Background Chronic inflammatory disorders in atrial fibrillation (AF) contribute to the onset of ischemic stroke. Systemic immune inflammation index (SIII) and system inflammation response index ...(SIRI) are the two novel and convenient measurements that are positively associated with body inflammation. However, little is known regarding the association between SIII/SIRI with the presence of AF among the patients with ischemic stroke. Methods A total of 526 ischemic stroke patients (173 with AF and 353 without AF) were consecutively enrolled in our study from January 2017 to June 2019. SIII and SIRI were measured in both groups. Logistic regression analysis was used to analyse the potential association between SIII/SIRI and the presence of AF. Finally, the correlation between hospitalization expenses, changes in the National Institutes of Health Stroke Scale (NIHSS) scores and SIII/SIRI values were measured. Results In patients with ischemic stroke, SIII and SIRI values were significantly higher in AF patients than in non-AF patients (all p < 0.001). Moreover, with increasing quartiles of SIII and SIRI in all patients, the proportion of patients with AF was higher than that of non-AF patients gradually. Logistic regression analyses demonstrated that log-transformed SIII and log-transformed SIRI were independently associated with the presence of AF in patients with ischemic stroke (log-transformed SIII: odds ratio OR: 1.047, 95% confidence interval CI = 0.322-1.105, p = 0.047; log-transformed SIRI: OR: 6.197, 95% CI = 2.196-17.484, p = 0.001). Finally, a positive correlation between hospitalization expenses, changes in the NIHSS scores and SIII/SIRI were found, which were more significant in patients with AF (all p < 0.05). Conclusions Our study suggests SIII and SIRI are convenient and effective measurements for predicting the presence of AF in patients with ischemic stroke. Moreover, they were correlated with increased financial burden and poor short-term prognosis in AF patients presenting with ischemic stroke. Keywords: Atrial fibrillation, Systemic immune inflammation index, Systemic inflammation response index, Ischemic stroke
Harnessing mitochondria is considered as a promising method for biosynthesis of terpenes due to the adequate supply of acetyl-CoA and redox equivalents in mitochondria. However, mitochondrial ...engineering often causes serious metabolic burden indicated by poor cell growth. Here, we systematically analyzed the metabolic burden caused by the compartmentalization of the MVA pathway in yeast mitochondria for squalene synthesis. The phosphorylated intermediates of the MVA pathway, especially mevalonate-5-P and mevalonate-5-PP, conferred serious toxicity within mitochondria, which significantly compromised its possible advantages for squalene synthesis and was difficult to be significantly improved by routine pathway optimization. These phosphorylated intermediates were converted into ATP analogues, which strongly inhibited ATP-related cell function, such as mitochondrial oxidative respiration. Fortunately, the introduction of a partial MVA pathway from acetyl-CoA to mevalonate in mitochondria as well as the augmentation of the synthesis of mevalonate in cytosol could significantly promote the growth of yeasts. Accordingly, a combinatorial strategy of cytoplasmic and mitochondrial engineering was proposed to alleviate the metabolic burden caused by the compartmentalized MVA pathway in mitochondria and improve cell growth. The strategy also displayed the superimposed effect of cytoplasmic engineering and mitochondrial engineering on squalene production. Through a two-stage fermentation process, the squalene titer reached 21.1 g/L with a specific squalene titer of 437.1 mg/g dcw, which was the highest at present. This provides new insight into the production of squalene and other terpenes in yeasts based on the advantages of mitochondrial engineering.
•Compartmentalizing the MVA pathway in yeast mitochondria can cause serious metabolic burden.•The phosphorylated metabolites of the MVA pathway are toxic within mitochondria.•Enhanced synthesis of mevalonate in cytosol can conquer the burden of mitochondrial engineering.•Cytoplasmic engineering is needed to take the full advantage of mitochondrial engineering.
AbstractUnlike carbon-fiber-reinforced polymer (CFRP) bars and the maturely developed glass FRP (GFRP) bars, the long-term performance of the newly developed basalt-fiber reinforced polymer (BFRP) ...bars under severe environmental conditions remains unclear. This paper evaluates the residual tensile properties of unstressed and stressed BFRP bars exposed to four types of simulated harsh environments: alkaline solution, salt solution, acid solution, and de-ionized water at 25, 40, and 55°C. Microstructural analysis using scanning electronic microscopy (SEM) was also conducted to reveal the inherent degradation mechanism of BFRP bars in alkaline environment. The residual tensile strength of unstressed BFRP bars exposed to alkaline solution was used for long-term performance prediction based on Arrhenius theory. The results showed that the effect on the durability of BFRP bars exposed to acid, salt, and deionized water was less than that for bars exposed to alkaline solution. The effects of sustained stress on the degradation of BFRP bars were not obvious when the stress level was less than 20% of the ultimate strength, but if the stress exceeded this level, the degradation processes were accelerated. The predicted exposure time required for a reduction in strength of 50% at a mean annual temperature of 5.7°C in alkaline solution, which represents an area with a northern latitude of 50°, was estimated at approximately 16.1 years for the 6-mm BFRP bar.
STING (also known as MITA) is critical for host defence against viruses and the activity of STING is regulated by ubiquitination. However, the deubiquitination of STING is not fully understood. Here, ...we show that ubiquitin-specific protease 13 (USP13) is a STING-interacting protein that catalyses deubiquitination of STING. Knockdown or knockout of USP13 potentiates activation of IRF3 and NF-κB and expression of downstream genes after HSV-1 infection or transfection of DNA ligands. USP13 deficiency results in impaired replication of HSV-1. Consistently, USP13 deficient mice are more resistant than wild-type littermates to lethal HSV-1 infection. Mechanistically, USP13 deconjugates polyubiquitin chains from STING and prevents the recruitment of TBK1 to the signalling complex, thereby negatively regulating cellular antiviral responses. Our study thus uncovers a function of USP13 in innate antiviral immunity and provides insight into the regulation of innate immunity.
An efficient and practical method for the one-step synthesis of benzothiazole-2-thiols, benzoxazole-2-thiols and benzimidazoline-2-thiones by cyclization of 2-aminothiophenols, 2-aminophenols, and ...1,2-phenylenediamines with tetramethylthiuram disulfide (TMTD) in water was described. The features of this method include metal/ligand-free, excellent yield, short reaction time and broad substrate scope. The method provides a facile and convenient preparation of some potentially biologically active compounds.
An efficient tandem process for the preparation of 2-arylthiobenzothiazoles has been developed. By condensation of 2-aminobenzenethiol with tetramethylthiuram disulfide (TMTD), ...2-mercaptobenzothiazoles was in situ generated, which susequently underwent coupling with iodobenzenes to give the desired 2-arylthiobenzothiazoles fluently in a one-pot manner. This method can also be used for the synthesis of 2-arylthiobenzoxazoles. Inexpensive metal catalyst and ligand, mild reaction temperature, and water as solvent make this protocol practically valuable and useful in organic synthesis.
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and shows a propensity to metastasize and infiltrate adjacent and more distant tissues. HCC is associated with multiple risk ...factors, including hepatitis B virus (HBV) infection, which is especially prevalent in China. Here, we used exome sequencing to identify somatic mutations in ten HBV-positive individuals with HCC with portal vein tumor thromboses (PVTTs), intrahepatic metastases. Both C:G>A:T and T:A>A:T transversions were frequently found among the 331 non-silent mutations. Notably, ARID1A, which encodes a component of the SWI/SNF chromatin remodeling complex, was mutated in 14 of 110 (13%) HBV-associated HCC specimens. We used RNA interference to assess the roles of 91 of the confirmed mutated genes in cellular survival. The results suggest that seven of these genes, including VCAM1 and CDK14, may confer growth and infiltration capacity to HCC cells. This study provides a view of the landscape of somatic mutations that may be implicated in advanced HCC.
An efficient and convenient procedure for the S‐arylation of tetraalkylthiuram disulfides by using diaryliodonium salts was explored. In the presence of CuI/KOtBu, two kinds of S‐aryl ...dithiocarbamates could be obtained in good to excellent yields at one time with no clear selectivity. This method has the advantages of efficiency, good atom economy, and broad substrate scope. This protocol allows the facile and convenient preparation of some potentially biologically active compounds.
An efficient and convenient procedure for the S‐arylation of tetraalkylthiuram disulfides by using diaryliodonium salts is explored. In the presence of CuI/KOtBu, two kinds of S‐aryl dithiocarbamates are obtained in good to excellent yields at one time with no clear selectivity. This method has the advantages of efficiency, good atom economy, and broad substrate scope.
Photonic crystal (PC) materials have huge potentials as sensors for noninvasive and real-time monitoring glucose in tears. We developed a glucose-sensitive PC material based on monolayered colloidal ...crystals (MCCs). Polystyrene nanoparticles were first self-assembled into a highly ordered MCC, and this two-dimensional (2D) template was then coated by a 4-boronobenzaldehyde-functionalized poly(vinyl alcohol) hydrogel. Such a sensor efficiently diffracts visible light, whose structural color could change from red through yellow to green, as the glucose concentration altered from 0 to 20 mM, covering both tears’ and bloods’ physiological ranges. The sensor also represents a rapid response within 180 s at each titration of glucose, combining the characteristics of high accuracy and sensitivity in detecting the glucose concentration in tears, and this intelligent sensing material presents certain possibility for the frontier point-of-care glucose monitoring.
The reconstruction of irradiated bone defects after settlement of skeletal tumors remains a significant challenge in clinical applications. In this study, we explored radiation‐induced skeletal stem ...cell (SSC) stemness impairments and rescuing effects of ferulic acid (FA) on SSCs in vitro and in vivo. The immunophenotype, cell renewal, cell proliferation, and differentiation of SSCs in vitro after irradiation were investigated. Mechanistically, the changes in tissue regeneration‐associated gene expression and MAPK pathway activation in irradiated SSCs were evaluated. The regenerative capacity of SSCs in the presence of FA in an irradiated bone defect mouse model was also investigated. We found that irradiation reduced CD140a‐ and CD105‐positive cells in skeletal tissues and mouse‐derived SSCs. Additionally, irradiation suppressed cell proliferation, colony formation, and osteogenic differentiation of SSCs. The RNA‐Seq results showed that tissue regeneration‐associated gene expression decreased, and the Western blotting results demonstrated the suppression of phosphorylated p38/MAPK and ERK/MAPK in irradiated SSCs. Notably, FA significantly rescued the radiation‐induced impairment of SSCs by activating the p38/MAPK and ERK/MAPK pathways. Moreover, the results of imaging and pathological analyses demonstrated that FA enhanced the bone repair effects of SSCs in an irradiated bone defect mouse model substantially. Importantly, inhibition of the p38/MAPK and ERK/MAPK pathways in SSCs by specific chemical inhibitors partially abolished the promotive effect of FA on SSC‐mediated bone regeneration. In summary, our findings reveal a novel function of FA in repairing irradiated bone defects by maintaining SSC stemness and suggest that the p38/MAPK and ERK/MAPK pathways contribute to SSC‐mediated tissue regeneration postradiation.
Irradiation caused significant impairment of skeletal stem cell (SSC) stemness via inactivation of MAPK pathways. Ferulic acid (FA) rescued the irradiated SSC partially via reactivated MAPK signaling.
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