenine dinucleotide (NADH) within biological organisms is closely associated with many diseases. It remains a challenge to efficiently convert superfluous and detrimental NADH to NAD+. NADH oxidase (NOX) is a crucial oxidoreductase that catalyzes the oxidation of NADH to NAD+. Herein, M1M2 (Mi=V/Mn/Fe/Co/Cu/Mo/Rh/Ru/Pd, i = 1 or 2) mated-atom nanozymes (MANs) are designed by mimicking natural enzymes with polymetallic active centers. Excitingly, RhCo MAN possesses excellent and sustainable NOX-like activity, with Km-NADH (16.11 µM) being lower than that of NOX-mimics reported so far. Thus, RhCo MAN can significantly promote the regeneration of NAD+ and regulate macrophage polarization toward the M2 phenotype through down-regulation of TLR4 expression, which may help to recover skin regeneration. However, RhRu MAN with peroxidase-like activity and RhMn MAN with superoxide dismutase-like activity exhibit little modulating effects on eczema. This work provides a new strategy to inhibit skin inflammation and promote skin regeneration.
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Neurodegeneration disorders, such as Alzheimer's disease (AD), have garnered significant attention due to their impact on individuals and society as a whole. Understanding the mechanisms behind these disorders and developing effective therapy strategies is of utmost importance. One potential therapeutic target that has emerged is Rho-associated coiled-coil containing protein kinase 2 (ROCK2), as its accumulation and activity have been closely linked to memory loss. In this report, we present the findings of a recent discovery involving a new molecule that has the ability to competitively inhibit ROCK2 activity. This molecule was identified through the utilization of a DNA-encoded library (DEL) screening platform. Following selection against ROCK2, an off-DNA compound was synthesized and examined to ascertain its inhibitory properties, selectivity, mechanism of action, and binding mode analysis. From the screening, compound CH-2 has demonstrated an IC50 value of 28 nM against ROCK2, while exhibiting a 5-fold selectivity over ROCK1. Further analysis through molecular docking has provided insights into the specific binding modes of this compound. Our findings suggest that DEL selection offers a rapid method for identifying new inhibitors. Among these, the CH-2 compound shows promise as a potential ROCK2 inhibitor and warrants further investigation.
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Doença de Alzheimer , Quinases Associadas a rho , Humanos , Simulação de Acoplamento Molecular , Quinases Associadas a rho/metabolismo , Doença de Alzheimer/metabolismo , DNA/genética , Trifosfato de AdenosinaRESUMO
For metal-based phosphate adsorbents, the dispersity and utilization of surface metal active sites are crucial factors in their adsorption performance and synthesis cost. In this study, a biochar material modified with amorphous Zr-Ce (carbonate) oxides (BZCCO-13) was synthesized for the phosphate uptake, and the adsorption process was enhanced by magnetic field. The beside-magnetic field was shown to have a better influence than under-magnetic field on adsorption, with maximum adsorption capacities (123.67 mg P/g) 1.14-fold greater than that without magnetic field. The beside-magnetic field could also accelerate the adsorption rate, and the time to reach 90% maximum adsorption capacity decreased by 83%. BZCCO-13 has a wide range of application pHs from 5.0 to 10.0, with great selectivity and reusability. The results of XPS and ELNES showed that the "magnetophoresis" of Ce3+ under the magnetic field was the main reason for the enhanced adsorption performance. In addition, increased surface roughness, pore size and oxygen vacancies, enhanced mass transfer by Lorentz force under a magnetic field, all beneficially influenced the adsorption process. The mechanism of phosphate adsorption by BZCCO-13 could be attributed to electrostatic attraction and CO32-dominated ligand exchange. This study not only provided an effective strategy for designing highly effective phosphate adsorbents, but also provides a new light on the application of rare earth metal-based adsorbent in magnetic field.
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Carvão Vegetal , Fosfatos , Zircônio , Adsorção , Carvão Vegetal/química , Zircônio/química , Fosfatos/química , Campos Magnéticos , Óxidos/química , Carbonatos/químicaRESUMO
Protein glycosylation is a type of protein post-translational modification. One specific example is the modification of proteins with O-linked ß-N-acetylglucosamine (O-GlcNAc) and O-linked α-N-acetylgalactosamine (O-GalNAc). Enhanced levels of both O-GalNAc and O-GlcNAc in bladder cancer (BlCa) have been reported previously. However, the interplay between O-GalNAc and O-GlcNAc has yet to be explored. Herein, we find that the expression level of core1 ß-1,3-galactosyltransferase (C1GalT1), which is responsible for extending and maturing mucin-type O-glycans, is increased in BlCa. This increase is accompanied by O-GlcNAc modification of C1GalT1. This modification stabilizes C1GalT1 expression and strengthens its interaction with its chaperone Cosmc. Mutation at Thr229 or Thr233 attenuates C1GalT1 stability and facilitates its degradation via the proteasome pathway. Furthermore, a decrease in C1GalT1 inhibits the pro-tumorigenic effect on bladder cancer cells by suppressing glycolysis.
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There is an unmet need for easy-to-visualize drug carriers that can deliver therapeutic cargoes deep into solid tumors. Herein, we report the preparation of ultrasmall luminescent imine-based lanthanide nanocages, Eu60 and Tb60 (collectively Ln60 ), designed to encapsulate anticancer chemotherapeutics for tumor therapy. The as-prepared nanocages possess large cavities suitable for the encapsulation of doxorubicin (DOX), yielding DOX@Ln60 nanocages with diameters around 5â nm. DOX@Ln60 are efficiently internalized by breast cancer cells, allowing the cells to be visualized via the intrinsic luminescent property of Ln(III). Once internalized, the acidic intracellular microenvironment promotes imine bond cleavage and the release of the loaded DOX. DOX@Ln60 inhibits DNA replication and triggers tumor cell apoptosis. In a murine triple negative breast cancer (TNBC) model, DOX@Ln60 was found to inhibit tumor growth with negligible side effects on normal tissues. It proved more effective than various controls, including DOX and Ln60 . The present nanocages thus point the way to the development of precise nanomedicines for tumor imaging and therapy.
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Elementos da Série dos Lantanídeos , Nanopartículas , Animais , Camundongos , Linhagem Celular Tumoral , Sistemas de Liberação de Medicamentos/métodos , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Portadores de Fármacos/química , Iminas , Nanopartículas/químicaRESUMO
Trap-assisted non-radiative recombination losses and moisture-induced degradation significantly impede the development of highly efficient and stable inverted (p-i-n) perovskite solar cells (PSCs), which require high-quality perovskite bulk. In this research, we mitigate these challenges by integrating thermally stable perovskite layers with Lewis base covalent organic frameworks (COFs). The ordered pore structure and surface binding groups of COFs facilitate cyclic, multi-site chelation with undercoordinated lead ions, enhancing the perovskite quality across both its bulk and grain boundaries. This process not only reduces defects but also promotes improved energy alignment through n-type doping at the surface. The inclusion of COF dopants in p-i-n devices achieves power conversion efficiencies (PCEs) of 25.64% (certified 24.94%) for a 0.0748-cm2 device and 23.49% for a 1-cm2 device. Remarkably, these devices retain 81% of their initial PCE after 978 hours of accelerated aging at 85ËC, demonstrating remarkable durability. Additionally, COF-doped devices demonstrate excellent stability under illumination and in moist conditions, even without encapsulation.
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Cervical cancer (CC) is a highly fatal gynecological malignancy due to its high metastasis and recurrence rate. Circular RNA (circRNA) has been regarded as a regulator of CC. However, the underlying molecular mechanism of circ_0005615 in CC remains unclear. The levels of circ_0005615, miR-138-5p, and lysine demethylase 2A (KDM2A) were measured using qRT-PCR or western blot. Cell proliferation was assessed by Cell Counting Kit-8, 5-ethynyl-2'-deoxyuridine, and colony formation experiments. Cell invasion and migration were tested by transwell assay and wound healing assay. Flow cytometry and Caspase-Glo 3/7 Assay kit were used to analyze cell apoptosis. The expression of proliferation-related and apoptosis-related markers was detected by western blot. The binding relationships among circ_0005615, miR-138-5p, and KDM2A were verified by dual-luciferase reporter assay or RNA immunoprecipitation assay. Xenograft assay was applied to detect the effect of circ_0005615 in vivo. Circ_0005615 and KDM2A were upregulated, while miR-138-5p was downregulated in CC tissues and cells. Circ_0005615 knockdown retarded cell proliferation, migration, and invasion, while promoting apoptosis. Besides, circ_0005615 sponged miR-138-5p, and miR-138-5p could target KDM2A. miR-138-5p inhibitor reversed the regulation of circ_0005615 knockdown on CC cell growth and metastasis, and KDM2A overexpression also abolished the inhibitory effect of miR-138-5p on CC cell growth and metastasis. In addition, we also discovered that circ_0005615 silencing inhibited CC tumor growth in vivo. Circ_0005615 acted as a tumor promoter in CC by regulating the miR-138-5p/KDM2A pathway.
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Proteínas F-Box , MicroRNAs , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Transformação Celular Neoplásica , Apoptose , Western Blotting , Proliferação de Células , MicroRNAs/genética , Linhagem Celular Tumoral , Histona Desmetilases com o Domínio Jumonji/genéticaRESUMO
Phosphorus (P) removal from wastewater is critical for ecosystem operation and resource recovery. To facilitate the recycling of the used absorbents through balancing their adsorption and desorption performance on P, in this work, a novel porous magnetic La(OH)3-loaded MAPTAC/chitosan (CTS)/polyethyleneimine (PEI) ternary composite hydrogel (p-MTCH-La(OH)3) with enhanced bifunctional adsorption sites was synthesized by simultaneous dissolution of pre-embedded CaCO3 and CTS powder, followed by grafting PEI and loading La. Hierarchical porous channels promoted good dispersion of La(OH)3, bringing an excellent P adsorption capacity of 107.23 ± 4.96 mg P/g at neutral condition. PEI grafted with CTS increased the surface charge and enhanced the electrostatic attraction, which facilitated the desorption of P. The porous structure and abundant active sites also facilitated rapid adsorption with an adsorption rate constant of 0.1 g mg-1 h-1. p-MTCH-La(OH)3 maintained effective P adsorption despite co-existence with competing substances and after 5 cycles. Further mechanistic analysis indicated that La-P inner sphere complexation and LaPO4 crystalline transformation were the main pathways for P removal. However, electrostatic interactions contributed 17.5%-46.7% of the adsorption amount during the first 30 min of rapid adsorption, enabling 92.8% of the adsorbed P at this stage to be desorbed by alkaline solution. Based on the variations of adsorption and desorption capacity with adsorption time, a rapid unsaturated adsorption of 1-2 h was proposed to facilitate the recycling of the adsorbent. This study proposed a method to promote P adsorption and desorption by enhancing bifunctional adsorption sites, and proved that p-MTCH-La(OH)3 is a promising phosphate adsorbent.
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Fósforo , Poluentes Químicos da Água , Hidrogéis , Lantânio/química , Porosidade , Ecossistema , Fosfatos/química , Adsorção , Cátions , Cinética , Poluentes Químicos da Água/químicaRESUMO
Referred somatic pain triggered by hyperalgesia is common in patients with inflammatory bowel disease (IBD). It was reported that sprouting of sympathetic nerve fibers into the dorsal root ganglion (DGR) and neurogenic inflammation were related to neuropathic pain, the excitability of neurons, and afferents. The purpose of the study was to explore the potential and mechanism of electroacupuncture (EA) at Zusanli (ST36) for the intervention of colon inflammation and hyperalgesia. Sprague-Dawley (SD) was randomly divided into four groups, including control, model, EA, and sham-EA. Our results showed EA treatment significantly attenuated dextran sulfate sodium- (DSS-) induced colorectal lesions and inflammatory cytokine secretion, such as TNF-α, IL-1ß, PGE2, and IL-6. EA also inhibited mechanical and thermal pain hypersensitivities of colitis rats. Importantly, EA effectively abrogated the promotion effect of DSS on ipsilateral lumbar 6 (L6) DRG sympathetic-sensory coupling, manifested as the sprouting of tyrosine hydroxylase- (TH-) positive sympathetic fibers into sensory neurons and colocalization of and calcitonin gene-related peptide (CGRP). Furthermore, EA at Zusanli (ST36) activated neurogenic inflammation, characterized by decreased expression of substance P (SP), hyaluronic acid (HA), bradykinin (BK), and prostacyclin (PGI2) in colitis rat skin tissues corresponding to the L6 DRG. Mechanically, EA treatment reduced the activation of the TRPV1/CGRP, ERK, and TLR4 signaling pathways in L6 DRG of colitis rats. Taken together, we presumed that EA treatment improved colon inflammation and hyperalgesia, potentially by suppressing the sprouting of sympathetic nerve fibers into the L6 DGR and neurogenic inflammation via deactivating the TRPV1/CGRP, ERK, and TLR4 signaling pathways.
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Colite , Eletroacupuntura , Neuralgia , Dor Nociceptiva , Ratos , Animais , Ratos Sprague-Dawley , Hiperalgesia/metabolismo , Eletroacupuntura/métodos , Gânglios Espinais/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Inflamação Neurogênica/metabolismo , Receptor 4 Toll-Like/metabolismo , Neuralgia/metabolismo , Dor Nociceptiva/metabolismoRESUMO
OBJECTIVE: There is a paucity of research on the association between bile acids (BAs) levels and all-cause death in patients with diabetes mellitus (DM) on maintenance hemodialysis (MHD). This study aimed to investigate the clinical characteristics of patients with DM on MHD according to different BAs levels and their impact on prognosis. METHODS: A retrospective cohort of 1,081 patients on hemodialysis at Xindu People's Hospital and the First Affiliated Hospital of Chengdu Medical College were enrolled. Demographic and clinical characteristics were collected. The relationship between BAs and all-cause death risk was fitted using restricted cubic splines (RCS), and the BAs cutoff value was calculated. Patients were divided into low and high BAs groups based on the cutoff value. The primary endpoint was all-cause death and the secondary outcomes were deaths from cardiovascular events. RESULTS: Finally, 387 patients with DM on MHD were included. The median BAs level of all patients was 4.0 µmol/L. The RCS-based BAs cutoff value was 3.5 µmol/L. The BAs levels correlated negatively with total cholesterol, low-density lipoprotein, and blood calcium levels. During the follow-up, 21.7% of the patients died. The multivariate Cox regression analysis demonstrated that patients with DM on MHD with higher BAs were associated independently with a decreased risk of all-cause death (HR =0.55; 95% CI, 0.35-0.81, p = 0.01) compared to those with lower BAs levels. CONCLUSIONS: Higher BAs levels were associated with lower lipid levels in patients with DM on MHD. BAs is an independent risk factor for all-cause death in patients with DM on MHD.
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Diabetes Mellitus , Diálise Renal , Humanos , Estudos Retrospectivos , Diálise Renal/efeitos adversos , Diabetes Mellitus/epidemiologia , Fatores de Risco , PrognósticoRESUMO
The Zn-ion micro-supercapacitor (ZMSC) is a promising candidate for developing miniaturized and integrated energy storage devices. To achieve high-performance functional groups with simple processing to composite with rod-like active PANI fibers, we prepared exfoliated graphene (EG) with an appropriate amount of O-containing functional groups. The appropriate O content simultaneously facilitated self-assembly of the EG and PANI fibers and maintained the electric conductivity of the composite, producing a free-standing EG/PANI film without additional conductive additives or current collectors. As an interdigital electrode for the ZMSC, the EG/PANI film showed ultrahigh capacitance of 1.8 F cm-2 at 2.6 mA cm-2 (361.3 F g-1 at 0.5 A g-1) and landmark energy density of 755.8 µWh cm-2 at 2.3 mW cm-2 (148.2 Wh kg-1 at 451.7 W kg-1). The facile preparation of the high-performance EG/PANI electrode provides a potential path for practical applications with ZMSCs.
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Grafite , Capacitância Elétrica , Condutividade Elétrica , Eletrodos , ZincoRESUMO
BACKGROUND: RNA secondary structure is very important for deciphering cell's activity and disease occurrence. The first method which was used by the academics to predict this structure is biological experiment, But this method is too expensive, causing the promotion to be affected. Then, computing methods emerged, which has good efficiency and low cost. However, the accuracy of computing methods are not satisfactory. Many machine learning methods have also been applied to this area, but the accuracy has not improved significantly. Deep learning has matured and achieves great success in many areas such as computer vision and natural language processing. It uses neural network which is a kind of structure that has good functionality and versatility, but its effect is highly correlated with the quantity and quality of the data. At present, there is no model with high accuracy, low data dependence and high convenience in predicting RNA secondary structure. RESULTS: This paper designs a neural network called LTPConstraint to predict RNA secondary structure. The network is based on many network structure such as Bidirectional LSTM, Transformer and generator. It also uses transfer learning to train modelso that the data dependence can be reduced. CONCLUSIONS: LTPConstraint has achieved high accuracy in RNA secondary structure prediction. Compared with the previous methods, the accuracy improves obviously both in predicting the structure with pseudoknot and the structure without pseudoknot. At the same time, LTPConstraint is easy to operate and can achieve result very quickly.
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Redes Neurais de Computação , RNA , Aprendizado de Máquina , Estrutura Secundária de Proteína , RNA/químicaRESUMO
BACKGROUND: The comorbidity of tuberculosis (TB) and diabetes mellitus (DM) is a global health concern. Metformin is commonly used in DM but the potential effectiveness in comorbid patients is uncertain. This retrospective study aims to investigate the effect of metformin on TB-DM comorbidity and construct prediction models. METHODS: Patients diagnosed with TB-DM in West China Hospital were retrospectively enrolled from Nov 2013 to Sep 2019. Electronic health records of patients were extracted. Two-month smear conversion (2SC) was considered an outcome indicator of TB. Univariate and multivariate logistic regression (LR) were used to assess the role of metformin and other independent predictors. Meanwhile, prediction models were built by LR, elastic net regression, support vector machine, k-nearest neighbors, and random forest. RESULTS: A total of 927 individuals were recruited, among which 408 (44.01%) were metformin-exposed patients. A higher 2SC rate was observed in the metformin users. Other impact factors such as smoking, glucose, and creatinine levels were also identified. Multivariable models were then constructed using filtered variables. The support vector machine model yields the highest AUC (0.808, 95% CI: 0.767-0.849) and specificity (83.24%). LR model outperformed others in terms of sensitivity (69.71%). CONCLUSION: This retrospective study of a large population from southwestern China provides strong clinical evidence for the positive effects of metformin in TB-DM. Metformin is associated with a better therapeutic outcome and promising for the adjuvant therapy of TB-DM. Furthermore, a combination of support vector machine and LR models is recommended to discriminate the patients with poor treatment outcomes.
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Diabetes Mellitus , Metformina , Tuberculose , Humanos , Metformina/uso terapêutico , Estudos Retrospectivos , Hipoglicemiantes/uso terapêutico , Tuberculose/complicações , Tuberculose/tratamento farmacológico , Tuberculose/epidemiologia , Diabetes Mellitus/tratamento farmacológico , Diabetes Mellitus/epidemiologia , ComorbidadeRESUMO
Cationic hydrogels have received great attention to control eutrophication and recycle phosphate. In this study, a type of La(OH)3 loaded magnetic MAPTAC-based cationic hydrogel (La(OH)3@MMCH) was developed as a potential adsorbent for enhanced phosphate removal from aqueous environment. La(OH)3@MMCH exhibited high adsorption capacity of 105.72±5.99 mg P/g, and reached equilibrium within 2 hr. La(OH)3@MMCH could perform effectively in a wide pH range from 3.0 to 9.0 and in the presence of coexisting ions (including SO42-, Cl-, NO3-, HCO3-, SiO44- and HA). The adsorption-desorption experiment indicated that La(OH)3@MMCH could be easily regenerated by using NaOH-NaCl as the desorption agent, and 73.3% adsorption capacity remained after five cycles. Moreover, La(OH)3@MMCH was employed to treat surface water with phosphate concentration of 1.90 mg/L and showed great removal efficiency of 95.21%. Actually, MMCH showed high surface charge density of 34.38-59.38 meq/kg in the pH range from 3.0 to 11.0 and great swelling ratio of 3014.57% within 24 h, indicating that MMCH could produce the enhanced Donnan membrane effect to pre-permeate phosphate. Furthermore, the bifunctional structure of La(OH)3@MMCH enabled it to capture phosphate through electrostatic attraction and ligand exchange. All the results prove that La(OH)3@MMCH is a promising adsorbent for eutrophication control and phosphate recovery.
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Fosfatos , Poluentes Químicos da Água , Adsorção , Cloreto de Amônio , Hidrogéis , Cinética , Lantânio , Fenômenos Magnéticos , MetacrilatosRESUMO
Bimetallic oxides composites have received an increasing attention as promising adsorbents for aqueous phosphate (P) removal in recent years. In this study, a novel magnetic composite MZLCO was prepared by hybridizing amorphous Zr-La (carbonate) oxides (ZLCO) with nano-Fe3O4 through a one-pot solvothermal method for efficient phosphate adsorption. Our optimum sample of MZLCO-45 exhibited a high Langmuir maximum adsorption capacity of 96.16 mg P/g and performed well even at low phosphate concentration. The phosphate adsorption kinetics by MZLCO-45 fitted well with the pseudo-second-order model, and the adsorption capacity could reach 79% of the ultimate value within the first 60 min. The phosphate adsorption process was highly pH-dependent, and MZLCO-45 performed well over a wide pH range of 2.0-8.0. Moreover, MZLCO-45 showed a strong selectivity to phosphate in the presence of competing ions (Cl-, NO3-, SO42-, HCO3-, Ca2+, and Mg2+) and a good reusability using the eluent of NaOH/NaCl mixture, then 64% adsorption capacity remained after ten recycles. The initial 2.0 mg P/L in municipal wastewater and surface water could be efficiently reduced to below 0.1mg P/L by 0.07 g/L MZLCO-45, and the phosphate removal efficiencies were 95.7% and 96.21%, respectively. Phosphate adsorption mechanisms by MZLCO-45 could be attributed to electrostatic attraction and the inner-sphere complexation via ligand exchange forming Zr/La-O-P, -OH and CO32- groups on MZLCO-45 surface played important roles in the ligand exchange process. The existence of oxygen vacancies could accelerate the phosphate absorption rate of the MZLCO-45 composites.
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Lantânio , Óxidos , Aceleração , Carbonatos , Ligantes , Oxigênio , Fosfatos , Eletricidade Estática , ÁguaRESUMO
We systematically summarized tuberculosis (TB)-related non-coding RNA (ncRNA) diagnostic panels, validated and compared panel performance. We searched TB-related ncRNA panels in PubMed, OVID and Web of Science up to 28 February 2020, and available datasets in GEO, SRA and EBI ArrayExpress up to 1 March 2020. We rebuilt models and synthesized the results of each model in validation sets by bivariate mixed models. Specificity at 90% sensitivity, area under curve (AUC) and inconsistence index (I2 ) were calculated. NcRNA biofunctions were analysed. Nineteen models based on 18 ncRNA panels (miRNA, lncRNA, circRNA and snoRNA panels) and 18 datasets were included. Limited available datasets only allowed to evaluate miRNA panels further. Cui 2017 and Latorre 2015 exhibited specificity >70% at 90% sensitivity and AUC >80% in all validation sets. Cui 2017 showed higher specificity at 90% sensitivity (92%) and AUC (95%) and lower heterogeneity (I2 = 0%) in ethological-confirmation validation sets. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis indicated that most ncRNAs in panels involved in immune cell activation, oxidative stress, and Wnt and MAPK signalling pathway. Cui 2017 outperformed other models in both all available and aetiological-confirmed validation sets, meeting the criteria of target product profile of WHO. This work provided a basis for clinical choice of TB-related ncRNA diagnostic panels to a certain extent.
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RNA não Traduzido/genética , Tuberculose/diagnóstico , Tuberculose/genética , Adolescente , Adulto , Bases de Dados Genéticas , Etnicidade , Regulação da Expressão Gênica , Ontologia Genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , RNA não Traduzido/metabolismo , Análise de Regressão , Reprodutibilidade dos TestesRESUMO
Inflammation has an important role in ischemia-reperfusion (I/R) injury. Artesunate (ART) has anti-microbial and anti-inflammatory pharmacological activities, and it is used for various types of serious malaria, including cerebral malaria. ART maintains a high concentration in the brain but little is known about the neuroprotective effect of ART against brain I/R injury. We studied the neuroprotection of ART against brain I/R injury and its underlying mechanism. In this study, rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h. After 24 h of reperfusion, neurological deficits, cerebrum water content, infarct volume, hematoxylin-eosin (H&E)-staining, myeloperoxidase (MPO) activity, and proinflammatory cytokine levels were measured. Administration of 20, 40, 80, and 160 mg/kg ART intraperitoneally (i.p.) 10 min after MCAO significantly decreased brain water content and improved neurological deficits in a dose-dependent manner. An 80 mg/kg dosage was optimal. ART significantly reduced infarct volume, suppressed MPO activity and diminished the expressions of toll-like receptor (TLR)-4, MyD88, nuclear factor-κB (NF-κB), tumor necrosis factor (TNF)-α, and interleukin (IL)-6 in the area of the ischemic cortex. The neuroprotective action of ART against focal cerebral I/R injury might be due to the attenuation of inflammation through the TLR-4/NF-κB pathway.
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Artesunato/uso terapêutico , Infarto da Artéria Cerebral Média/tratamento farmacológico , Fármacos Neuroprotetores/uso terapêutico , Traumatismo por Reperfusão/tratamento farmacológico , Animais , Artesunato/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/imunologia , Encéfalo/patologia , Infarto da Artéria Cerebral Média/imunologia , Infarto da Artéria Cerebral Média/patologia , Interleucina-6/imunologia , Masculino , Fármacos Neuroprotetores/farmacologia , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Ratos Sprague-Dawley , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/patologia , Receptor 4 Toll-Like/imunologia , Fator de Transcrição RelA/imunologia , Fator de Necrose Tumoral alfa/imunologiaRESUMO
Vital signs monitoring in physical activity (PA) is of great significance in daily healthcare. Impulse Radio Ultra-WideBand (IR-UWB) radar provides a contactless vital signs detection approach with advantages in range resolution and penetration. Several researches have verified the feasibility of IR-UWB radar monitoring when the target keeps still. However, various body movements are induced by PA, which lead to severe signal distortion and interfere vital signs extraction. To address this challenge, a novel joint chest-abdomen cardiopulmonary signal estimation approach is proposed to detect breath and heartbeat simultaneously using IR-UWB radars. The movements of target chest and abdomen are detected by two IR-UWB radars, respectively. Considering the signal overlapping of vital signs and body motion artifacts, Empirical Wavelet Transform (EWT) is applied on received radar signals to remove clutter and mitigate movement interference. Moreover, improved EWT with frequency segmentation refinement is applied on each radar to decompose vital signals of target chest and abdomen to vital sign-related sub-signals, respectively. After that, based on the thoracoabdominal movement correlation, cross-correlation functions are calculated among chest and abdomen sub-signals to estimate breath and heartbeat. The experiments are conducted under three kinds of PA situations and two general body movements, the results of which indicate the effectiveness and superiority of the proposed approach.
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Radar , Processamento de Sinais Assistido por Computador , Algoritmos , Exercício Físico , Frequência Cardíaca , Sinais VitaisRESUMO
We conducted a prospective, multicenter, randomized, controlled clinical trial to compare the efficacy and safety of high-dose dexamethasone (HD-DXM) plus recombinant human thrombopoietin (rhTPO), vs HD-DXM alone in newly diagnosed adult immune thrombocytopenia (ITP) patients. Enrolled patients were randomly assigned to receive DXM plus rhTPO or DXM monotherapy. Another 4-day course of DXM was repeated if response was not achieved by day 10 in both arms. One hundred patients in the HD-DXM plus rhTPO arm and 96 patients in the HD-DXM monotherapy arm were included in the full analysis set. So, HD-DXM plus rhTPO resulted in a higher incidence of initial response (89.0% vs 66.7%, P < .001) and complete response (CR, 75.0% vs 42.7%, P < .001) compared with HD-DXM monotherapy. Response rate at 6 months was also higher in the HD-DXM plus rhTPO arm than that in the HD-DXM monotherapy arm (51.0% vs 36.5%, P = .02; sustained CR: 46.0% vs 32.3%, P = .043). Throughout the follow-up period, the overall duration of response was greater in the HD-DXM plus rhTPO arm compared to the HD-DXM monotherapy arm (P = .04), as estimated by the Kaplan-Meier analysis. The study drugs were generally well tolerated. In conclusion, the combination of HD-DXM with rhTPO significantly improved the initial response and yielded favorable SR in newly diagnosed ITP patients, thus could be further validated as a frontline treatment for ITP. This study is registered as clinicaltrials.gov identifier: NCT01734044.
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Dexametasona/administração & dosagem , Púrpura Trombocitopênica Idiopática , Trombopoetina/administração & dosagem , Adulto , Idoso , Dexametasona/efeitos adversos , Intervalo Livre de Doença , Quimioterapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/mortalidade , Taxa de Sobrevida , Trombopoetina/efeitos adversosRESUMO
Excessive nitrate (NO3-) is among the most problematic surface water and groundwater pollutants. In this study, a type of magnetic cationic hydrogel (MCH) is employed for NO3- adsorption and well characterized herein. Its adsorption capacity is considerably pH-dependent and achieves the optimal adsorption (maximum NO3--adsorption capacity is 95.88 ± 1.24 mg/g) when the pH level is 5.2-8.8. The fitting result using the homogeneous surface diffusion model indicates that the surface/film diffusion controls the adsorption rate, and NO3- approaches the center of MCH particles within 30 min. The diffusion coefficient (Ds) and external mass transfer coefficient (kF) in the liquid phase are 1.15 × 10-6 cm2/min and 4.5 × 10-6 cm/min, respectively. The MCH is employed to treat surface water that contains 10 mg/L of NO3-, and it is found that the optimal magnetic separation time is 1.6 min. The high-efficiency mass transfer and magnetic separation of MCH during the adsorption-regeneration process favors its application in surface water treatment. Furthermore, the study of the mechanism involved reveals that both -N+(CH3)3 groups and NO3- are convoluted in adsorption via electrostatic interactions. It is further found that ion exchange between NO3- and chlorine occurs.