A prospective cohort study on serum A20 as a prognostic biomarker of aneurysmal subarachnoid hemorrhage

BACKGROUND:A20 may be a neuroprotective factor.Herein,we aimed to investigate whether serum A20 levels were associated with disease severity,delayed cerebral ischemia(DCI),and outcome after aneurysmal subarachnoid hemorrhage(aSAH).METHODS:In this prospective cohort study containing 112 aSAH patients and 112 controls,serum A20 levels were quantified.At 90 d poststroke,Modified Rankin Scale(MRS) scores≥3 were defined as a poor outcome.All correlations and associations were assessed using multivariate analysis.RESULTS:Compared with controls,there was a significant elevation of serum A20 levels in patients(median 123.7 pg/mL vs.25.8 pg/mL;P<0.001).Serum A20 levels were independently correlated with Hunt-Hess scores(β 9.854;95% confidence interval [95% CI] 2.481-17.227,P=0.009) and modified Fisher scores(β 10.349,95% CI 1.273-19.424,P=0.026).Independent associations were found between serum A20 levels and poor outcome(odds ratio [OR] 1.015,95%CI 1.000-1.031,P=0.047) and DCI(OR 1.018,95% CI 1.001-1.035,P=0.042).Areas under the curve for predicting poor outcome and DCI were 0.771(95% CI 0.682-0.845) and 0.777(95% CI 0.688-0.850),respectively.Serum A20 levels ≥128.15 pg/mL predicted poor outcome,with a sensitivity of 73.9% and specificity of 74.2%,and A20 levels ≥160.55 pg/mL distinguished the risk of DCI with65.5% sensitivity and 89.2% specificity.Its ability to predict poor outcome and DCI was similar to those of Hunt-Hess scores and modified Fisher scores(both P>0.05).CONCLUSION:Enhanced serum A20 levels are significantly associated with stroke severity and poor clinical outcome after aSAH,implying that serum A20 may be a potential prognostic biomarker for aSAH.

The enhanced genomic 6mA metabolism contributes to the proliferation and migration of TSCC cells

In contrast to the well-established genomic 5-methylcytosine(5mC),the existence of N^(6)-methyladenine(6 mA)in eukaryotic genomes was discovered only recently.Initial studies found that it was actively regulated in cancer cells,suggesting its involvement in the process of carcinogenesis.However,the contribution of 6 mA in tongue squamous cell carcinoma(TSCC)still remains uncharacterized.In this study,a pan-cancer type analysis was first performed,which revealed enhanced 6mA metabolism in diverse cancer types.The study was then focused on the regulation of 6 mA metabolism,as well as its effects on TSCC cells.To these aspects,genome 6mA level was found greatly increased in TSCC tissues and cultured cells.By knocking down 6mA methylases N6AMT1 and METTL4,the level of genomic 6mA was decreased in TSCC cells.This led to suppressed colony formation and cell migration.By contrast,knockdown of 6mA demethylase ALKBH1 resulted in an increased 6 mA level,enhanced colony formation,and cell migration.Further study suggested that regulation of the NF-κB pathway might contribute to the enhanced migration of TSCC cells.Therefore,in the case of TSCC,we have shown that genomic 6mA modification is involved in the proliferation and migration of cancer cells.

Strengthening synergistic effects between hard carbon and soft carbon enabled by connecting precursors at molecular level towards high-performance potassium ion batteries

Synergistic effects between hard carbons and soft carbons are proven to be helpful for improving the electrochemical performance of carbonaceous anode for potassium-ion batteries(PIBs).However,the phase separation of precursors limits the synergistic effects and improvement of electrochemical performance.Here,inspired by the esterification reaction,the precursors of two sorts of carbon are connected at the molecular level,which boosts the synergistic effects in hybrid carbon,resulting in excellent electrochemical kinetics and low charge/discharge voltage.Consequently,the hybrid carbon anode exhibited a high specific capacity of 121 mAh·g^(−1)at 3.2 A·g^(−1),a high-rate capability,and stable cycling performance.After 500 cycles at 1 A·g^(−1),the average capacity fading is only 0.078%per cycle.

Exogenous nucleic acids aggregate in non-P-body cytoplasmic granules when transfected into cultured cells

To modulate gene expression in research studies or in potential clinical therapies,transfection of exogenous nucleic acids including plasmid DNA and small interference RNA(siRNA)are generally performed.However,the cellular processing and the fate of these nucleic acids remain elusive.By investigating the cellular behavior of transfected nucleic acids using confocal imaging,here we show that when siRNA was cotransfected into cultured cells with other nucleic acids,including single-stranded RNA oligonucleotides,single and double-stranded DNA oligonucleotides,as well as long double-stranded plasmid DNA,they all aggregate in the same cytoplasmic granules.Interestingly,the amount of siRNA aggregating in granules was found not to correlate with the gene silencing activity,suggesting that assembly of cytoplasmic granules triggered by siRNA transfection may be separable from the siRNA silencing event.Our results argue against the claim that the siRNAaggregating granules are the functional site of RNA interference(RNAi).Taken together,our studies suggest that,independent of their types or forms,extraneously transfected nucleic acids are processed through a common cytoplasmic pathway and trigger the formation of a new type of cytoplasmic granules“transfection granules”.

Effects of chain length and hydrophobicity/charge ratio of AMP on its antimicrobial activity

Using two series of de novo designed antimicrobial peptides,we studied the effects of peptide length and hydrophobicity/charge(H/C) ratio on the antimicrobial activities.For these peptides,a correlation was established between their antimicrobial efficacy and the leakage,aggregation,and fusion activities on artificial membrane.The results showed that peptides with an H/C ratio of 1.3,and a length of about half of the membrane thickness caused most potent membrane leakage,and negligible membrane aggregation and fusion.In addition,such peptide also exhibited the highest antimicrobial activity.Analysis of the hydrophobic and electrostatic interactions showed that the strength,the order and the position of these interactions determined the activities of the peptides on the artificial membrane and thus the antimicrobial efficacy.Further analyses on the tilt angle of the peptides on the membrane surface indicated that the peptides distorted the membrane in a dynamic mode,instead of being fixed in the membrane at a constant angle.

Serum Copeptin and In-Hospital Major Adverse Events after Head Trauma: A Multicenter Study

Background: Copeptin is a biomarker for brain injury. However,it is unclear whether it is discriminative regarding in-hospital major adverse events (IMAEs),including acute lung injury,acute traumatic coagulopathy,progressive hemorrhagic injury and post-traumatic cerebral infarction,in patients with traumatic brain injury (TBI). This study was aimed at investigating the relationship between the serum copeptin level and occurrences of IMAEs. Methods: In this multicenter observational study,we recruited 173 severe TBI patients and 173 healthy controls. Serum levels of copeptin,interleukin-6,tumor necrosis factor-alpha,C-reactive protein,myelin basic protein,glial fibrillary astrocyte protein,S100B,neuron-specific enolase,phosphorylated axonal neurofilament subunit H,tau protein and ubiquitin carboxyl-terminal hydrolase L1 were quantified using available enzyme-linked immunosorbent assays. Areas under the receiver operating characteristic curves (AUCs) were estimated to determine and compare their discriminatory ability for IMAEs. Results: Patients had dramatically elevated levels of the afore-mentioned biomarkers,as compared with controls. In the discrimination of IMAEs,serum copeptin had a significantly higher AUC than serum interleukin-6,tumor necrosis factor-alpha and C-reactive protein and its AUC was similar to that of the Glasgow coma scale (GCS) score and the other remaining biomarkers mentioned above. Except copeptin,no other biomarkers could significantly improve the AUC of the GCS score. Conclusion: Serum copeptin levels combined with the GCS score might aid in discriminating IMAEs following TBI.