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Abstract Ulinastatin, a broad-spectrum inflammatory inhibitor widely employed in the management of severe pancreatitis and sepsis, has not been extensively investigated for its therapeutic potential in bacterial meningitis. This study aims to assess the neuroprotective effects of ulinastatin on bacterial meningitis and elucidate its underlying mechanism. The rat model of bacterial meningitis was established by intracerebral injection of Escherichia coli. 3-week-old SD rats were randomly divided into 5 groups with 8 rats in each group, including control group, E.coli group, E.coli + UTI group (ulinastatin 50000IU/kg), E.coli + UTI + PMA group (ulinastatin 50000IU/kg + PMA 200 ug/kg), and E.coli + PMA group(PMA 200 ug/kg). Behavioral changes were assessed by Loeffler neurobehavioral score. Histomorphologic changes and apoptosis were assessed by hematoxylin and eosin staining, Nissl staining and TUNEL staining. Immunohistochemistry and immunofluorescence and western blotting were used to detect the expression levels of zonula occludens-1 (ZO-1) and phosphorylation protein kinase C (PKCα).It was found that ulinastatin treatment in Escherichia coli meningitis rats improved neurological function, alleviated meningeal inflammatory infiltration, reduced neuronal death, promoted the integrity of the blood–brain barrier structure. Moreover, phorbol myristate acetate (PMA, a protein kinase C activator), blocked the effective action of ulinastatin. These findings suggest that ulinastatin had neuroprotective effects on bacterial meningitis by inhibiting PKCα phosphorylation and reducing ZO-1 degradation, demonstrating that ulinastatin may be a promising strategy in the treatment of bacterial meningitis.

Abstract Background APRI and FIB-4 scores are used to exclude clinically significant fibrosis (defined as stage ≥ F2) in patients with chronic viral hepatitis. However, the cut-offs for these scores (generated by Youden indices) vary between different patient cohorts. This study aimed to evaluate whether serum dithiothreitol-oxidizing capacity (DOC), i.e., a surrogate test of quiescin sulfhydryl oxidase-1, which is a matrix remodeling enzyme, could be used to non-invasively identify significant fibrosis in patients with various chronic liver diseases (CLDs). Methods Diagnostic performance of DOC was compared with APRI and FIB-4 for identifying significant fibrosis. ROC curve analyses were undertaken in: a) two chronic hepatitis B (CHB) cohorts, independently established from hospitals in Wenzhou (n = 208) and Hefei (n = 120); b) a MASLD cohort from Wenzhou hospital (n = 122); and c) a cohort with multiple CLD etiologies (except CHB and MASLD; n = 102), which was identified from patients in both hospitals. Cut-offs were calculated using the Youden index. All CLD patients (n = 552) were then stratified by age for ROC curve analyses and cut-off calculations. Results Stratified by CLD etiology or age, ROC curve analyses consistently showed that the DOC test was superior to APRI and FIB-4 for discriminating between clinically significant fibrosis and no fibrosis, when APRI and FIB-4 showed poor/modest diagnostic performance (P 0.05 in 11 cohort comparisons). DOC had a significant advantage over APRI or FIB-4 scores for establishing a uniform cut-off independently of age and CLD etiology (coefficients of variation of DOC, APRI and FIB-4 cut-offs were 1.7%, 22.9% and 47.6% in cohorts stratified by CLD etiology, 2.0%, 26.7% and 29.5% in cohorts stratified by age, respectively). The uniform cut-off was 2.13, yielded from all patients examined. Surprisingly, the uniform cut-off was the same as the DOC upper limit of normal with a specificity of 99%, estimated from 275 healthy control individuals. Hence, the uniform cut-off should possess a high negative predictive value for excluding significant fibrosis in primary care settings. A high DOC cut-off with 97.5% specificity could be used for detecting significant fibrosis (≥ F2) with an acceptable positive predictive value (87.1%). Conclusions This proof-of-concept study suggests that the DOC test may efficiently rule out and rule in significant liver fibrosis, thereby reducing the numbers of unnecessary liver biopsies. Moreover, the DOC test may be helpful for clinicians to exclude significant liver fibrosis in the general population.

In this paper, N-vinylpyrrolidone was copolymerized with acrylic acid and itaconic acid by free radical polymerization, and a series of polyacrylic acid-co-itaconic acid-co-N-vinylpyrrolidone (PAIN) dispersants with different pyrrolidone ligand contents were synthesized and characterized. Then, the cobalt blue nano-pigment slurry (20 wt%) was prepared through a water-based grinding method, and the optimum grinding technology was explored and determined as follows: PAIN2 as a dispersant, a dispersant dosage of 10 wt%, and a grinding time of 480 min. According to this optimum grinding technology, the prepared pigment slurry had a significantly decreased agglomeration, the D90 of which was 82 nm, and separately increased to 130 nm and 150 nm after heat storage for 3 and 7 days, exhibiting excellent heat storage stability. Additionally, its TSI value was also the lowest (1.9%), indicating good dispersion stability. The QCM and adorption capacity measuring results showed PAIN2 had a larger adsorption capacity, and the formed adsorption layer had a higher rigidity and was not easy to fall off. This was caused by both the interaction of carboxyl groups and the pyrrolidone ligand (strong coordination interaction) in PAIN2 with cobalt blue. The XPS and FT–IR measurements further proved the above-mentioned adsorption mechanism.

Improving the thermal storage stability of nanosuspension concentrate (SC) prepared from low-melting-point pesticide is a recognized problem. In this work, using pyraclostrobin as the raw material, 25 wt% of pyraclostrobin nano-SC was prepared through a water-based grinding method, and the optimal grinding conditions were obtained as follows: a grinding time of 23 h, D-3911 as dispersant and a dispersant dosage of 12 wt%. The pyraclostrobin nano-SC D90 size prepared based on this best formula was 216 nm. Adding glycerin could improve the stability of nano-SC at room temperature, but its thermal storage stability was still poor. For this problem, sodium lignosulfonate and cetyltrimethylammonium bromide (NaLS/CTAB) colloidal spheres were prepared through electrostatic and hydrophobic self-assembly and characterized. The delamination and precipitation of nano-SC can be significantly improved by adding an appropriate amount of colloidal spheres, and the nano-SC D90 size decreased from 2726 to 1023 nm after 7 days of thermal storage. Farmland experiments indicated the control efficiency of pyraclostrobin nano-SC against flowering cabbage downy mildew disease was about 30% higher than that of SC. Especially after adding the wetting agent, the effect of nano-SC could be comparable to that of commercial Kairun (currently the best pyraclostrobin formulation in the world).

Background: Endometrial infertility accounts for a significant proportion of infertility cases, and single-cell transcriptome data have revealed that hub genes may play an important role during pregnancy. Methods: Based on the endometrial single-cell sequencing data from National Center for Biotechnology Information (NCBI) database, we performed clustering, staging, and functional analyses to screen and validate key genes affecting endometrial infertility. Results: Through bioinformatics analysis, we found that the proportion of ciliated cells peaked from the early to mid secretory phase, ciliary motility decreased in the mid secretory phase, while the hub gene that connexin 43 (GJA1) and secreted phosphoprotein 1 (SPP1) expressed in the endometrium may determine successful pregnancy. In immunohistochemistry validation, GJA1 and SPP1 were significantly highly expressed in the endometrium of a normal pregnancy, compared to recurrent miscarriage. Similarly, GJA1 and SPP1 were expressed higher in the fetal villus of a normal pregnancy as compared to recurrent miscarriage, while no difference was found in the decidua. CellPhoneDB and protein–protein interactions (PPIs) indicated an interaction among notch receptor 1 (NOTCH1), GJA1 and SPP1. Conclusions: GJA1 and SPP1 exhibit higher expression levels in the endometrium and fetal villus of a normal pregnancy as compared to recurrent miscarriage, suggesting that GJA1 and SPP1 may play a pivotal role in endometrial infertility.