Selective delivery of interleukine-1 receptor antagonist to inflamed joint by albumin fusion

BACKGROUND: Interleukin-1 receptor antagonist, a cytokine that is highly therapeutic to rheumatoid arthritis and several other inflammatory diseases, exhibits rapid blood clearance and poor retention time on the target in clinical application due to its small size and lack of specificity to target tissue. Albumin has been widely employed as macromolecular carrier for drug delivery purpose to extend the plasma half-life of therapeutic molecules and has been shown to selectively accumulate and to be metabolized in the inflamed joints of patients with rheumatoid arthritis. This suggests that genetic fusion of IL-1ra to albumin can probably overcome the drawbacks of in vivo application of IL-1ra. RESULT: A recombinant protein, engineered by fusing human serum albumin (HSA) to the carboxyl terminal of IL-1ra, was produced in Pichia pastoris and purified to homogeneity. The fusion protein retained the antagonist activity of IL-1ra and had a plasma half-life of approximately 30-fold more than that of IL-1ra in healthy mice. In vivo bio-distribution studies demonstrated that the fusion protein selectively accumulated in arthritic paws for a long period of time in mice with collagen-induced arthritis, showing low uptake rates in normal organs such as liver, kidney, spleen and lung in contrast to IL-1ra alone. Moreover, this fusion protein was able to significantly improve the therapeutic efficacy of IL-1ra in collagen-induced arthritis mouse model. CONCLUSIONS: The fusion protein described here, able to selectively deliver IL-1ra to inflamed tissue, could yield important contributions for the therapy of rheumatoid arthritis and other inflammatory diseases

Characterising User Transfer Amid Industrial Resource Variation: A Bayesian Nonparametric Approach

In a multitude of industrial fields, a key objective entails optimising resource management whilst satisfying user requirements. Resource management by industrial practitioners can result in a passive transfer of user loads across resource providers, a phenomenon whose accurate characterisation is both challenging and crucial. This research reveals the existence of user clusters, which capture macro-level user transfer patterns amid resource variation. We then propose CLUSTER, an interpretable hierarchical Bayesian nonparametric model capable of automating cluster identification, and thereby predicting user transfer in response to resource variation. Furthermore, CLUSTER facilitates uncertainty quantification for further reliable decision-making. Our method enables privacy protection by functioning independently of personally identifiable information. Experiments with simulated and real-world data from the communications industry reveal a pronounced alignment between prediction results and empirical observations across a spectrum of resource management scenarios. This research establishes a solid groundwork for advancing resource management strategy development

Altered Gut Microbiota in Myasthenia Gravis

Myasthenia gravis (MG) is an autoimmune-mediated disorder, the etiology of which involves both environmental factors and genetics. While the exact factors responsible for predisposition to MG remain elusive, it is hypothesized that gut microbiota play a critical role in the pathogenesis of MG. This study investigated whether gut microbiota are altered in MG patients by comparing the fecal microbiota profiles of MG patients to those of age- and sex-matched healthy controls. Phylotype profiles of gut microbial populations were generated using hypervariable tag sequencing of the V4 region of the 16S ribosomal RNA gene. Fecal short-chain fatty acids (SCFAs) were assessed by gas chromatographic analyses. The results demonstrated that, compared to the healthy cohort, the gut microbiota of the MG group was changed in terms of the relative abundances of bacterial taxa, with sharply reduced microbial richness, particularly in the genus Clostridium. The fecal SCFA content was significantly lower in the MG group. Furthermore, microbial dysbiosis was closely related to the levels of inflammatory biomarkers in the sera of MG patients

Global Carbon Budget 2023

Accurate assessment of anthropogenic carbon dioxide (CO2) emissions and their redistribution among the atmosphere, ocean, and terrestrial biosphere in a changing climate is critical to better understand the global carbon cycle, support the development of climate policies, and project future climate change. Here we describe and synthesize data sets and methodology to quantify the five major components of the global carbon budget and their uncertainties. Fossil CO2 emissions (EFOS) are based on energy statistics and cement production data, while emissions from land-use change (ELUC), mainly deforestation, are based on land-use and land-use change data and bookkeeping models. Atmospheric CO2 concentration is measured directly, and its growth rate (GATM) is computed from the annual changes in concentration. The ocean CO2 sink (SOCEAN) is estimated with global ocean biogeochemistry models and observation-based f CO2 products. The terrestrial CO2 sink (SLAND) is estimated with dynamic global vegetation models. Additional lines of evidence on land and ocean sinks are provided by atmospheric inversions, atmospheric oxygen measurements, and Earth system models. The resulting carbon budget imbalance (BIM), the difference between the estimated total emissions and the estimated changes in the atmosphere, ocean, and terrestrial biosphere, is a measure of imperfect data and incomplete understanding of the contemporary carbon cycle. All uncertainties are reported as ±1σ. For the year 2022, EFOS increased by 0.9 % relative to 2021, with fossil emissions at 9.9 ± 0.5 Gt C yr−1 (10.2 ± 0.5 Gt C yr−1 when the cement carbonation sink is not included), and ELUC was 1.2 ± 0.7 Gt C yr−1, for a total anthropogenic CO2 emission (including the cement carbonation sink) of 11.1 ± 0.8 Gt C yr−1 (40.7±3.2 Gt CO2 yr−1). Also, for 2022, GATM was 4.6±0.2 Gt C yr−1 (2.18±0.1 ppm yr−1; ppm denotes parts per million), SOCEAN was 2.8 ± 0.4 Gt C yr−1, and SLAND was 3.8 ± 0.8 Gt C yr−1, with a BIM of −0.1 Gt C yr−1 (i.e. total estimated sources marginally too low or sinks marginally too high). The global atmospheric CO2 concentration averaged over 2022 reached 417.1 ± 0.1 ppm. Preliminary data for 2023 suggest an increase in EFOS relative to 2022 of +1.1 % (0.0 % to 2.1 %) globally and atmospheric CO2 concentration reaching 419.3 ppm, 51 % above the pre-industrial level (around 278 ppm in 1750). Overall, the mean of and trend in the components of the global carbon budget are consistently estimated over the period 1959–2022, with a near-zero overall budget imbalance, although discrepancies of up to around 1 Gt C yr−1 persist for the representation of annual to semi-decadal variability in CO2 fluxes. Comparison of estimates from multiple approaches and observations shows the following: (1) a persistent large uncertainty in the estimate of land-use changes emissions, (2) a low agreement between the different methods on the magnitude of the land CO2 flux in the northern extra-tropics, and (3) a discrepancy between the different methods on the strength of the ocean sink over the last decade. This living-data update documents changes in methods and data sets applied to this most recent global carbon budget as well as evolving community understanding of the global carbon cycle. The data presented in this work are available at https://doi.org/10.18160/GCP-2023 (Friedlingstein et al., 2023)

Entropy Generation for Negative Frictional Pressure Drop in Vertical Slug and Churn Flows

It is widely accepted that the frictional pressure drop is impossible to be negative for pipe flow. However, the negative frictional pressure drops were observed for some cases of two-phase slug and churn flows in pipes, challenging the general sense of thermodynamic irreversibility. In order to solve this puzzling problem, theoretical investigations were performed for the entropy generation in slug and churn flows. It is found that the frictional pressure drop along with a buoyancy-like term contributes to the entropy generation due to mechanical energy loss for steady, incompressible slug and churn flows in vertical and inclined pipes. Experiments were conducted in a vertical pipe with diameter as 0.04 m for slug and churn flows. Most of the experimental data obtained for frictional pressure drop are negative at high gas–liquid ratios from 100 to 10,000. Entropy generation rates were calculated from experimental data. The results show that the buoyancy-like term is positive and responsible for a major part of entropy generation rate while the frictional pressure drop is responsible for a little part of entropy generation rate, because of which the overall entropy generation due to mechanical energy loss is still positive even if the frictional pressure drop is negative in vertical slug and churn flows. It is clear that the negative frictional pressure drops observed in slug and churn flows are not against the thermodynamics irreversibility

A New Method to Experimentally Investigate Local Pressure Loss of Oil-Water Two-Phase Flow through Pore Throats

To investigate the resistance performance of pore throats in porous media, a new method was used to conduct experiments to indirectly measure the local pressure loss of single-phase water and oil- water two-phase flow through pore-throat structures. Four microchannels were designed and manufactured with MEMS technology. One of the four microchannels is a straight duct with no throat and each of the other three has one throat within the passage. By comparison of total pressure drops between the straight duct with no throat and the channel with a throat at the same flow rate, the local pressure loss over a pore- throat structure can be determined. In this paper, the pore-throat structure is defined as a combination of a contraction, an expansion and a throat to stimulate the pore throat in porous media. Experimental results show that local pressure loss, nonlinear with the flow rate, grows up with the decrease of throat size and the increase of oil volume fraction. Local loss coefficient, characterizing the local resistance performance of pore-throat structure, diminishes with the increase of Reynolds number. Reynolds number (in throat part) is in the range of 100-1100. A new empirical correlation of local loss coefficient is proposed for single-phase water and oil-water two-phase flow through pore-throat structure

Phytoplankton Community Investigation and Water Quality Assessment of M River in winter in Shijiazhuang City

An investigation of phytoplankton community and water quality for M River was conducted in December 2019.The results showed that 38 species of phytoplankton belonging to 6 phyla and 26 genera were collected. Among them, Bacillariophyta is the richest species, which accounted for 34.21%, followed by Cyanophyta with 26.32% and Chlorophyta with 28.95%. The density of phytoplankton was 63.0*106 inds/L which indicated as eutrophic water body. The highest density was Bacillariophyta, accounting for 51.03%. The Shannon-Wiener diversity index (H’) varied from 1.34 to 2.24, the Margalef Species diversity index (d) varied from 2.71 to 3.85, and the Pielou evenness index (J) varied from 0.38 to 0.67. According to the integrative analysis results of H’, d and J, M River water quality belongs to oligo-polluted, but individual sites belong to meso-polluted

Ionic Liquids: Efficient Media for the Lipase-Catalyzed Michael Addition

Recently, ionic liquids (ILs) have been regarded as ideal media for non-aqueous bio-catalysis. In this work, the synthesis of warfarin by the lipase-catalyzed Michael addition in IL media and the parameters that affected the warfarin yield were investigated. Experimental results demonstrated that the chemical structures of the ILs were a major factor for influencing the warfarin yield. The ILs containing the NTf2– anion were suitable reaction media due to the high chemical stability of this anion. The incorporation of the hydroxyl group on the IL cation significantly improved the lipase activity due to the H2O-mimicking property of this group. The lipase activity decreased by increasing the alkyl chain length on the IL cation due to the non-polar domain formation of the IL cation at the active site entrance of lipase. The ILs and lipase could be reused no less than five times without reduction in the warfarin yield

Study of Oil-Water Two-Phase Stratified Flow in Horizontal Fractures

The relative permeability of oil-water two-phase flow is an important parameter in fractured petroleum reservoirs. It is widely accepted that the sum of relative permeabilities is less than 1. In this study, a series of experiments have been conducted on six rectangular fractures for oil-water two-phase flows. Analytical investigations of the effects of flow rate, aspect ratio, and fracture size on the relative permeability of oil-water two-phase are analysed. Basic fluid flow equations are combined to develop a new analytical model for water-oil two-phase flow in a horizontal fracture. The simulation results predicted by this model are in good agreement with the experimental data. The relative permeability is a function of flow ratio, viscosity ratio, aspect ratio and saturation. It increases as aspect ratio increases if the fracture depths are the same, while it decreases as aspect ratio increases if the fracture widths are identical. Both experiment and model indicate that the sum of relative permeabilities of oil and water is greater than 1 in some cases, different from the accepted view

Test and Simulation Analysis of Soybean Seed Throwing Process

In order to analyze the effect of different factors on the bouncing and rolling distance of soybeans at the time of seed throwing, tests and discrete element method (DEM) are employed to analyze test soil and three representative soybean varieties. The parameters between soybean seed particles and soil particles are calibrated by means of a piling test and simulation. A seed throwing test apparatus is improved to analyze the effects of seed throwing height, soil plane inclination angle and collision orientation on the bouncing and rolling distance of soybean seeds. The effect of relative seed throwing speed on the bouncing and rolling distance of soybean seeds is analyzed using a computer vision seeding test bench. On this basis, the above-mentioned test procedure is simulated and compared with the test results. The results showed that the bouncing distance of the soybean seed particles was not significant. The rolling distance had a certain randomness when the seed throwing height was different. When the inclination of the soil plane became larger, the rolling distance increased. When the sphericity of the soybean seed particles was high, the effect of different collision orientations was not obvious. If the sphericity was low, the rolling distance was the shortest when colliding in the horizontal orientation and the longest when colliding in the vertical orientation. The larger the relative seed throwing speed, the larger the rolling distance of the soybean seed particles