Long-acting bulleyaconitine A microspheres via intra-articular delivery for multidimensional therapy of rheumatoid arthritis.

Bulleyaconitine A (BLA) is a promising candidate for treating rheumatoid arthritis (RA) with diverse pharmacological activities, including anti-inflammatory, analgesic and bone repair. Herein, the long-acting bulleyaconitine A microspheres (BLA-MS) were developed to treat RA comprehensively by forming drug reservoirs in joint cavities. The BLA-MS were prepared by emulsion/solvent evaporation method. The particle size and distribution were assessed by SEM. The crystalline state was investigated by DSC and PXRD. The drug loading (DL), encapsulation efficiency (EE) and cumulative release in vitro were determined by HPLC. The DL and EE were 23.93 ± 0.38 % and 95.73 ± 1.56 % respectively, and the cumulative release was up to 69 days with a stable release curve. The pharmacodynamic results in collagen induced arthritis (CIA) rats showed a noticeable reduction in paw thickness (5.66 ± 0.32 mm), and the decreasing expression level of PGE2, TNF-α and IL-6 which diminished the infiltration of inflammatory cells, thereby alleviating the progression of erosion and repairing the damaged bones (BV/TV (Bone Volume / Total Volume): 81.97 %, BS/BV (Bone Surface / Bone Volume): 6.08 mm-1). In conclusion, intra-articular injection of BLA-MS should have a promising application in the treatment of RA and may achieve clinical transformation in the future.

Role of digital economic development in environmental transition of renewable energy sector of China.

This research looks at how China's expanding digital economy influences the country's efforts to green its renewable energy sector. Regression tests, endogeneity tests, correlation analysis, and robustness analysis are used to investigate the relationship between digital economic development and environmental consequences in the renewable energy sector. The results of the research show a significant positive association between the expansion of the digital economy and the transition to a more sustainable energy model in the clean energy sector. Regression studies reveal that the growth of the digital economy is positively correlated with a number of environmental indicators, including the generation of renewable energy, energy efficiency, and the decrease of carbon emissions. Endogeneity analyses have shown a causal relationship between digitization and environmental benefits in the renewable energy sector. The adoption of different digital technologies is strongly correlated. Robustness study, which ensures the validity and reliability of the collected results, further supports the importance of digital economic development in driving the environmental transformation of the renewable energy sector. The study's findings have significant implications for public policy. Funding digital infrastructure, fostering partnerships between the public and private sectors, standardizing data formats and interoperability, strengthening cybersecurity safeguards, and developing pro-digital policies and regulations are all important steps that policymakers can take to promote the widespread adoption of digital technologies.

Application of regional citrate anticoagulation in patients at high risk of bleeding during intermittent hemodialysis: a prospective multicenter randomized controlled trial.

OBJECTIVES: Safe and effective anticoagulation is essential for hemodialysis patients who are at high risk of bleeding. The purpose of this trial is to evaluate the effectiveness and safety of two-stage regional citrate anticoagulation (RCA) combined with sequential anticoagulation and standard calcium-containing dialysate in intermittent hemodialysis (IHD) treatment. METHODS: Patients at high risk of bleeding who underwent IHD from September 2019 to May 2021 were prospectively enrolled in 13 blood purification centers of nephrology departments, and were randomly divided into RCA group and saline flushing group. In the RCA group, 0.04 g/mL sodium citrate was infused from the start of the dialysis line during blood draining and at the venous expansion chamber. The sodium citrate was stopped after 3 h of dialysis, which was changed to sequential dialysis without anticoagulant. The hazard ratios for coagulation were according to baseline. RESULTS: A total of 159 patients and 208 sessions were enrolled, including RCA group (80 patients, 110 sessions) and saline flushing group (79 patients, 98 sessions). The incidence of severe coagulation events of extracorporeal circulation in the RCA group was significantly lower than that in the saline flushing group (3.64% vs. 20.41%, P<0.001). The survival time of the filter pipeline in the RCA group was significantly longer than that in the saline flushing group ((238.34±9.33) min vs. (221.73±34.10) min, P<0.001). The urea clearance index (Kt/V) in the RCA group was similar to that in the saline flushing group with no statistically significant difference (1.12±0.34 vs. 1.08±0.34, P=0.41). CONCLUSIONS: Compared with saline flushing, the two-stage RCA combined with a sequential anticoagulation strategy significantly reduced extracorporeal circulation clotting events and prolonged the dialysis time without serious adverse events.

Levels of Serum sST2, MMP-3, and Gal-3 in Patients with Essential Hypertension and Their Correlation with Left Ventricular Hypertrophy.

Essential hypertension (EH) is a clinically frequent cardiovascular disease, with insidious onset, causing increased pressure load and neuroregulation disorders in patients. Long-term EH can cause left ventricular hypertrophy (LVH), which can lead to arrhythmia and even death. The soluble suppression of tumorigenicity 2 (sST2), matrix metalloproteinase-3 (MMP-3), and galectin-3 (Gal-3) in serum plays an important role in the occurrence, development, and prognosis of cardiovascular diseases. In our study, we divided EH patients into 3 levels and groups with or without LVH, according to their condition. The levels of sST2, MMP-3, and Gal-3 in the serum were measured in different groups of patients. Our results showed that the levels of sST2, MMP-3, and Gal-3 in the serum increased progressively with the level in different EH groups. The levels of sST2, MMP-3, and Gal-3 in the serum of the LVH group were higher than those of the NLVH group, and it is positively correlated with LVH-related indexes. The risk of developing and progressing to LVH in patients with EH can be determined by the method of measuring three indicators.

The Function of ß-1,4-Glucuronosyltransferase WelK in the Sphingan WL Gum Biosynthesis Process in Marine Sphingomonas sp. WG.

The marine-derived polysaccharide WL gum produced by Sphingomonas sp. WG showed commercial utility potential in ink, food, and oil industries. A ß-1,4-glucuronosyltransferase WelK was predicted to catalyze the transfer of glucuronic acid from UDP-glucuronic acid to glucosyl-α-pyrophosphorylpolyprenol intermediate in the WL gum biosynthesis process. Its function was evaluated by bioinformatical analysis, gene knocking out, and overexpressing strategies. Compared to the wild strain, the WL gum production and broth viscosity of the mutant ∆welK were decreased by 71.5% and 99.2% when cultured for 48 h. The gene disruption led to the failure of product preparation. Homologous expression of welK in the native organism can effectively improve WL gum production. When glucose concentration was 6.7%, the WL gum production by the welK-overexpressing strain cultured for 60 h and 84 h reached 32.65 and 43.13 g/L, 134.1%, and 114% of the wild strain. The polysaccharide composition and qRT-PCR analysis showed that the glucuronic acid content was closely related to the expression level of welK. Thus, WelK was proved to play a critical role in the WL gum synthesis and will be an attractive target for metabolic engineering. Our experiment provided a genetic manipulation method for the functional characterization of genes in Sphingomonas sp. WG.

Characterization of the biosynthetic pathway of nucleotide sugar precursor UDP-glucose during sphingan WL gum production in Sphingomonas sp. WG.

To elucidate the possible biosynthetic pathway of a precursor UDP-glucose of the sphingan WL gum produced by Sphingomonas sp. WG, two enzymes phosphoglucomutase (PGM) and UDP-glucose pyrophosphorylase (UGPase) were bioinformatically analysed, expressed in Escherichia coli BL21 (DE3) and characterized. PGM was in the phosphoglucomutase/phosphomannomutase subclass and UGPase was predicted to be a UDP-glucose pyrophosphatase in a tetrameric structure. Both enzymes were expressed in soluble form, purified to near homogeneity with high activity at 1159 and 796 U/mg, exhibited folding with reasonable secondary structures, and existed as monomer and tetramer, respectively. The optimal pH and temperature of PGM were 9.0 and 50 °C, respectively, and this protein was stable at pH 8.0 and at temperatures ranging from 40 to 50 °C. The optimal pH and temperature of UGPase were 9.0 and 45 °C, respectively, and the protein was stable at pH 8.0 and at temperatures ranging from 30 to 55 °C. A small-scale one-pot biosynthesis of UDP-glucose by combining PGM and UGPase using glucose-6-phosphate and UTP as substrates was also performed, and formation of UDP-glucose was observed by HPLC detection, which confirmed the biosynthetic pathway of UDP-glucose in vitro. PGM and UGPase will be ideal targets for the metabolic engineering to improve WL gum yields in industrial production.