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Glycosylation is a valuable tool for modulating protein solubility; however, the lack of reliable research strategies has impeded efficient progress in understanding and applying this modification. This study aimed to bridge this gap by investigating the solubility of a model glycoprotein molecule, the carbohydrate-binding module (CBM), through a two-stage process. In the first stage, an approach involving chemical synthesis, comparative analysis, and molecular dynamics simulations of a library of glycoforms was employed to elucidate the effect of different glycosylation patterns on solubility and the key factors responsible for the effect. In the second stage, a predictive mathematical formula, innovatively harnessing machine learning algorithms, was derived to relate solubility to the identified key factors and accurately predict the solubility of the newly designed glycoforms. Demonstrating feasibility and effectiveness, this two-stage approach offers a valuable strategy for advancing glycosylation research, especially for the discovery of glycoforms with increased solubility.
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Aprendizaje Automático , Simulación de Dinámica Molecular , Solubilidad , Glicosilación , Glicoproteínas/químicaRESUMEN
Under high relative humidity (RH) conditions, the release of volatile components (such as acetate) has a significant impact on the aerosol hygroscopicity. In this work, one surface plasmon resonance microscopy (SPRM) measurement system was introduced to determine the hygroscopic growth factors (GFs) of three acetate aerosols separately or mixed with glucose at different RHs. For Ca(CH3COO)2 or Mg(CH3COO)2 aerosols, the hygroscopic growth trend of each time was lower than that of the previous time in three cyclic humidification from 70% RH to 90% RH, which may be due to the volatility of acetic acid leading to the formation of insoluble hydroxide (Ca(OH)2 or Mg(OH)2) under high RH conditions. Then the third calculated GF (using the Zdanovskii-Stokes-Robinson method) for Ca(CH3COO)2 or Mg(CH3COO)2 in bicomponent aerosols with 1:1 mass ratio were 3.20% or 5.33% lower than that of the first calculated GF at 90% RH. The calculated results also showed that the hygroscopicity change of bicomponent aerosol was negatively correlated with glucose content, especially when the mass ratio of Mg(CH3COO)2 to glucose was 1:2, the GF at 90% RH only decreased by 4.67% after three cyclic humidification. Inductively coupled plasma atomic emission spectrum (ICP-AES) based measurements also indicated that the changes of Mg2+concentration in bicomponent was lower than that of the single-component. The results of this study reveal thatduring the efflorescence transitions of atmospheric nanoparticles, the organic acids diffusion rate may be inhibited by the coating effect of neutral organic components, and the particles aging cycle will be prolonged.
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Microscopía , Resonancia por Plasmón de Superficie , Humectabilidad , Aerosoles , Acetatos , GlucosaRESUMEN
BACKGROUND: Gut microbiome is critical to our human health and is related to postmenopausal osteoporosis (PMO). Strontium ranelate (SrR) is an anti-osteoporosis oral drug that can promote osteoblast formation and inhibit osteoclast formation. However, the effect of SrR on gut microbiome has been rarely studied. Therefore, we investigated the effect of oral SrR on gut microbiome and metabolic profiles. RESULTS: In this study, we used ovariectomized (OVX) Sprague-Dawley rats to construct a PMO model and applied oral SrR for 6 weeks. The relative abundance of intestinal microbiome was investigated by 16S rRNA metagenomic sequencing. Ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) was used to analyze changes in metabolites of intestinal contents. Results demonstrated that 6-week oral SrR alleviated osteoporosis and significantly changed the composition of the gut microbiome and metabolic profiles of OVX rats. Ruminococcus, Akkermansia and Oscillospira were significantly enriched in the gut of OVX rats after 6-week oral SrR. Especially, the species R. albus showed the greatest importance by a random forest classifier between OVX and OVX_Sr group. The enrichment of R. albus in the gut was positively correlated with bone mineral density and the accumulation of lycopene and glutaric acid, which also significantly elevated after oral SrR. CONCLUSIONS: We discovered that oral SrR can improve bone health while stimulate the accumulation of gut microbe R. albus and metabolites (lycopene and glutaric acid). The results suggested possible connections between oral SrR and the gut-bone axis, which may provide new insight into the treatment/prevention of osteoporosis.
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Microbioma Gastrointestinal , Osteoporosis Posmenopáusica , Osteoporosis , Humanos , Femenino , Ratas , Animales , Ratas Sprague-Dawley , Osteoporosis Posmenopáusica/tratamiento farmacológico , Osteoporosis Posmenopáusica/metabolismo , Ruminococcus , Licopeno/uso terapéutico , ARN Ribosómico 16S/genética , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismoRESUMEN
Dissolved oxygen (DO) in water bodies is a prerequisite for fish survival and plays a crucial role in fish growth, development, and physiological processes. However, with increasing eutrophication, greenhouse effects, and extreme weather conditions, DO levels in aquatic environments often become lower than normal. This leads to stress in fish, causing them to exhibit escape behavior, inhibits their growth and development, and causes tissue damage. Moreover, oxidative stress, decreased immune function, and altered metabolism have been observed. Severe hypoxia can cause massive fish mortality, resulting in significant economic losses to the aquaculture industry. In response to hypoxia, fish exhibit a series of behavioral and physiological changes that are self-protective mechanisms formed through long-term evolution. This review summarizes the effects of hypoxic stress on fish, including the asphyxiation point, behavior, growth and reproduction, tissue structure, physiological and biochemical processes, and regulation of gene expression. Furthermore, future research directions are discussed to provide new insights and references.
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When exposed to different relative humidities (RHs), the optical properties of atmospheric aerosols will change because of changes in the aerosol particle size and complex refractive index (RI), which will affect haze formation and global climate change. The potential contributions of ultrafine particles to the atmospheric optical characteristics and to haze spreading cannot be ignored because of their high particle number concentrations and strong diffusibility; measurement of the optical properties of wet ultrafine particles is thus highly important for environmental assessment. Therefore, a surface plasmon resonance microscopy with azimuthal rotation illumination (SPRM-ARI) system is designed to determine the RIs of single particle aerosols with diameters of less than 100 nm in the hygroscopic growth process. Measurements are taken using mixed single particles with different mass ratios. The RIs of mixed single aerosols at different RHs are retrieved by measuring the scattering light intensity using the SPRM-ARI system and almost all the RIs of the bicomponent particles with different mass ratios decrease with increasing water content under high RH conditions. Finally, for each of the bicomponent particles, the maximum standard deviations for the retrieved RI values are only 2.06×10-3, 3.08×10-3 and 3.83×10-3, corresponding to the NaCl and NaNO3 bicomponent particles with a 3:1 mass ratio at 76.0% RH, the NaCl and glucose particles with a 1:3 mass ratio at 89.0% RH, and the NaCl and OA particles with a 1:1 mass ratio at 78.0% RH, respectively; these results indicate that the high-sensitivity SPRM-ARI system can measure the RI effectively and accurately.
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Refractometría , Resonancia por Plasmón de Superficie , Microscopía , Material Particulado , Péptidos y Proteínas de Señalización Intercelular , BismutoRESUMEN
A thorough understanding of chemical composition, particle pH, and pollutant emissions is essential to address the climate and human health effects of atmospheric particles. In this study, we used a High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) and Scanning Mobility Particle Sizer (SMPS) to characterize the composition of submicron particles. Moreover, we applied the ISORROPIA-II model to analyze the particle acidity effect on the compositional characterization of submicron particles from December 22, 2016 to January 7, 2017 in Albany, New York, USA. The results indicated that aerosols with mobility diameter from SMPS in the range 200-400 nm were the main contributors to the mass during the measurement period. The dominance of organics (47%) and sulfate (16%) was similar to previous observations in the eastern United States in Winter 2015, while the fraction of nitrate (23%) was much higher. Moreover, nitrate could easily form at colder temperatures and lower RH levels even when there were more acidic particle periods during the measurement period in Albany. The ISORROPIA-II model indicated that there were more acidic particles, which was estimated using pH values. Lower temperature conditions tended to favor nitrate formation. The nitrate concentration exceeded that of sulfate in the measurement period, even though the SO2 and NOx emissions were similar. The organics in submicron particles were strongly influenced by the local emissions in winter. However, the inorganic compounds in submicron particles could be derived from regional transport as their pollution sources originated from different directions. This may help strategize emission reductions in the future.
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Contaminantes Atmosféricos , Material Particulado , Aerosoles/análisis , Contaminantes Atmosféricos/análisis , Monitoreo del Ambiente , Humanos , New York , Tamaño de la Partícula , Material Particulado/análisisRESUMEN
From the beginning of 2002 and 2012, severe respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) crossed the species barriers to infect humans, causing thousands of infections and hundreds of deaths, respectively. Currently, a novel coronavirus (SARS-CoV-2), which has become the cause of the outbreak of Coronavirus Disease 2019 (COVID-19), was discovered. Until 18 February 2020, there were 72 533 confirmed COVID-19 cases (including 10 644 severe cases) and 1872 deaths in China. SARS-CoV-2 is spreading among the public and causing substantial burden due to its human-to-human transmission. However, the intermediate host of SARS-CoV-2 is still unclear. Finding the possible intermediate host of SARS-CoV-2 is imperative to prevent further spread of the epidemic. In this study, we used systematic comparison and analysis to predict the interaction between the receptor-binding domain (RBD) of coronavirus spike protein and the host receptor, angiotensin-converting enzyme 2 (ACE2). The interaction between the key amino acids of S protein RBD and ACE2 indicated that, other than pangolins and snakes, as previously suggested, turtles (Chrysemys picta bellii, Chelonia mydas, and Pelodiscus sinensis) may act as the potential intermediate hosts transmitting SARS-CoV-2 to humans.
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Betacoronavirus/genética , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/transmisión , Pandemias , Peptidil-Dipeptidasa A/química , Neumonía Viral/epidemiología , Neumonía Viral/transmisión , Receptores Virales/química , Glicoproteína de la Espiga del Coronavirus/química , Secuencia de Aminoácidos , Enzima Convertidora de Angiotensina 2 , Animales , Betacoronavirus/clasificación , Betacoronavirus/patogenicidad , Sitios de Unión , COVID-19 , China/epidemiología , Quirópteros/virología , Infecciones por Coronavirus/virología , Euterios/virología , Humanos , Modelos Moleculares , Peptidil-Dipeptidasa A/genética , Peptidil-Dipeptidasa A/metabolismo , Filogenia , Neumonía Viral/virología , Unión Proteica , Conformación Proteica en Hélice alfa , Conformación Proteica en Lámina beta , Dominios y Motivos de Interacción de Proteínas , Mapeo de Interacción de Proteínas , Receptores Virales/genética , Receptores Virales/metabolismo , SARS-CoV-2 , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Serpientes/virología , Glicoproteína de la Espiga del Coronavirus/clasificación , Glicoproteína de la Espiga del Coronavirus/genética , Glicoproteína de la Espiga del Coronavirus/metabolismo , Tortugas/virologíaRESUMEN
In order to realize accurate dynamic control of supersaturation and to study condensation growth characteristics of nanoparticles through different levels of supersaturation, a series of parametric analyses and systematic comparisons between two-stage and three-stage operating temperature designs were simulated with COMSOL Multiphysics. The simulation results showed that the three-stage operating temperature did not change peak supersaturation compared with two operating temperatures, and the three-stage operating temperature was superior in decreasing the amount of water vapor and the temperature, thus lowering particle loss and variation in detection and collection. The peak supersaturation level increased by 0.3 as the flow rate increased from 0.6 to 2.0 L/min, but the supersaturation peak moved from 0.0027 z0 to 0.08 z0 (i.e., the growth time and the final size decreased by 40%). Peak supersaturation increased as the temperature difference increased or the temperature difference window was shifting left, and minimum activation size decreased. Shifting the 70°C temperature difference window from 9°C, 79°C-1°C, 71°C for the condenser and initiator temperatures resulted in peak supersaturation in the centerline being above 5.8, and the activation size changed as low as 1 nm. Experiments with flow rates varying by a factor of 2.5 (from 0.6 to 1.5 L/min) resulted in a final size decrease of 43% (from 3.2 to 1.8 µm), and experimental results of outlet particle size distributions were equivalent with theoretical analysis as the operating temperature was changed.
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Modelos Químicos , Nanopartículas/química , Temperatura , AguaRESUMEN
The subunits PA, PB1, and PB2 of influenza A virus RNA polymerase are essential for efficient viral RNA synthesis and virus replication because of their role in recruiting multiple nuclear proteins. ANP32A is an acidic leucine-rich nuclear phosphoprotein 32 (ANP32) family member and a crucial cellular protein that determines the species specificity of the influenza virus RNA polymerase activity. However, how ANP32A modulates polymerase activity remains largely unknown. In this study, we showed that viral RNA synthesis was increased in A549 cells overexpressing ANP32A and decreased after treatment with ANP32A RNAi. This decrease in RNA synthesis was reversed by rescued ANP32A expression. The results of docking modeling, co-immunoprecipitation, and yeast two-hybrid assays showed that PB2 was the only subunit of the three that interacted with ANP32A. The C-terminal portion of ANP32A and the middle domains (residues 307-534) of PB2 were required for PB2-ANP32A interaction. Glu189 and Glu196 in ANP32A and Gly450 and Gln447 in PB2 were essential for interaction between ANP32A and PB2. These residues were located in conserved regions of the ANP32A or PB2 protein sequences. These data suggest that ANP32A is recruited to the polymerase through direct interaction with PB2 via critical amino acid residue interactions and promotes viral RNA synthesis. Our findings might provide new insights into the molecular mechanisms underlying influenza virus RNA synthesis and replication in infected human cells.
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Subtipo H1N1 del Virus de la Influenza A/enzimología , Gripe Humana/metabolismo , Gripe Humana/virología , Péptidos y Proteínas de Señalización Intracelular/metabolismo , ARN Viral/genética , ARN Polimerasa Dependiente del ARN/metabolismo , Proteínas Virales/metabolismo , Secuencias de Aminoácidos , Interacciones Huésped-Patógeno , Humanos , Subtipo H1N1 del Virus de la Influenza A/química , Subtipo H1N1 del Virus de la Influenza A/genética , Gripe Humana/genética , Péptidos y Proteínas de Señalización Intracelular/química , Péptidos y Proteínas de Señalización Intracelular/genética , Simulación del Acoplamiento Molecular , Proteínas Nucleares , Unión Proteica , ARN Viral/metabolismo , Proteínas de Unión al ARN , ARN Polimerasa Dependiente del ARN/química , ARN Polimerasa Dependiente del ARN/genética , Proteínas Virales/química , Proteínas Virales/genéticaRESUMEN
Many human proteins have the potential to be developed as therapeutic agents. However, side effects caused by direct administration of natural proteins have significantly slowed expansion of protein therapeutics into the clinic. Post-translational modifications (PTMs) can improve protein properties, but because of significant knowledge gaps, we are considerably limited in our ability to apply PTMs to generate better protein therapeutics. Here, we seek to fill the gaps by studying the PTMs of a small representative chemotactic cytokine, RANTES. RANTES can inhibit HIV-1 infection by competing with it for binding to receptor CCR5 and stimulating CCR5 endocytosis. Unfortunately, RANTES can induce strong signaling, leading to severe inflammatory side effects. We apply a chemical biology approach to explore the potential of post-translationally modified RANTES as safe inhibitors of HIV-1 infection. We synthesized and systematically tested a library of RANTES isoforms for their ability to inhibit inflammatory signaling and prevent HIV-1 infection of primary human cells. Through this research, we revealed that most of the glycosylated variants have decreased inflammation-associated properties and identified one particular glyco variant, a truncated RANTES containing a Galß1-3GalNAc disaccharide α-linked to Ser4, which stands out as having the best overall properties: relatively high HIV-1 inhibition potency but also weak inflammatory properties. Moreover, our results provided a structural basis for the observed changes in the properties of RANTES. Taken together, this work highlights the potential importance of glycosylation as an alternative strategy for developing CCR5 inhibitors to treat HIV-1 infection and, more generally, for reducing or eliminating unwanted properties of therapeutic proteins.
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Quimiocina CCL5/química , Quimiocina CCL5/farmacología , Inhibidores de Fusión de VIH/química , Inhibidores de Fusión de VIH/farmacología , VIH-1/efectos de los fármacos , Procesamiento Proteico-Postraduccional , Acilación , Biopolímeros , Espectroscopía de Resonancia Magnética con Carbono-13 , Quimiocina CCL5/efectos adversos , Quimiocina CCL5/metabolismo , Quimiotaxis de Leucocito/efectos de los fármacos , Glicosaminoglicanos/metabolismo , Glicosilación , Inhibidores de Fusión de VIH/efectos adversos , Inhibidores de Fusión de VIH/metabolismo , Infecciones por VIH/tratamiento farmacológico , VIH-1/fisiología , Humanos , Espectroscopía de Protones por Resonancia Magnética , Receptores CCR5/metabolismo , Células THP-1RESUMEN
Radiation-induced lung injury (RILI) is the main complication of radiotherapy for thoracic malignancies. Since naringenin, a potent immune-modulator, has been found to relieve bleomycin-induced lung fibrosis by restoring the balance of disordered cytokines, we sought to determine whether naringenin would mitigate RILI and to investigate the underlying mechanism. Animals received fractionated irradiation in the thoracic area to induce RILI. Enzyme-linked immunosorbent assay and MILLIPLEX assays were used for serum and bronchoalveolar lavage fluid for cytokine analyses, hematoxylin and eosin staining for pathologic changes, and Masson trichrome staining for determination of lung fibrosis. Interleukin (IL)-1ß was found significantly elevated after thoracic irradiation and it triggered production of profibrotic tumor growth factor ß both in vivo and in vitro, suggesting the vital role of in IL-1ß in the development of RILI. Furthermore, we found that naringenin was able to ameliorate RILI through downregulation of IL-1ß and restoration of the homeostasis of inflammatory factors. Our results demonstrated that naringenin could serve as a potent immune-modulator to ameliorate RILI. More importantly, we suggest that a new complementary strategy of maintaining the homeostasis of inflammatory factors combined with radiation could improve the efficacy of thoracic radiotherapy.
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Flavanonas/farmacología , Interleucina-1beta/metabolismo , Lesión Pulmonar/tratamiento farmacológico , Lesión Pulmonar/metabolismo , Traumatismos Experimentales por Radiación/tratamiento farmacológico , Traumatismos Experimentales por Radiación/metabolismo , Animales , Femenino , Flavanonas/uso terapéutico , Homeostasis/efectos de los fármacos , Mediadores de Inflamación/metabolismo , Ratones , Ratones Endogámicos C57BLRESUMEN
BACKGROUND: A combination of quantitative marinating and Maillard reaction was investigated by adding d-xylose, l-cysteine and thiamine to the marinated brine of quantitative marinating, which was expected to enhance the volatile flavor of Chinese marinated chicken. Response surface methodology was used to optimize parameters, in which response was sensory evaluation scores of marinated chicken. A Box-Behnken center design was applied to the optimized added contents. The optimized contents were d-xylose (1-5), l-cysteine (1-5) and thiamine (1-3). RESULTS: Analysis of variance indicated that a second-order polynomial equation could predict the experimental data well (R2 = 0.94), and sensory evaluation scores were significantly affected by the added amount of d-xylose, l-cysteine and thiamine. The optimal conditions that maximized the sensory evaluation score of Chinese marinated chicken were found to be 4.96 d-xylose, 2.28 l-cysteine and 2.66 thiamine (w/w). Given these optimal conditions, a number of meat-like flavor compounds such as 2-pentyl-furan, benzothiazole and 4-methyl-5-thiazoleethanol were identified by gas chromatographic-mass spectrometric analysis. CONCLUSION: Our results suggested that a combination of quantitative marinating and Maillard reaction might be a promising method to enhance the volatile flavor, especially meat-like flavor, of Chinese marinated chicken. © 2016 Society of Chemical Industry.
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Condimentos/análisis , Aromatizantes/química , Calidad de los Alimentos , Carne/análisis , Compuestos Orgánicos Volátiles/análisis , Animales , Beijing , Benzotiazoles/análisis , Benzotiazoles/química , Pollos , Cisteína/química , Furanos/análisis , Furanos/química , Humanos , Reacción de Maillard , Estructura Molecular , Sales (Química)/química , Sensación , Estadística como Asunto , Gusto , Tiamina/química , Tiazoles/análisis , Tiazoles/química , Compuestos Orgánicos Volátiles/química , Xilosa/químicaRESUMEN
UNLABELLED: Odor pollution is a big environmental problem caused by large-scale livestock production in China, and developing a practical way to reduce these odors is pressing. In this study, a combination of 0.2-1.0 U/mL lignin peroxidase (LiP) and one of three peroxides (H2O2, CaO2, 2Na3CO3·3H2O2) was examined for its efficiency in reducing the release of eight chemicals (propionic acid, isobutyric acid, isocaproic acid, isovaleric acid, phenol, p-cresol, indole, and skatole), NH3, H2S, and odor intensity from pig manure. The results showed an approximately 90% reduction in p-cresol, 40-60% reduction in odor intensity, 16.5-40% reduction in indolic compounds, and 25-40% reduction in volatile fatty acids. Being the electron acceptors of LiP, 2Na3CO3·3H2O2 and CaO2 performed better than H2O2 in reducing the concentration of eight chemicals, NH3, H2S, and odor intensity from pig manure. The effect of deodorization can last for up to 72 hr. IMPLICATIONS: In China, one of the major environmental problems caused by confined feeding is odor pollution, which brings a major threat to the sustainability, profitability, and growth of the livestock industry. To couple the LiP with the electron acceptors, a low-cost, simple, and feasible method for odor removal was established in this study. Based on the study results, a practical treatment method was provided for odor pollution and supply the farm operators a more flexible time to dispose treated manure.
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Estiércol , Odorantes/prevención & control , Peroxidasas/metabolismo , Peróxidos/metabolismo , Animales , PorcinosRESUMEN
A method of fast nondestructive determination of three kinds of water-soluble inorganic ions including SO4²â», NO3â» NH4⺠in aerosol was disscussed. The method of IC measurement values was used on the control of the three kinds of inorganic ion content. The quantitative calibration models of the inorganic ions were developed by using ATR-FTIR spectroscopy combined with PLS algorithm and the model was evaluated. Markov distance discriminant method was used to identify and eliminate outliers, different mathematical treatments for spectra processing and different wavelength ranges were compared to determine the best model and the optimal model parameters was determined. The results showed that second derivative analysis after eliminating outliers can improve the prediction, PLS analysis can get better results for SO4²â» in the range of 1220-900 cm⻹, for NO3â» in the range of 1521-900 cm⻹ and for NH in the range of 1521-1220 cm⻹, the RMSEP were 1.736 7, 1.023 9 and 1.482 3, respectively. The foundation of real-time fast quantitative analysis of the three kinds of inorganic ion in a large number of aerosol samples was established.
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The four kinds of the structure characteristics of rotary type interferometer are mainly analyzed from the classical Michelson interferometer structure in the paper. The Optical path difference between the interferometer and the rotation angle is also analyzed. By setting parameters, the four kinds of rotary type optical path difference of the interferometer are simulated based on the optical path difference formula. The rotation velcocity of the four kinds of interferometers is also simulated. By simulation and contrast of the optical path difference, the relationship is intuitively reflect by figure between the optical path difference and the rotation angle. The scope of the rotation angle is discussed within 3% of the velocity errors. It is the very good reference significance to study the structure and properties of the interferometer by analyzing and simulating the optical path difference discussed in the paper.
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We developed a rehabilitation system by using the virtual reality technique and the Kinect in this paper. The system combines rehabilitation training with HMI and serious game organically, and provides a game and motion database to meet different patients' demands. Extended interface of game database is provided in two ways: personalized games can be developed by Virtools and Flash games which are suitable for patients' rehabilitation can be download from the Internet directly. In addition, the system provides patients with flexible interaction and easy control mode, and also presents real time data recording. An objective and subjective evaluation method is proposed to review the effectiveness of the rehabilitation training. According to the results of short questionnaires and the evaluation results of patients' rehabilitation training, the system compared with traditional rehabilitation can record and analyze the training data, which is useful to make rehabilitation plans. More entertainment and lower cost will increase patients' motivation, which helps to increase the rehabilitation effectiveness.
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Rehabilitación/métodos , Extremidad Superior/fisiopatología , Interfaz Usuario-Computador , Simulación por Computador , Humanos , Internet , Rehabilitación/instrumentación , Juegos de VideoRESUMEN
Proteolytic enzymes in the gut represent one of the biggest barriers against oral delivery of therapeutic proteins and peptides. In the current study, we explored the effect of poly(ethylene glycol) 400 (PEG 400), a commonly used crowding agent, on insulin degradation mediated by α-chymotrypsin (α-CT). Without PEG 400, insulin was quickly cleaved by α-CT to generate inactive degradation products. In comparison, incorporation of PEG 400 resulted in reaction mixtures with retained biological activity. The analysis on the conformation of α-CT and the local environment of the enzyme's active site unraveled that PEG 400 altered the conformation of α-CT to prevent the inactivation of insulin via stabilization of active intermediates. These findings indicated that PEG 400 may provide a promising addition toward oral delivery of insulin.
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Quimotripsina/química , Insulina/metabolismo , Polietilenglicoles/química , Animales , Cromatografía Líquida de Alta Presión , Dicroismo Circular , Conformación Proteica , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción , PorcinosRESUMEN
In order to observe two kinds of greenhouse gases, CO2 and CH4, making the biggest contribution to global warming, a ground-based Fourier transform near-infrared spectral remote sensing system was developed to record the perpendicular incidence sun spectra from February 2012 to April 2013 in Hefei continuously. The measured total transmittances in the atmosphere were obtained from perpendicular incidence sun spectra. Methods of line-by-line and low-order polynomial approximation were used to model the total atmospheric transmittances in forward model. The measured transmittance spectra were fitted iteratively using the modeled transmittance spectra in the regions of CO2 6,150-6,270 and CH4 5,970-6,170 cm(-1) in order to obtain their column concentrations. The column-average dry-air mole fractions of CO2 and CH4 were obtained with the internal standard function of O2 column concentrations. CO2 and CH4 daily average values of column-average dry-air mole fractions changed with a larger fluctuation and obvious seasonal periodicity. Their monthly average values were consistent as a whole, although there were different characteristics. Compared with the results reported by Japanese greenhouse-gas satellite in the area of Waliguan, there was a time lag corresponding to peak and trough of CO2 content and the change from peak to trough costed a longtime. CHR content showed variation tendency of unique peak and trough, higher in summer and lower in winter, compared with average values of nationwide CH4 column concentrations based on SCIAMACHY data. The variation characteristics were related to complex factors such as the balance of source and sink, meteorological and climate conditions, and required long-term observation and further study.
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is crucial for protecting vulnerable individuals, yet individuals with type 2 diabetes mellitus (T2DM) often exhibit impaired vaccine responses. Emerging evidence suggests that the composition of the host microbiota, crucial in immune regulation and development, influences vaccine efficacy. This study aimed to characterize the relationships between the SARS-CoV-2 inactivated vaccine and the host microbiota (specifically, gut and lung microbiota) of C57BL/6 mice with T2DM. Employing 16S rRNA metagenomic sequencing and ultra-high-performance liquid chromatography-mass spectrometry, we observed lower alpha diversity and distinct beta diversity in fecal microbiota before vaccination and in gut microbiota 28 days post-vaccination between T2DM mice and healthy mice. Compared with healthy mice, T2DM mice showed a higher Firmicutes/Bacteroidetes ratio 28 days post-vaccination. Significant alterations in gut microbiota composition were detected following vaccination, while lung microbiota remained unchanged. T2DM was associated with a diminished initial IgG antibody response against the spike protein, which subsequently normalized after 28 days. Notably, the initial IgG response positively correlated with fecal microbiota alpha diversity pre-vaccination. Furthermore, after 28 days, increased relative abundance of gut probiotics (Bifidobacterium and Lactobacillus) and higher levels of the gut bacterial tryptophan metabolite, indole acrylic acid, were positively associated with IgG levels. These findings suggest a potential link between vaccine efficacy and gut microbiota composition. Nonetheless, further research is warranted to elucidate the precise mechanisms underlying the impact of the gut microbiome on vaccine response. Overall, this study enhances our understanding of the intricate relationships among host microbiota, SARS-CoV-2 vaccination, and T2DM, with potential implications for improving vaccine efficacy. IMPORTANCE: Over 7 million deaths attributed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by 6 May 2024 underscore the urgent need for effective vaccination strategies. However, individuals with type 2 diabetes mellitus (T2DM) have been identified as particularly vulnerable and display compromised immune responses to vaccines. Concurrently, increasing evidence suggests that the composition and diversity of gut microbiota, crucial regulators of immune function, may influence the efficacy of vaccines. Against this backdrop, our study explores the complex interplay among SARS-CoV-2 inactivated vaccination, T2DM, and host microbiota. We discover that T2DM compromises the initial immune response to the SARS-CoV-2 inactivated vaccine, and this response is positively correlated with specific features of the gut microbiota, such as alpha diversity. We also demonstrate that the vaccination itself induces alterations in the composition and structure of the gut microbiota. These findings illuminate potential links between the gut microbiota and vaccine efficacy in individuals with T2DM, offering valuable insights that could enhance vaccine responses in this high-risk population.
Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Diabetes Mellitus Tipo 2 , Heces , Microbioma Gastrointestinal , Ratones Endogámicos C57BL , SARS-CoV-2 , Vacunas de Productos Inactivados , Animales , Ratones , Diabetes Mellitus Tipo 2/inmunología , Vacunas de Productos Inactivados/inmunología , COVID-19/prevención & control , COVID-19/inmunología , SARS-CoV-2/inmunología , Heces/microbiología , Vacunas contra la COVID-19/inmunología , Inmunoglobulina G/sangre , ARN Ribosómico 16S/genética , Pulmón/microbiología , Pulmón/inmunología , Femenino , Masculino , Probióticos/administración & dosificación , Anticuerpos Antivirales/sangre , Eficacia de las VacunasRESUMEN
To investigate the nutritional quality and flavor characteristics of Micropterus salmoides muscle cultivated in the pond (P), in-pond raceway (IPRS), and industrial aquaponics (ARAS) systems, we comprehensively analyzed texture properties, nutrient compositions, and volatile compounds. Our results revealed firmer flesh in P-cultured fish due to greater hardness and mastication. ARAS fish exhibited lower crude fat but higher crude protein and muscle glycogen. Notably, recirculating aquaculture significantly elevated total amino acids, minerals, and ΣPUFA/ΣSFA ratio, enhancing nutritional value. Pyrazine,2-methoxy-3-(2-methylpropyl)-, and ß-Ionone were identified as key flavor compounds. Volatile metabolites in all systems were dominated by woody, herbal, and sweet aroma profiles, with ARAS achieving the highest odor activity value, suggesting improved overall flavor. This study underscores the pivotal role of recirculating aquaculture in enhancing Micropterus salmoides quality, positioning it as a new quality productive force.