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BACKGROUND: Several previous studies investigated the associations between temperature and influenza in a single city or region without a national picture. The attributable risk of influenza due to temperature and the corresponding driving factors were unclear. This study aimed to evaluate the spatial distribution characteristics of attributable risk of Influenza-like illness (ILI) caused by adverse temperatures and explore the related driving factors in the United States. METHODS: ILI, meteorological factors, and PM2.5 of 48 states in the United States were collected during 2011-2019. The time-stratified case-crossover design with a distributed lag non-linear model was carried out to evaluate the association between temperature and ILI at the state level. The multivariate meta-analysis was performed to obtain the combined effects at the national level. The attributable fraction (AF) was calculated to assess the ILI burden ascribed to adverse temperatures. The ordinary least square model (OLS), spatial lag model (SLM), and spatial error model (SEM) were utilized to identify driving factors. RESULTS: A total of 7,716,115 ILI cases were included in this study. Overall, the temperature was negatively associated with ILI risk, and lower temperature gave rise to a higher risk of ILI. AF ascribed to adverse temperatures differed across states, from 49.44% (95% eCI: 36.47% ~ 58.68%) in Montana to 6.51% (95% eCI: -6.49% ~ 16.46%) in Wisconsin. At the national level, 29.08% (95% eCI: 27.60% ~ 30.24%) of ILI was attributable to cold. Per 10,000 dollars increase in per-capita income was associated with the increment in AF (OLS: ß = -6.110, P = 0.021; SLM: ß = -5.496, P = 0.022; SEM: ß = -6.150, P = 0.022). CONCLUSION: The cold could enhance the risk of ILI and result in a considerable proportion of ILI disease burden. The ILI burden attributed to cold varied across states and was higher in those states with lower economic status. Targeted prevention programs should be considered to lower the burden of influenza.
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Gripe Humana , Humanos , Estados Unidos/epidemiología , Temperatura , Estudios Cruzados , Gripe Humana/epidemiología , Frío , MontanaRESUMEN
Nanomaterials for biological applications would inevitably encounter and interact with biomolecules, which have a profound impact on the properties, functions, and even fates of both nanomaterials and biomolecules. Among the biomolecules, lysozyme (Lys) is of great importance in defending the bacterial intruder and maintaining health. Here, the interactions between fluorescent gold nanoclusters (AuNCs) (â¼2 nm) capped with different surface ligands and Lys were thoroughly investigated. Fluorescence spectroscopic studies showed that dihydrolipoic acid (DHLA)-capped and glutathione (GSH)-capped AuNCs both quenched the intrinsic fluorescence of Lys by different quenching mechanisms. Agarose gel electrophoresis and zeta-potential assays showed that statistically one DHLA-AuNC could bind one Lys, while one GSH-AuNC could bind 3-4 Lys, providing new examples for the concept of a "protein complex". Activity assays indicated that DHLA-AuNCs heavily inhibited the enzymatic activity of Lys, while GSH-AuNCs had little effect. By synchronous fluorescence and circular dichroism spectroscopic studies, it was deduced that both AuNCs would interact with Lys by electrostatic attractions due to the distinct surface charges, and then DHLA-AuNCs would further interact with Lys by hydrophobic interactions, probably due to the hydrophobic carbon chain of DHLA and the hydrophobic side chains of amino acid residues in Lys, which was proved by the significant secondary structure changes caused by DHLA-AuNCs. Meanwhile, conformational changes induced by GSH-AuNCs with zwitterionic ligands were neglectable. Therefore, this work provided a comprehensive study of the consequences and mechanisms of the interactions between Lys and AuNCs, which was essential for the design and better use of nanomaterials as biological agents.
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Oro , Nanopartículas del Metal , Interacciones Hidrofóbicas e Hidrofílicas , Ligandos , MuramidasaRESUMEN
BACKGROUND: Elevated blood pressure (BP) was associated with higher risk of heart failure, but the relationship between BP-lowering via antihypertensive drugs and diminution of heart failure was inconclusive. This study aimed to estimate the causal association of BP with heart failure, and explore the effects of BP-lowering through different antihypertensive drug classes on heart failure risk using Mendelian randomization analysis with genetic variants as instrument variables. METHODS: Genetic variants associated with BP were derived from UK Biobank ( n â=â317â754) and the genome-wide association study (GWAS) meta-analysis of UK Biobank and International Consortium of Blood Pressure ( n â=â757â601). Heart failure summary association data were contributed by HERMES Consortium (47â309 heart failure cases and 930â014 controls). Inverse variance weighted (IVW) was performed to estimate causality between exposure and outcome, and weighted median was utilized as sensitivity analysis, and Mendelian randomization-Egger regression was used to identify pleiotropy of instrument variables. Multivariable Mendelian randomization (MVMR) was applied to control for the confounders. RESULTS: Genetically predicted SBP and DBP were associated with heart failure [SBP: odds ratio (OR)â=â1.355, 95% confidence interval (CI) 1.201-1.529; DBP: ORâ=â1.348, 95% CI 1.213-1.498] in UK Biobank. Likewise, in the GWAS meta-analysis of UK Biobank and International Consortium of Blood Pressure, the causal associations were observed between SBP, DBP and heart failure (SBP: ORâ=â1.237, 95% CI 1.188-1.289; DBP: ORâ=â1.337, 95% CI 1.245-1.437). Genetically determined ß-blockers and calcium channel blockers (CCBs) were associated with lower risk of heart failure (ß-blockers: ORâ=â0.617, 95% CI 0.453-0.839; CCBs: ORâ=â0.730, 95% CI 0.625-0.851). No association was found between angiotensin receptor blockers (ARBs) and heart failure (ORâ=â1.593, 95% CI 0.647-3.924). When adjusted for smoking, alcohol, physical activity, fruit and vegetable intake, the results were stable. CONCLUSION: Our study indicates causal associations between SBP, DBP, and heart failure, and suggests the preventive effects of heart failure by BP-lowering using ß-blockers and CCBs.
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Antihipertensivos , Insuficiencia Cardíaca , Humanos , Antihipertensivos/uso terapéutico , Antihipertensivos/farmacología , Presión Sanguínea/genética , Análisis de la Aleatorización Mendeliana , Antagonistas de Receptores de Angiotensina/farmacología , Estudio de Asociación del Genoma Completo , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Bloqueadores de los Canales de Calcio/uso terapéutico , Insuficiencia Cardíaca/epidemiología , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/tratamiento farmacológico , Antagonistas Adrenérgicos beta/farmacología , Polimorfismo de Nucleótido SimpleRESUMEN
The quality control of plastic products is an essential aspect of the plastic injection molding (PIM) process. However, the warpage and shrinkage deformations continue to exist because the PIM process is easily interfered with by several related or independent process parameters. Thus, great efforts have been devoted to optimizing process parameters to minimize the warpage and shrinkage deformations of products during the last decades. In this review, we begin by introducing the manufacturing process in PIM and the cause of warpage and shrinkage deformations, followed by the mechanism about how process parameters, like mold temperature, melt temperature, injection rate, injection pressure, holding pressure, holding and cooling duration, affect those defects. Then, we summarize the recent progress of the design of experiments and four advanced methods (artificial neural networks, genetic algorithm, response surface methodology, and Kriging model) on optimizing process parameters to minimize the warpage and shrinkage deformations. In the end, future perspectives of quality control in injection molding machines are discussed.
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AIMS: Previous studies investigated the associations between sleep traits and cardiac diseases, but the evidence for the causal inferences was unclear. This study aimed to explore the causal relationship between sleep and cardiac diseases by virtue of Mendelian randomization (MR). METHODS AND RESULTS: Summary-level data for exposure variables (sleep duration, chronotype, and insomnia) and outcome variables (ischaemic heart disease, atrial fibrillation, myocardial infarction, and heart failure) were derived from UK Biobank. Data from the FinnGen consortium was used as a robustness check. In MR analysis, the inverse variance weighted (IVW) method was applied to infer causality between exposure and outcome. MR-Egger regression was used to identify pleiotropy, and MR-PRESSO outlier test was used to remove the pleiotropy of the genetic instruments. Based on UK Biobank, MR analysis suggested that sleep duration was weakly associated with atrial fibrillation (OR = 0.9999, 95% CI: 0.9998-0.9999) and ischaemic heart disease (OR = 0.9997, 95% CI: 0.9995-0.9998). Insomnia was associated with ischaemic heart disease (OR = 1.0117, 95% CI: 1.0051-1.0183) and myocardial infarction (OR = 1.0049, 95% CI: 1.0019-1.0079). No associations were found between chronotype and cardiac diseases (P > 0.05). We did not find pleiotropy except for insomnia with ischaemic heart disease and myocardial infarction using MR-Egger regression, and MR-PRESSO analysis consistent with IVW. Finally, we obtained the same direction as with UK Biobank using the FinnGen data. CONCLUSIONS: Sleep duration and insomnia might be the potential causal risk factors of cardiac diseases. As the OR was small, these associations are probably not clinically relevant. Further validation studies are needed.
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Fibrilación Atrial , Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Sueño/genética , Infarto del Miocardio/epidemiología , Infarto del Miocardio/genéticaRESUMEN
BACKGROUND: Genome wide association studies (GWAS) have discovered a few of single nucleotide polymorphisms (SNPs) related to major psychiatric disorders. However, it is not completely clear which genes play a pleiotropic role in multiple disorders. The study aimed to identify the pleiotropic genes across five psychiatric disorders using multivariate adaptive association tests. METHODS: Summary statistics of five psychiatric disorders were downloaded from Psychiatric Genomics Consortium. We applied linkage disequilibrium score regression (LDSC) to estimate genetic correlation and conducted tissue and cell type specificity analyses based on Multi-marker Analysis of GenoMic Annotation (MAGMA). Then, we identified the pleiotropic genes using MTaSPUsSet and aSPUs tests. We ultimately performed the functional analysis for pleiotropic genes. RESULTS: We confirmed the significant genetic correlation and brain tissue and neuron specificity among five disorders. 100 pleiotropic genes were detected to be significantly associated with five psychiatric disorders, of which 55 were novel genes. These genes were functionally enriched in neuron differentiation and synaptic transmission. LIMITATIONS: The effect direction of pleiotropic genes couldn't be distinguished due to without individual-level data. CONCLUSION: We identified pleiotropic genes using multivariate adaptive association tests and explored their biological function. The findings may provide novel insight into the development and implementation of prevention and treatment as well as targeted drug discovery in practice.
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Estudio de Asociación del Genoma Completo , Trastornos Mentales , Pleiotropía Genética , Predisposición Genética a la Enfermedad/genética , Humanos , Desequilibrio de Ligamiento , Trastornos Mentales/genética , Polimorfismo de Nucleótido Simple/genéticaRESUMEN
Cu-modified nanoparticles have been designed to mimic peroxidase, and their potent antibacterial and anti-biofilm abilities have been widely investigated. In this study, novel core-shell polydopamine (PDA)/Cu4(OH)6SO4 crystal (PDA/Cu) nanometer rods were prepared. The PDA/Cu nanometer rods show similar kinetic behaviors to chloride-activated peroxidases, exhibit excellent photothermal properties, and are sensitive to the concentrations of pH values and the substrate (i.e., H2O2). PDA/Cu nanometer rods could adhere to the bacteria and catalyze hydrogen peroxide (H2O2) to generate more reactive hydroxy radicals (â¢OH) against Staphylococcus aureus and Escherichia coli, Furthermore, PDA/Cu nanometer rods show enhanced catalytic and photothermal synergistic antibacterial activity. This work provides a simple, inexpensive, and effective strategy for antibacterial applications.
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Long non-coding RNA (lncRNA) FEZF1 antisense RNA 1 (FEZF1-AS1) has been shown to be up-regulated in tumor tissues and cells, and exerts oncogenic effects on various types of malignancies. However, the expression and function of FEZF1-AS1 was still fully unclear in retinoblastoma. The purpose of our study was to investigate the expression and clinical value of FEZF1-AS1 in retinoblastoma patients, and explore the effect of FEZF1-AS1 on retinoblastoma cell proliferation, migration and invasion. In our results, levels of FEZF1-AS1 expression were elevated in retinoblastoma tissue specimens and cell lines compared with adjacent normal retina tissue specimens and human retinal pigment epithelial cell line, respectively. The correlation analysis indicated that high FEZF1-AS1 expression was significantly correlated with present choroidal invasion and optic nerve invasion. Survival analysis suggested that retinoblastoma patients in high FEZF1-AS1 expression group had obviously short disease-free survival (DFS) compared with retinoblastoma patients in low FEZF1-AS1 expression group, and high FEZF1-AS1 expression was an independent unfavorable prognostic factor for DFS in retinoblastoma patients. Loss-of-function study indicated silencing FEZF1-AS1 expression inhibited retinoblastoma cell proliferation, invasion and migration. In conclusion, FEZF1-AS1 functions as an oncogenic lncRNA in retinoblastoma.
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Movimiento Celular , Proliferación Celular , Regulación Neoplásica de la Expresión Génica , Oncogenes , ARN Largo no Codificante/biosíntesis , ARN Neoplásico/biosíntesis , Retinoblastoma/metabolismo , Femenino , Humanos , Masculino , Invasividad Neoplásica , ARN Largo no Codificante/genética , ARN Neoplásico/genética , Retinoblastoma/genética , Retinoblastoma/mortalidad , Retinoblastoma/patologíaRESUMEN
Lead silicate glasses are fundamental materials to a microchannel plate (MCP), which is a two dimensional array of a microscopic channel charge particle multiplier. Hydrogen reduction is the core stage to determine the electrical conductivity of lead silicate glass MCP multipliers. The nanoscale morphologies and microscopic potential distributions of silicate glass at different reduction temperatures were investigated via atomic force microscope (AFM) and Kelvin force microscopy (KFM). We found that the bulk resistance of MCPs ballooned exponentially with the spacing of conducting islands. Moreover, bulk resistance and the spacing of conducting islands both have the BiDoseResp trend dependence on the hydrogen reduction temperature. Elements composition and valence states of lead silicate glass were characterized by X-ray photoelectron spectroscopy (XPS). The results indicated that the conducting island was an assemblage of the Pb atom originated from the reduction of Pb2+ and Pb4+. Thus, this showed the important influence of the hydrogen temperature and nanoscale morphological transformation on modulating the physical effects of MCPs, and opened up new possibilities to characterize the nanoscale electronic performance of multiphase silicate glass.
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F16 is a mitochondria-targeted, broad-spectrum anticancer agent in the pre-clinic cancer therapy. Here we developed two fluorescent isomers of F16 (o-F16 and m-F16) with entirely different photophysical properties, uncoupling activity, and cytotoxicity by merely modifying the linking orientation of pyridinium and indole units. Individually, o-F16 acted as a strong uncoupler to reduce the mitochondrial respiration efficiency, while m-F16 could hardly uncouple the mitochondrial respiration due to its poor proton dissociation capability. Owing to their intrinsic fluorescence, o-F16 and m-F16 could specifically image mitochondria in the green and red channel, respectively. This work could provide useful information for the development of uncouplers and design of mitochondrial-targeted drugs.
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Antineoplásicos/farmacología , Colorantes Fluorescentes/farmacología , Indoles/farmacología , Mitocondrias Hepáticas/efectos de los fármacos , Compuestos de Piridinio/farmacología , Animales , Antineoplásicos/síntesis química , Antineoplásicos/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Colorantes Fluorescentes/síntesis química , Colorantes Fluorescentes/química , Humanos , Indoles/síntesis química , Indoles/química , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Simulación de Dinámica Molecular , Estructura Molecular , Compuestos de Piridinio/síntesis química , Compuestos de Piridinio/química , Ratas , Ratas Wistar , Relación Estructura-ActividadRESUMEN
AIM: To explore whether killer cell immunoglobulin-like receptors (KIR) gene polymorphisms are associated with susceptibility to persistent hepatitis B virus (HBV) infection or HBV clearance. METHODS: Fifteen known KIR genes were determined in 150 chronic hepatitis B patients, 251 spontaneously recovered controls, and 412 healthy controls by the sequence specific primer polymerase chain reaction (SSP-PCR) method. KIR genotype frequency (gf) differences were tested for significance by two-tailed Fisher exact test or chi(2) test. Multifactorial analysis was also performed by logistic analysis (the SAS system). RESULTS: Framework genes KIR2DL4, KIR3DL2, KIR3DL3, and KIRZ were present in all individuals. The frequencies of KIR2DS2 and KIR2DS3 were higher in chronic hepatitis B patients, than in both healthy and spontaneously recovered controls. The frequencies of activating KIR2DS1, KIR3DS1, and the inhibitory KIR2DL5 were higher in spontaneously recovered controls than in chronic hepatitis B patients and healthy controls. CONCLUSION: KIR polymorphisms may be associated with susceptibility to HBV infection or HBV clearance. It could be suggested that KIR2DS2 and KIR2DS3 were HBV-susceptive genes, which induced a persistent yet weak inflammatory reaction that resulted in continuous injury of live tissues and chronic hepatitis. KIR2DS1, KIR3DS1, and KIR2DL5, on the other hand, may be protective genes that facilitated the clearance of HBV.
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Pueblo Asiatico/genética , Predisposición Genética a la Enfermedad , Hepatitis B Crónica/genética , Polimorfismo Genético , Receptores Inmunológicos/genética , Estudios de Casos y Controles , Estudios de Cohortes , Frecuencia de los Genes , Hepatitis B Crónica/etnología , Humanos , Reacción en Cadena de la Polimerasa , Receptores KIR2DL4 , Receptores KIR2DL5 , Receptores KIR3DL2 , Receptores KIR3DS1RESUMEN
@#AIM:To analyze the efficacy and safety of pterygium resection respectively combined with Ologen collagen matrix implantation and autologous conjunctival flap transplantation.METHODS:A total of 80 patients(87 eyes)with pterygium admitted to the hospital between January 2017 and January 2020 were selected, and randomly divided into observation group(40 patients, 44 eyes)treated with pterygium resection combined with Ologen collagen matrix implantation and control group(40 patients, 43 eyes)treated with pterygium resection combined with autologous conjunctival flap transplantation. The patients were followed up till 12mo after operation. The best corrected visual acuity, corneal astigmatism, surface asymmetry index(SAI), surface regularity index(SRI), corneal epithelial healing, pterygium recurrence and the incidence of complications were compared between the two groups. RESULTS:Visual changes of the two groups were similar at 6 and 12mo after operation(<i>P</i>>0.05). Corneal astigmatism, SAI and SRI were reduced in the two groups at 1 and 3mo after operation. The corneal astigmatismat 3mo after operation and SAI, SRI at 1 and 3mo after operation were significantly lower in the observation group than in the control group(all <i>P</i><0.05). The corneal epithelial healing rate in observation group at 1wk after operation was significantly higher than that in the control group(73% <i>vs</i> 46%, <i>P</i><0.05), and corneal epithelium of the two groups healed at 2wk after operation. No pterygium recurrence was observed in the two groups within 12mo after operation. The situation of pterygium recurrence was similar in the two groups at 6 and 12mo after operation(<i>P</i>>0.05). There was no significant difference in the incidence of complications between the two groups(7% <i>vs </i>14%, <i>P</i>>0.05).CONCLUSION:Both pterygium resection combined with Ologen collagen matrix implantation and pterygium resection combined with autologous conjunctival flap transplantation are effective in the treatment of pterygium, with equivalent safety. However, the former has more advantages in improving corneal astigmatism and regular shape of corneal wound.
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To observe the curative effect of treating small -incision cataract extraction by intraocular lens implantation combined with trabeculectomy for primary angle-closure glaucoma with cataract. ●METHODS: Totally 44 cases (52 eyes) of primary angle-closure glaucoma combined with cataract were selected to undergo the combined surgery, in order to observe the patients' pre - and postoperative eyesights, intraocular pressures and the postoperative complications. ●RESULTS: The postoperative eyesight was improved significantly as compared with the preoperative eyesight. The intraocular pressure was declined dramatically. The result was of statistical significance (P ● CONCLUSlON: Treating the primary angle - closure glaucoma combined with cataract through the combined surgery has high reliability and desirable curative effect. The surgical method is simple to learn and applicable for promotion on the basic level.
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To clone human interleukin-26 (hIL-26) and express it in E. coli efficiently. Two pairs of primers were synthesized according to the hIL-26 gene reported on GenBank. The hIL-26 gene was cloned by nest PCR following the first round RT-PCR from human peripherial blood monocytes total RNA, and then the PCR product was cloned into pMD18-T vector. Colony PCR, restriction analysis and sequence analysis showed that the gene cloned was the same as the reported hIL-26. The recombinant was cut with BamHI and EcoR I to obtain the hIL-26 fragment, and then the fragment was inserted into pBV220 which was cut with the same enzymes. The recombinant expression vector was induced to express hIL-26 at 42 degrees C, SDS-PAGE analysis showed that the recombinant protein accounted for up to 20% of the whole protein of E. coli, and the protein was also confirmed by Western blotting. Purity of the protein was found to be above 90% after purified with molecular sieve. After renaturalized with glutathione buffer, the promoting effect of it on the production of IFN-y in PBMC was detected by RT-PCR. A recombinant bacterial strain for expressing hIL-26 with biological activity was constructed successfully.
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Humanos , Clonación Molecular , Escherichia coli , Genética , Metabolismo , Interleucinas , Genética , Proteínas Recombinantes , Genética , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Objective To assess and compare the difference in image quality and exposure dose between single-sided reading image plate(IP)and dual-sided reading IP.Methods A contrast-detail phantom CDRAD 2.0 was exposed by single-sided and dual-sided reading IP with different mAs sets.The entrance surface doses were recorded for all images.Images were then presented to two radiologists on a high resolution monitor of diagnosis workstation.The image quality figure(IQF)was measured for each image. Statistical analysis was performed using Spearman's correlation test and Wilcoxon signed-rank test to compare the difference in image quality and exposure dose between single-sided IP and dual-sided reading IP. Results With different tube current dosage of 5.6,12.0,20.0,25.0,and 40.0 mAs,IQF values of single-sided reading IP were 47.95,37.68,34.31,28.61,and 24.65,respectively,while those of dual- sided reading IP were 38.83,29.81,29.65,25.16,and 21.43,respectively.The IQF difference between them showed statistical significance(P
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Objective To explore whether autoreactive antibody presents in patients with sporadic idiopathic hypoparathyroidism(sIHP).Methods The subjects including 26 patients with sIHP and 112 genealogical members as well as 60 age-and sex-matched healthy controls.Anti-parathyroid antibodies in the sera were assayed by indirect immunofluorescence.The levels of calcium,phosphorus and magnesium as well as intact parathyroid hormone(iPTH)in the sera were tested.Results Positive autoantibodies against parathyroid tissue were demonstrated in 10 patients(38%)with sIHP,significantly higher than that of in genealogical members(10%,?~2=13.42,P