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BACKGROUND: Health literacy measurement lays a solid foundation to identify associations with health outcomes and monitor population health literacy levels over time. In mainland China, most existing health literacy instruments are either knowledge-based or practice-based, making health literacy results incomparable between China and other countries. This study aimed to examine the reliability and validity of the 12-item Health Literacy Population Survey (HLS19-Q12) in a general population of Chinese adults. METHODS: A cross-sectional study was conducted to recruit primary carers of students from 11 schools in Zhengzhou, Henan Province, using convenience cluster sampling. Participants completed an online self-administered survey that collected information on key sociodemographics, health literacy (HLS19-Q12 and a comparison tool: Health Literacy Questionnaire (HLQ)), and health-related outcomes. Using the COnsensus-based Standards for the selection of health status Measurement Instruments (COSMIN) checklist as a guideline, we tested internal consistency, test-retest reliability, content validity, structural validity, concurrent predictive validity, and convergent validity of the HLS19-Q12. RESULTS: Overall, 14,184 participants completed the full survey. The HLS19-Q12 showed excellent internal consistency (Cronbach's α = 0.93), moderate test-retest reliability (intra-class correlation coefficient = 0.54), satisfactory content validity (based on the 12-matrix health literacy model), and strong structural validity (comparative fit index = 0.94, Tucker and Lewis's index of fit = 0.93, root mean square error of approximation = 0.095). Concurrent predictive validity results showed health literacy was associated with both health determinants and health-related outcomes. The HLS19-Q12 had weak to strong correlations (coefficients = 0.24 to 0.42) with the nine scales of the HLQ. Respondents had an average score of 81.6 (± 23.0) when using the HLS19-Q12, with 35.0% and 7.5% having problematic and inadequate levels of health literacy, respectively. CONCLUSIONS: The HLS19-Q12 is a reliable and valid instrument to measure health literacy in our sample. Further validation is needed with a more nationally representative sample of Chinese adults. The HLS19-Q12 could be used as a comprehensive, skills-based, and easy-to-administer health literacy assessment tool integrated into population surveys and intervention evaluations.
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Letramento em Saúde , Adulto , Humanos , China , Estudos Transversais , Reprodutibilidade dos Testes , Inquéritos e QuestionáriosRESUMO
Moonlighting enzymes are multifunctional proteins that perform multiple functions beyond their primary role as catalytic enzymes. Extensive research and clinical practice have demonstrated their pivotal roles in the development and progression of cancer, making them promising targets for drug development. This article delves into multiple notable moonlighting enzymes, including GSK-3, GAPDH, and ENO1, and with a particular emphasis on an enigmatic phosphatase, PTP4A3. We scrutinize their distinct roles in cancer and the mechanisms that dictate their ability to switch roles. Lastly, we discuss the potential of an innovative approach to develop drugs targeting these moonlighting enzymes: target protein degradation. This strategy holds promise for effectively tackling moonlighting enzymes in the context of cancer therapy.
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Quinase 3 da Glicogênio Sintase , Neoplasias , Humanos , Monoéster Fosfórico Hidrolases , Neoplasias/tratamento farmacológico , Catálise , Desenvolvimento de Medicamentos , Proteínas de Neoplasias , Proteínas Tirosina FosfatasesRESUMO
Due to sensitive scaling of the wavelength and the visible-light absorption properties with the device dimension, traditional passive silicon photonic devices with asymmetric waveguide structures cannot achieve polarization control at the visible wavelengths. In this work, a simple and small polarization beam splitter (PBS) for a broad visible-light band, using a tailored silicon nitride (Si3N4) ridge waveguide, is presented, which is based on the distinct optical distribution of two fundamental orthogonal polarized modes in the ridge waveguide. The bending loss for different bending radii and the optical coupling properties of the fundamental modes for different Si3N4 ridge waveguide configurations are analyzed. A PBS composed of a bending ridge waveguide structure and a triple-waveguide directional coupler was fabricated on the Si3N4 thin film. The TM excitation of the device based on a bending ridge waveguide structure shows a polarization extinction ratio (PER) of ≥ 20â dB with 33â nm bandwidth (624-657â nm) and insertion loss (IL) ≤ 1â dB at the through port. The TE excitation of the device, based on a triple-waveguide directional coupler with coupling efficiency distinction between the TE0 and TM0 modes, shows a PER of ≥ 18â dB with 50â nm bandwidth (580-630â nm) and insertion loss (IL) ≤ 1â dB at the cross port. The on-chip Si3N4 PBS device is found to possess the highest known PER at a visible broadband range and small (43â µm) footprint. It should be useful for novel photonic circuit designs and further exploration of Si3N4 PBSs.
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PbS films grown on quartz substrates by the chemical bath deposition method were annealed in an O2 atmosphere to investigate the role of oxygen in the sensitization process at different annealing temperatures. The average grain size of the PbS films gradually increased as the annealing temperature increased from 400 °C to 700 °C. At an annealing temperature of 650 °C, the photoresponsivity and detectivity reached 1.67 A W-1 and 1.22 × 1010 cm Hz1/2 W-1, respectively. The role of oxides in the sensitization process was analyzed in combination with X-ray diffraction and scanning electron microscopy results, and a three-dimensional network model of the sensitization mechanism of PbS films was proposed. During the annealing process, O functioned as a p-type impurity, forming p+-type PbS layers with high hole concentrations on the surface and between the PbS grains. As annealing proceeds, the p+-type PbS layers at the grain boundaries interconnect to form a three-dimensional network structure of hole transport channels, while the unoxidized p-type PbS layers act as electron transport channels. Under bias, photogenerated electron-hole pairs were efficiently separated by the formed p+-p charge separation junction, thereby reducing electron-hole recombination and facilitating a higher infrared response.
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Building contour extraction from high-resolution remote sensing images is a basic task for the reasonable planning of regional construction. Recently, building segmentation methods based on the U-Net network have become popular as they largely improve the segmentation accuracy by applying 'skip connection' to combine high-level and low-level feature information more effectively. Meanwhile, researchers have demonstrated that introducing an attention mechanism into U-Net can enhance local feature expression and improve the performance of building extraction in remote sensing images. In this paper, we intend to explore the effectiveness of the primeval attention gate module and propose the novel Attention Gate Module (AG) based on adjusting the position of 'Resampler' in an attention gate to Sigmoid function for a building extraction task, and a novel Attention Gates U network (AGs-Unet) is further proposed based on AG, which can automatically learn different forms of building structures in high-resolution remote sensing images and realize efficient extraction of building contour. AGs-Unet integrates attention gates with a single U-Net network, in which a series of attention gate modules are added into the 'skip connection' for suppressing the irrelevant and noisy feature responses in the input image to highlight the dominant features of the buildings in the image. AGs-Unet improves the feature selection of the attention map to enhance the ability of feature learning, as well as paying attention to the feature information of small-scale buildings. We conducted the experiments on the WHU building dataset and the INRIA Aerial Image Labeling dataset, in which the proposed AGs-Unet model is compared with several classic models (such as FCN8s, SegNet, U-Net, and DANet) and two state-of-the-art models (such as PISANet, and ARC-Net). The extraction accuracy of each model is evaluated by using three evaluation indexes, namely, overall accuracy, precision, and intersection over union. Experimental results show that the proposed AGs-Unet model can improve the quality of building extraction from high-resolution remote sensing images effectively in terms of prediction performance and result accuracy.
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Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Tecnologia de Sensoriamento RemotoRESUMO
BACKGROUND: The irregular anatomical shape and complex structures of irregular bones make it more difficult to repair and reconstruct bone defects in irregular bones than in the long bones of the extremities. Three-dimensional (3D) printing technology can help to overcome the technical limitations of irregular bone repair by generating simulations that enable structural integration of the lesion area and bone structure of the donor site in all directions and at multiple angles. Thus, personalized and accurate treatment plans for restoring anatomical structure, muscle attachment points, and maximal function can be made. The present study aimed to investigate the ability of 3D printing technology to assist in the repair and reconstruction of scapular aneurysmal ABC defects. METHODS: The study included seven patients with ABCs of the scapula. Based on computed tomography (CT) data for the patient, the scapula (including the defect) and pelvis were reconstructed using Mimics Medical software. The reconstructed scapula model was printed using a 3D printer. Before the operation, the model was used to design the surgical approach and simulate the operation process, to determine the length and radius of the plate and the number and direction of screws, and to determine the bone mass of the ilium and develop reasonable strategies for segmentation and distribution. The operation time, amount of bleeding, length and radius of the plate, and direction and number of screws were recorded. RESULTS: The average duration of follow-up was 25.6 months, and none of the seven patients experienced recurrence during the follow-up period. The surgical approach, the length and radius of internal fixation, and the number and direction of screws were consistent with the designed operation plan. Patients gradually recovered the anatomical structure of the scapula and function of the shoulder joint. CONCLUSIONS: In the treatment of bone defects caused by irregular bone tumors, 3D printing technology combined with surgery has the advantages of less trauma, short operation time, less bleeding and reducing the difficulty of operation, which can reduce the waste of bone graft, and more complete reconstruction of the anatomical structure of the defective bone.
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Cistos Ósseos Aneurismáticos , Cistos Ósseos Aneurismáticos/diagnóstico por imagem , Cistos Ósseos Aneurismáticos/cirurgia , Placas Ósseas , Fixação Interna de Fraturas , Humanos , Impressão Tridimensional , Escápula/diagnóstico por imagem , Escápula/cirurgiaRESUMO
BACKGROUND: Helicobacter pylori (H pylori) infection may be a risk factor for cardiovascular disease (CVD), but the reported researches have given conflicting results. AIMS: To investigate the association between H pylori infection and risk of atherosclerotic CVD. MATERIALS AND METHODS: The studies were retrieved in Embase, PubMed, Web of Science (published from Jan 1, 1990, to Jan 31, 2020, language restrictions: English). All studies included used data from case-control studies and cohort studies of cardiovascular adverse events. Random effect models were used to measure pooled estimates. All data were analyzed with Stata 11.2 SE (StataCorp, College Station, TX). RESULTS: Helicobacter pylori infection increased the risk of adverse cardiovascular events by 51% (40 studies, n = 19 691, odd ratio [OR] = 1.51, 95% confidence interval [CI]: 1.34-1.70). The effect was greater for studies that the type of CVDs was myocardial infarction (MI) and cerebrovascular disease (MI OR = 1.80, 95% CI: 1.42-2.26, cerebrovascular disease OR = 1.54, 95% CI: 1.27-1.89). Meanwhile, CagA seropositive H pylori strains were associated with a significantly increased risk of cardiovascular adverse events based on published research data (OR = 1.73, 95% CI: 1.40-2.14). CONCLUSION: In conclusion, H pylori infection enhanced the risk of atherosclerotic cardiovascular adverse events, especially in some patients with MI and cerebrovascular disease. This study will provide guidance for the targeted prevention and treatment of CVDs. But this association need to be confirmed by more prospective studies.
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Aterosclerose/epidemiologia , Doenças Cardiovasculares , Infecções por Helicobacter , Doenças Cardiovasculares/epidemiologia , Infecções por Helicobacter/epidemiologia , Helicobacter pylori , Humanos , Estudos Prospectivos , Fatores de RiscoRESUMO
Background and objectives: The prognostic role of a disintegrin and metalloproteinase (ADAM) 17 has been widely assessed in gastric cancer. However, the results are inconsistent. We performed a meta-analysis to evaluate the prognostic significance of ADAM17 and its association with clinicopathological parameters. Methods: The databases of PubMed, Web of Science, and Embase were searched for relevant articles published up to April 2020. The reported hazard ratios (HRs) and odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were pooled to evaluate the strength of the association. Stata 12.1 was used to perform statistical analyses. Results: Seven studies, including 1757 patients, were screened for the meta-analysis. Compared with the high ADAM17 expression group, the pooled HR was higher in the low ADAM17 expression group (HR = 2.04, 95% CI 1.66-2.50; I2 = 18.1%; p = 0.299). High ADAM17 expression was also related to the tumor node metastasis (TNM) stages (OR = 4.09, 95% CI 1.85-9.04; I2 = 84.1%; p = 0.000), lymph node metastasis (OR = 3.08, 95% CI 1.13-8.36; I2 = 79.7%; p = 0.007), and ages (OR = 1.65, 95% CI 1.24-2.21; I2 = 0%; p = 0.692) of the gastric patients. Conclusions: This meta-analysis revealed that ADAM17 is a significant biomarker for poor prognosis in gastric cancer.
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Proteína ADAM17/análise , Neoplasias Gástricas/genética , Biomarcadores Tumorais/análise , Humanos , Prognóstico , Neoplasias Gástricas/mortalidade , Análise de SobrevidaRESUMO
Background and Objectives: To perform a systematic review and meta-analysis with the aim of determining the relationship between H. pylori infection and psoriasis. Methods: Pubmed, Embase, China National Knowledge Infrastructure (CNKI), and Web of Science were searched for articles published up to July, 2019. Review Manager 5.3 and Stata 12.0 were used for statistical analyses. Results: The initial database search resulted in 204 articles. Through exclusion and screening, 11 studies involving a total of 1741 participants were finally included in this meta-analysis. The odds ratio (OR) of H. pylori infection rate in the psoriasis group was significantly higher than that in the control group (OR = 1.19, 95% CI 1.15-2.52, P = 0.008). Subgroup analysis showed that no significant difference was detected between the Asia group and the Europe group. As for the methods of H. pylori detection, a statistically significant increase of H. pylori infection in the IgG ELISA test group was detected, compared with the urea breath test group. In addition, analysis based on the severity of psoriasis showed a statistically significant increase of H. pylori infection in moderate and severe psoriasis patients (OR = 2.27; 95% CI: 1.42-3.63, I2 = 27%), but not in the mild psoriasis patients (OR = 1.10; 95% CI: 0.79-1.54, I2 = 0%). Conclusion: H. pylori infection is associated with psoriasis, and psoriasis patients with H. pylori infection have higher Psoriasis Area and Severity Index (PASI) scores. The findings are of considerable significance for the clinical practices.
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Infecções por Helicobacter/complicações , Helicobacter pylori/patogenicidade , Psoríase/etiologia , Ensaio de Imunoadsorção Enzimática , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Humanos , Razão de Chances , Psoríase/imunologia , Psoríase/microbiologia , Índice de Gravidade de DoençaAssuntos
Neoplasias da Mama , Neoplasias da Mama/terapia , China , Feminino , Humanos , Pulmão , Atenção Primária à Saúde , República da CoreiaRESUMO
It is uncommon for tire explosion related injuries on the lower extremity. The bilateral lower extremities were injured by tire explosion when the patient was seated in a bus. She sustained an open fracture with partial bone loss in the right calcaneus (a comminuted fracture in the right ankle joint) and a closed comminuted fracture in the left tibia and fibula. This damage was caused by uncontacted tire explosion, thanks to a thick floor between the exploded tire and the patient's feet. This type of injury on lower extremity caused by uncontacted tire explosion was uncommon.
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Fraturas do Tornozelo/etiologia , Explosões , Fíbula/lesões , Fraturas da Tíbia/etiologia , Automóveis , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
Dogs play an important role in rabies transmission throughout the world. In addition to the severe human rabies situation in China, spillover of rabies virus from dogs in recent years has caused rabies outbreaks in sheep, cattle and pigs, showing that there is an increasing threat to other domestic animals. Two livestock rabies outbreaks were caused by dogs in Shanxi province, China from April to October in 2015, resulting in the deaths of 60 sheep, 10 cattle and one donkey. Brain samples from one infected bovine and the donkey were determined to be rabies virus (RABV) positive by fluorescent antibody test (FAT) and reverse transcription polymerase chain reaction (RT-PCR). The complete RABV N genes of the two field strains, together with those of two previously confirmed Shanxi dog strains, were amplified, sequenced and compared phylogenetically with published sequences of the N gene of RABV strains from Shanxi and surrounding provinces. All of the strains from Shanxi province grouped closely, sharing 99.6 %-100 % sequence identity, indicating the wide distribution and transmission of dog-mediated rabies in these areas. This is the first description of donkey rabies symptoms with phylogenetic analysis of RABVs in Shanxi province and surrounding regions. The result emphasizes the need for mandatory dog rabies vaccination and improved public education to eradicate dog rabies transmission.
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Surtos de Doenças , Gado , Vírus da Raiva/isolamento & purificação , Raiva/veterinária , Animais , Encéfalo/virologia , Bovinos , China/epidemiologia , Equidae , Imunofluorescência , Epidemiologia Molecular , Proteínas do Nucleocapsídeo/genética , Filogenia , Raiva/epidemiologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Análise de Sequência de DNA , Homologia de Sequência , OvinosRESUMO
BACKGROUND: Subtrochanteric oblique osteotomy (SOO) has been widely used to reconstruct highly dislocated hips in uncemented total hip arthroplasty. The occurrence of complications can be attributed to the instability of the osteotomy region. The aim of this study was to evaluate the initial stability of SOO in uncemented total hip arthroplasty. MATERIAL AND METHODS: A 3-dimensional finite element femur-stem model was created, and a virtual SOO was performed at 4 oblique angles: 30°, 45°, 60°, and 90°. The von Mises stress distribution in the femur-stem complex and the displacement under different oblique angles were evaluated in the SOO models, in comparison with that of the intact model. RESULTS: The study demonstrated that the distal fragment of the femur bore more stresses than the proximal fragment, and the maximum stress was concentrated in the femoral neck and the cortical bone, which contacted with the distal end of the stem. SOO increased the stress of both the femur and the stem, and fractures may occur in the stress concentration sites. Additionally, comparing the displacement at different oblique angles, the lateral region was larger than that of the medial region on the subtrochanteric osteotomy plane. The minimum micromotion on the osteotomy plane was obtained when the oblique angle was 45°. CONCLUSIONS: The fit and fill of the distal fragment of the femur and the stem is essential for the stability of the subtrochanteric osteotomy region. The optimal oblique angle for SOO appears to be 45°.
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Artroplastia de Quadril/métodos , Fêmur , Osteotomia/métodos , Análise de Elementos Finitos , HumanosRESUMO
Excessive immune activation contributes to the onset of early dysfunction of the maternal-fetal interface, and it is closely linked to the development of pre-eclampsia. However, the effect of specific immune cells on the risk of pre-eclampsia and eclampsia remains controversial. We investigated the causal relationship between immune cells and pre-eclampsia and eclampsia. For exposure, we extracted genetic variants associated with immune cell-related traits, and for outcomes, we used summary genetic data of pre-eclampsia/eclampsia. A two-sample Mendelian randomization (MR) analysis was then performed to assess the causal relationship. Robustness of the MR results was then evaluated through colocalization analysis. We found that genetically proxied circulating lymphocyte absolute count was causally associated with total eclampsia (odds ratio (OR) = 1.53, 95% confidence interval (CI) (1.31-1.79), p = 1.15E - 07) and pre-eclampsia (OR = 1.50, 95% CI (1.28-1.77), p = 9.18E - 07); T cell absolute count was causally associated with total eclampsia (OR = 1.49, 95% CI (1.28-1.73), p = 2.73E - 07) and pre-eclampsia (OR = 1.47, 95% CI (1.25-1.72), p = 1.76E - 06). And CD28- CD25+ CD8+ T cell absolute count was causally associated with total eclampsia (OR = 1.83, 95% CI (1.44-2.32), p = 7.11E - 07) and pre-eclampsia (OR = 1.77, 95% CI (1.38-2.26), p = 6.55E - 06). Colocalization analysis revealed that immune cell-related traits shared the same variant with pre-eclampsia/eclampsia. Our study suggested causal effects of genetic predisposition to high lymphocyte absolute count levels, T cell absolute count, and CD28- CD25+ CD8+ T cell absolute count on eclampsia, particularly pre-eclampsia risk, providing crucial new insights into the potential prevention target for eclampsia and pre-eclampsia.
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Eclampsia , Pré-Eclâmpsia , Gravidez , Feminino , Humanos , Antígenos CD28 , Incidência , LinfócitosRESUMO
The fatty acid-binding protein 1 (FABP1) is a fatty acid transporter protein that is considered as an emerging target for metabolic diseases. Despite forceful evidence that the inhibition of FABP1 is essential for ameliorating NASH, pharmacological control and validation of FABP1 are hindered by a lack of relevant inhibitors as pharmacological tool. Therefore, the development of effective FABP1 inhibitors is a current focus of research. Herein, we firstly reported the comprehensive structure-activity relationship (SAR) study of novel FABP1 inhibitors derived from high throughput screening of our in-house library, which resulting in the identification of the optimal compound 44 (IC50 = 4.46 ± 0.54 µM). Molecular docking studies revealed that 44 forms stable hydrogen bonds with amino acids around the active pocket of FABP1. Moreover, 44 alleviated the typical histological features of fatty liver in NASH mice, including steatosis, lobular inflammation, ballooning and fibrosis. Additionally, 44 has been demonstrated to have lipid metabolism regulating, anti-oxidative stress and hepatoprotective properties. This study might be provided a promising insight into the field of NASH and inspiration for the development of FABP1 inhibitors.
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Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Simulação de Acoplamento Molecular , Metabolismo dos Lipídeos , Fibrose , Proteínas de Ligação a Ácido Graxo/metabolismo , Fígado/metabolismoRESUMO
Gout flare-up, commonly resulting from monosodium urate monohydrate (MSUM) crystallization, has led to painful inflammatory arthritis among hundreds of millions of people. Herein, a kind of hydrogel nanoparticles (HNPs) with specific properties was developed, aimed at providing a promising pathway for MSUM crystallization control. The experimental and molecular dynamics simulation results synchronously indicate that the fabricated HNPs achieve efficient inhibition of MSUM crystallization governed by the mechanism of "host-guest interaction" even under very low-dose administration. HNPs as the host dispersed in the hyperuricemic model effectively lift the relative heterogeneous nucleation barrier of the MSUM crystal and hinder solute aggregation with strong electronegativity and hydrophobicity. The initial appearance of MSUM crystals was then delayed from 94 to 334 h. HNPs as the guest on the surface of the formed crystal can decelerate the growth rate by anchoring ions and occupying the active sites on the surface, and the terminal yield of the MSUM crystal declined to less than 1% of the control group. The good biocompatibility of HNPs (cell viability > 94%) renders it possible for future clinical applications. This study can guide the rational design of inhibitory nanomaterials and the development of their application in the control of relevant pathological crystallization.
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Cristalização , Hidrogéis , Simulação de Dinâmica Molecular , Nanopartículas , Ácido Úrico , Ácido Úrico/química , Hidrogéis/química , Nanopartículas/química , Animais , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Tamanho da Partícula , Íons/química , Propriedades de SuperfícieRESUMO
Histologic spectrum studies in patients revealed fatty acid binding proteins 1 (FABP1) as a potential new target for the treatment of metabolic associated fatty liver disease. However, there is no FABP1 inhibitor has been reported except the first-in-class FABP1 inhibitor bearing acid moiety reported by our laboratory. Herein, we firstly report the structure-activity relationship of novel non-carboxylic acid FABP1 inhibitors, which resulted in the identification of the potent and selective FABP1 inhibitor 30. The IC50 value of compound 30 for subtype FABP4 in the same family was greater than 80 µM. Moreover, compound 30 significantly alleviated the hepatic steatosis in DIO mice, which is equivalent to that of clinical drug obeticholic acid. This study might be provided a promising probe for the development of FABP1 inhibitors and thus can help to further elucidate the pharmacology of FABP1.
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Desenho de Fármacos , Proteínas de Ligação a Ácido Graxo , Proteínas de Ligação a Ácido Graxo/antagonistas & inibidores , Proteínas de Ligação a Ácido Graxo/metabolismo , Animais , Relação Estrutura-Atividade , Camundongos , Humanos , Estrutura Molecular , Relação Dose-Resposta a Droga , Masculino , Camundongos Endogâmicos C57BLRESUMO
Background: Accumulating evidence has highlighted the effects of natural killer (NK) cells on shaping anti-tumor immunity. This study aimed to construct an NK cell marker gene signature (NKMS) to predict prognosis and therapeutic response of clear cell renal cell carcinoma (ccRCC) patients. Methods: Publicly available single-cell and bulk RNA profiles with matched clinical information of ccRCC patients were collected from Gene Expression Omnibus (GEO), The Cancer Genome Atlas (TCGA), ArrayExpress, and International Cancer Genome Consortium (ICGC) databases. A novel NKMS was constructed, and its prognostic value, associated immunogenomic features and predictive capability to immune checkpoint inhibitors (ICIs) and anti-angiogenic therapies were evaluated in ccRCC patients. Results: We identified 52 NK cell marker genes by single-cell RNA-sequencing (scRNA-seq) analysis in GSE152938 and GSE159115. After least absolute shrinkage and selection operator (LASSO) and Cox regression, the most prognostic 7 genes (CLEC2B, PLAC8, CD7, SH3BGRL3, CALM1, KLRF1, and JAK1) composed NKMS using bulk transcriptome from TCGA. Survival and time-dependent receiver operating characteristic (ROC) analysis exhibited exceptional predictive capability of the signature in the training set and two independent validation cohorts (E-MTAB-1980 and RECA-EU cohorts). The seven-gene signature was able to identify patients within high Fuhrman grade (G3-G4) and American Joint Committee on Cancer (AJCC) stage (III-IV). Multivariate analysis confirmed the independent prognostic value of the signature, and a nomogram was built for clinical utility. The high-risk group was characterized by a higher tumor mutation burden (TMB) and greater infiltration of immunocytes, particularly CD8+ T cells, regulatory T (Treg) cells and follicular helper T (Tfh) cells, in parallel with higher expression of genes negatively regulating anti-tumor immunity. Moreover, high-risk tumors exhibited higher richness and diversity of T-cell receptor (TCR) repertoire. In two therapy cohorts of ccRCC patients (PMID32472114 and E-MTAB-3267), we demonstrated that high-risk group showed greater sensitivity to ICIs, whereas the low-risk group was more likely to benefit from anti-angiogenic therapy. Conclusions: We identified a novel signature that can be utilized as an independent predictive biomarker and a tool for selecting the individualized treatment for ccRCC patients.
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On-chip polarization control is in high demand for novel integrated photonic applications such as polarization division multiplexing and quantum communications. However, due to the sensitive scaling of the device dimension with wavelength and the visible-light absorption properties, traditional passive silicon photonic devices with asymmetric waveguide structures cannot achieve polarization control at visible wavelengths. In this paper, a new polarization-splitting mechanism based on energy distributions of the fundamental polarized modes in the r-TiO2 ridge waveguide is investigated. The bending loss for different bending radii and the optical coupling properties of the fundamental modes in different r-TiO2 ridge waveguide configurations are analyzed. In particular, a polarization splitter with a high extinction ratio operating at visible wavelengths based on directional couplers (DCs) in the r-TiO2 ridge waveguide is proposed. Polarization-selective filters based on micro-ring resonators (MRRs) with resonances of only TE or TM polarizations are designed and operated. Our results show that polarization-splitters for visible wavelengths with a high extinction ratio in DC or MRR configurations can be achieved with a simple r-TiO2 ridge waveguide structure.