The characteristics and comparison between young and old patients with spontaneous isolated celiac artery dissection: Analysis based on 60 reports.

BACKGROUND AND AIMS: Though increasing studies reported the management of spontaneous isolated celiac artery dissection (ICAD), the characteristics and etiology of ICAD in different age-stage patients have not been well-studied. Our study was designed to describe and further to compare the clinical features of spontaneous ICAD between young and old patients. METHODS: We searched PubMed, Embase, and Web of Science up to March 1, 2023 for spontaneous ICAD case reports. Two reviewers screened the titles and abstracts of searched records for qualified reports according to the including and excluding criteria and extracted the data independently. Statistical analysis was performed using SPSS software (version 19.0; IBM Corp, Armonk, NY) and Stata 12.0 (Stata Corp., College Station, TX). Descriptive results were presented as the mean ±â€…standard deviation or percent. The comparison results between young and old patients were displayed as risk ratio (RR) or standardized mean difference (SMD) with its 95% confidence intervals (CI). RESULTS: We totally identified 60 reports in the present analysis. The mean age of patients was 52.4 years, with the majority of patients being male (84.4%). The majority of patients were symptomatic and commonest presentation was abdominal pain (76.7%). Most patients (63.2%) had comorbidities or history and hypertension and smoking were the top 2 conditions with proportion of 63.3% and 40.5% respectively. When comparing young to old patients with ICAD, no significant difference was found in demographic and clinical features including sex, comorbidities/history, and symptoms. However, we found that young patients with ICAD experienced significantly longer dissection length (SMD 1.01, 95% CI 0.16-1.86; P = .015) and distance from ostium (SMD 0.96, 95% CI 0.07-1.85; P = .013), but no significant difference was observed in true lumen compression (SMD -0.39, 95% CI -1.22-0.44; P = .364). In addition, our results showed that ICAD in young patients extending more to distal arteries, including common hepatic artery/hepatic artery (RR 2.04, 95% CI 1.13-3.68; P = .01), splenic artery (RR 2.36, 95% CI 1.24-4.49; P = .017) and left gastric artery (RR 25.42; 95% CI 1.55-417.74; P = .04). CONCLUSIONS: Though spontaneous ICAD had multitudinous clinic-pathologic features, it was apt to middle-aged males and symptomatic and abdominal pain was always the commonest presentation. Hypertension and smoking were the top 2 conditions of ICAD patients. There was significant difference between young and old patients in radiographic characteristics of ICAD which may lead to different treatment and outcomes.

Preparation of Small-Pore Ultrafiltration Membranes with High Surface Porosity by In Situ CO2 Nanobubble-Assisted NIPS.

The fabrication of ultrafiltration (UF) membranes with a small pore size (<20 nm) and high surface porosity is still a great challenge. In this work, a nanobubble-assisted nonsolvent-induced phase separation (BNIPS) technique was developed to prepare high-performance UF membranes by adding a tiny amount of CaCO3 nanoparticles into the casting solution. The phase inversion occurred in a dilute-acid coagulation bath to simultaneously generate CO2 nanobubbles, which regulated the membrane structure. The effects of the nano-CaCO3 content in the casting solution on the structure and performance of poly(ethersulfone)/sulfonated polysulfone (PES/SPSf) UF membranes were studied. The UF membrane prepared from a casting solution with 0.3% nano-CaCO3 achieved a surface porosity of 12%, a pore diameter of 10.2 nm, and a skin-layer thickness of 80.3 nm. The superior structure of the UF membrane was mainly attributed to the in situ generation of CO2 nanobubbles because the CO2 nanobubbles were amphiphobic to water and solvents to delay the phase inversion time and acted as nanosize porogens. The produced membrane showed an unprecedented separation performance, achieving a pure water permeance of up to 1128 L·m-2·h-1·bar-1, 2.5 fold that of the control membrane. Similarly, a high bovine serum albumin rejection of above 99.0% was obtained. The overall permeability and selectivity were better than those of commercial and other previously reported UF membranes. This work provides insight toward a simple and cost-effective technique to address the trade-off between pure water permeance and solute rejection of UF membranes.

Efficient yeast surface-display of novel complex synthetic cellulosomes.

BACKGROUND: The self-assembly of cellulosomes on the surface of yeast is a promising strategy for consolidated bioprocessing to convert cellulose into ethanol in one step. RESULTS: In this study, we developed a novel synthetic cellulosome that anchors to the endogenous yeast cell wall protein a-agglutinin through disulfide bonds. A synthetic scaffoldin ScafAGA3 was constructed using the repeated N-terminus of Aga1p and displayed on the yeast cell surface. Secreted cellulases were then fused with Aga2p to assemble the cellulosome. The display efficiency of the synthetic scaffoldin and the assembly efficiency of each enzyme were much higher than those of the most frequently constructed cellulosome using scaffoldin ScafCipA3 from Clostridium thermocellum. A complex cellulosome with two scaffoldins was also constructed using interactions between the displayed anchoring scaffoldin ScafAGA3 and scaffoldin I ScafCipA3 through disulfide bonds, and the assembly of secreted cellulases to ScafCipA3. The newly designed cellulosomes enabled yeast to directly ferment cellulose into ethanol. CONCLUSIONS: This is the first report on the development of complex multiple-component assembly system through disulfide bonds. This strategy could facilitate the construction of yeast cell factories to express synergistic enzymes for use in biotechnology.

Engineering vesicle trafficking improves the extracellular activity and surface display efficiency of cellulases in Saccharomyces cerevisiae.

BACKGROUND: Cellulase expression via extracellular secretion or surface display in Saccharomyces cerevisiae is one of the most frequently used strategies for a consolidated bioprocess (CBP) of cellulosic ethanol production. However, the inefficiency of the yeast secretory pathway often results in low production of heterologous proteins, which largely limits cellulase secretion or display. RESULTS: In this study, the components of the vesicle trafficking from the endoplasmic reticulum (ER) to the Golgi and from the Golgi to the plasma membrane, involved in vesicle budding, tethering and fusion, were over-expressed in Clostridium thermocellum endoglucanase (CelA)- and Sacchromycopsis fibuligera ß-glucosidase (BGL1)-secreting or -displaying strains. Engineering the targeted components in the ER to Golgi vesicle trafficking, including Sec12p, Sec13p, Erv25p and Bos1p, enhanced the extracellular activity of CelA. However, only Sec13p over-expression increased BGL1 secretion. By contrast, over-expression of the components in the Golgi to plasma membrane vesicle trafficking, including Sso1p, Snc2p, Sec1p, Exo70p, Ypt32p and Sec4p, showed better performance in increasing BGL1 secretion compared to CelA secretion, and the over-expression of these components all increased BGL1 extracellular activity. These results revealed that various cellulases showed different limitations in protein transport, and engineering vesicle trafficking has protein-specific effects. Importantly, we found that engineering the above vesicle trafficking components, particularly from the ER to the Golgi, also improved the display efficiency of CelA and BGL1 when a-agglutinin was used as surface display system. Further analyses illustrated that the display efficiency of a-agglutinin was increased by engineering vesicle trafficking, and the trend was consistent with displayed CelA and BGL1. These results indicated that fusion with a-agglutinin may affect the proteins' properties and alter the rate-limiting step in the vesicle trafficking. CONCLUSIONS: We have demonstrated, for the first time, engineering vesicle trafficking from the ER to the Golgi and from the Golgi to the plasma membrane can enhance the protein display efficiency. We also found that different heterologous proteins had specific limitations in vesicle trafficking pathway and that engineering the vesicle trafficking resulted in a protein-specific effect. These results provide a new strategy to improve the extracellular secretion and surface display of cellulases in S. cerevisiae.

N-hypermannose glycosylation disruption enhances recombinant protein production by regulating secretory pathway and cell wall integrity in Saccharomyces cerevisiae.

Saccharomyces cerevisiae is a robust host for heterologous protein expression. The efficient expression of cellulases in S. cerevisiae is important for the consolidated bioprocess that directly converts lignocellulose into valuable products. However, heterologous proteins are often N-hyperglycosylated in S. cerevisiae, which may affect protein activity. In this study, the expression of three heterologous proteins, ß-glucosidase, endoglucanase and cellobiohydrolase, was found to be N-hyperglycosylated in S. cerevisiae. To block the formation of hypermannose glycan, these proteins were expressed in strains with deletions in key Golgi mannosyltransferases (Och1p, Mnn9p and Mnn1p), respectively. Their extracellular activities improved markedly in the OCH1 and MNN9 deletion strains. Interestingly, truncation of the N-hypermannose glycan did not increase the specific activity of these proteins, but improved the secretion yield. Further analysis showed OCH1 and MNN9 deletion up-regulated genes in the secretory pathway, such as protein folding and vesicular trafficking, but did not induce the unfolded protein response. The cell wall integrity was also affected by OCH1 and MNN9 deletion, which contributed to the release of secretory protein extracellularly. This study demonstrated that mannosyltransferases disruption improved protein secretion through up-regulating secretory pathway and affecting cell wall integrity and provided new insights into glycosylation engineering for protein secretion.

Engineering protein folding and translocation improves heterologous protein secretion in Saccharomyces cerevisiae.

Saccharomyces cerevisiae is widely used as a producer of heterologous proteins of medical and industrial interest. Numerous efforts have been made to overcome bottlenecks in protein expression and secretion. However, the effect of engineering protein translocation to heterologous protein secretion has not been studied extensively in S. cerevisiae. In this work, we confirmed that heterologous protein expression in S. cerevisiae induced the unfolded protein response (UPR). To enhance protein folding capacity, the endoplasmic reticulum (ER) chaperone protein BiP and the disulfide isomerase Pdi1p were each over-expressed, and the secretion of three heterologous proteins, ß-glucosidase, endoglucanase, and α-amylase, was improved. The impact of engineering key translocation components was also studied. The over-expression of co-translational translocation components Srp14p and Srp54p enhanced the secretion of three heterologous proteins (ß-glucosidase, endoglucanase, and α-amylase), but over-expressing the cytosolic chaperone Ssa1p (involved in post-translational translocation) only enhanced the secretion of ß-glucosidase. By engineering both co-translational translocation and protein folding, we obtained strains with ß-glucosidase, endoglucanase, and α-amylase activities increased by 72%, 60%, and 103% compared to the controls. Our results show that protein translocation may be a limiting factor for heterologous protein production.