Importance of AIM2 as a serum marker for reflecting severity and predicting a poor outcome of human severe traumatic brain injury: A prospective longitudinal cohort study.

BACKGROUND: Absent in melanoma 2 (AIM2) participates in neuroinflammation. Here, the prognostic significance of serum AIM2 was explored in severe traumatic brain injury (sTBI). METHODS: A total of 135 sTBI patients and 80 healthy controls were recruited in this prospective cohort study. Serum C-reactive protein (CRP) and AIM2 levels were measured. Glasgow Coma Scale (GCS) and Rotterdam computed tomography (CT) classification were recorded as the severity indicators. Prognostic parameters were posttraumatic six-month extended Glasgow outcome scale (GOSE) scores and poor outcome (GOSE scores of 1-4). RESULTS: As opposed to controls, there were significantly elevated serum AIM2 levels after sTBI. Serum AIM2 levels were independently correlated with serum CRP levels, GCS scores, Rotterdam CT scores, GOSE scores and poor outcome. Also, serum AIM2 levels were efficiently predictive of poor outcome under the receiver operating characteristic (ROC) curve. Under the restricted cubic spline, serum AIM2 levels were linearly correlated with risk of poor outcome. Using subgroup analysis, serum AIM2 levels did not significantly interact with other indices, such as age, gender, alcohol drinking, cigarette smoking, etc. Also, combination model, in which serum AIM2, GCS scores and Rotterdam CT scores were merged, was outlined using nomogram and performed well under calibration curve, ROC curve and decision curve. CONCLUSIONS: Raised serum AIM2 levels after sTBI, in intimate correlation with systemic inflammation and trauma severity, are independently discriminative of posttraumatic six-month neurological outcome, substantializing serum AIM2 as an inflammatory prognostic biomarker of sTBI.

Sphaerotilus natans hemoglobins have an NADH oxidation activity and promote the yield of limonene in an engineered E. coli strain.

Bacterial hemoglobins play important roles inside the cell. Phylogenetically, they belong to three different families: the single domain hemoglobin, flavohemoglobin and truncated hemoglobin. Vitreoscilla hemoglobin (VHb) is the first characterized bacterial hemoglobin, and belongs to the single domain hemoglobin family. Heterologous expression of VHb promotes the growth of host cells under microaerobic conditions, and enhances the yield of products during fermentation. Although VHb has been widely applied in the biotechnology field, other bacterial hemoglobins have not demonstrated similar applications. In this study, we identified four bacterial hemoglobins from the microaerobic growing bacterium Sphaerotilus natans, including one flavohemoglobins (FHB) and three truncated hemoglobins (THB1, THB2 and THB3). Absorption spectrum studies validate the existent of the Soret peak and Q-band characteristic to heme and suggest heme groups in FHB and THB1 are hexa- or penta-coordinated, respectively. Our studies demonstrate that FHB and all three truncated hemoglobins have NADH oxidation and radical production activities, which is surprising since truncated hemoglobins do not have a reductase domain that could bind NADH. However, the M. tuberculosis HbN does not show these activities, indicating they are not universal among truncated hemoglobins. Docking studies suggest the nicotinamide ring of NADH may bind to the distal heme pocket of THB1, suggesting the direct electron transfer from NADH to heme might be possible. Our truncated hemoglobins also show peroxidase activities that in THB2 and THB3 could be inhibited by FdR, indicating possible interactions between FdR and truncate hemoglobins. Expression of FHB and THB1 in E. coli could promote cell growth. THB1 also enhances the production of limonene in an engineered E. coli strain, while VHb does not have this effect, which suggests that studies on truncated hemoglobins may lead to the discovery of new and more powerful tools that could have profound impact on biotechnology.

Targeting tau in Alzheimer's disease: from mechanisms to clinical therapy.

ABSTRACT: Alzheimer's disease is the most prevalent neurodegenerative disease affecting older adults. Primary features of Alzheimer's disease include extracellular aggregation of amyloid-ß plaques and the accumulation of neurofibrillary tangles, formed by tau protein, in the cells. While there are amyloid-ß-targeting therapies for the treatment of Alzheimer's disease, these therapies are costly and exhibit potential negative side effects. Mounting evidence suggests significant involvement of tau protein in Alzheimer's disease-related neurodegeneration. As an important microtubule-associated protein, tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth. In fact, clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-ß in the brain. Various therapeutic strategies targeting tau protein have begun to emerge, and are considered possible methods to prevent and treat Alzheimer's disease. Specifically, abnormalities in post-translational modifications of the tau protein, including aberrant phosphorylation, ubiquitination, small ubiquitin-like modifier (SUMO)ylation, acetylation, and truncation, contribute to its microtubule dissociation, misfolding, and subcellular missorting. This causes mitochondrial damage, synaptic impairments, gliosis, and neuroinflammation, eventually leading to neurodegeneration and cognitive deficits. This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer's disease and discusses tau-targeted treatment of Alzheimer's disease.

Investigating Students' Satisfaction with Online Collaborative Learning During the COVID-19 Period: An Expectation-Confirmation Model.

The recent outbreak of COVID-19 posed discontinuous disruption to traditional learning modes worldwide. In order to keep social distance, online collaborative learning has become a necessity during the pandemic. However, our understanding of students' well-being and satisfaction with online collaborative learning is limited, especially during the COVID-19 period. Leveraging expectation confirmation theory, this study focuses on the triggers and inhibitors of students' cognitive load during online collaborative learning process and their subsequent satisfaction with the learning mode during the pandemic. We used a mixed-method approach in this study. We conducted a qualitative study with interview data and a quantitative study with surveys. The results indicate several psychological and cognitive antecedents of students' cognitive load during online collaborative learning. Findings also indicate that a high level of cognitive load will decrease students' perceived usefulness of the online learning platform and expectation confirmation, thus leading to a low level of satisfaction with online collaborative learning. This study can provide theoretical and practical implications for a better understanding of online student groups' satisfaction with online collaborative learning during the COVID-19 period.

Overexpression of hsa_circ_0001445 reverses oxLDL­induced inhibition of HUVEC proliferation via SRSF1.

Atherosclerosis is a primary cause of multiple types of cardiovascular disease, including myocardial infarction. In addition, injury of human umbilical vein endothelial cells (HUVECs) can lead to the development of atherosclerosis. Circular (circ)RNAs participate in atherosclerosis. It has previously been shown that circRNA cSMARCA5 (hsa_circ_0001445) expression is downregulated in atherosclerosis. However, the effects of hsa_circ_0001445 on the proliferation of HUVECs remain unclear. In order to mimic atherosclerosis in vitro, HUVECs were treated with oxidized low­density lipoprotein (oxLDL). The expression levels of specific genes and proteins were detected in HUVECs by reverse transcription­quantitative PCR and western blot analysis, respectively. Cell proliferation was assessed by Cell Counting Kit­8 and 5­Ethynyl­2'­deoxyuridine staining. Cell apoptosis and 5,5',6,6'­Tetrachloro­1,1',3,3'­tetraethyl­imidacarbocyanine staining were examined by flow cytometry. In addition, the association between hsa_circ_0001445 and serine/arginine­rich splicing factor 1 (SRSF1) was investigated by RNA pull­down assay. hsa_circ_0001445 expression was downregulated in oxLDL­treated HUVECs. Moreover, oxLDL­induced inhibition of HUVEC proliferation was significantly reversed by overexpression of hsa_circ_0001445. oxLDL notably inhibited tube formation and mitochondrial membrane potential in HUVECs, while these effects were markedly reversed by hsa_circ_0001445 overexpression. Furthermore, overexpression of hsa_circ_0001445 reversed oxLDL­induced activation of ß­catenin by binding to SRSF1. Collectively, these data demonstrated that overexpression of hsa_circ_0001445 reversed oxLDL­induced inhibition of HUVEC proliferation via activation of the SRSF1/ß­catenin axis. These findings may provide novel targets for the treatment of atherosclerosis.

Ability of serum annexin A1 to predict 6-month poor clinical outcome following aneurysmal subarachnoid hemorrhage.

BACKGROUND: Annexin A1 might be neuroprotective and serum annexin A1 concentrations were markedly declined after severe traumatic brain injury. We determine dthe ability of serum annexin A1 to assess severity and predict prognosis after aneurysmal subarachnoid hemorrhage (aSAH). METHODS: We included 157 aSAH patients and 157 healthy subjects. Serum annexin A1 measurements were measured. A poor outcome was designated as Glasgow outcome scale score of 1-3. Multivariate logistic regression analysis was applied to identify predictors of a poor 6-month outcome. RESULTS: Serum annexin A1 concentrations were significantly lower in patients than in controls. Annexin A1 concentrations were strongly correlated with the World Federation of Neurological Surgeons scale (WFNS) score, Hunt-Hess score, Glasgow coma scale score and modified Fisher score. A total of 59 patients (37.6%) experienced a poor outcome. Serum annexin A1, WFNS score and modified Fisher score emerged as the 3 independent predictors for a poor outcome after aSAH. Under ROC curve analysis, serum annexin A1 had a fair accuracy to predict a poor outcome, AUC of serum annexin A1 concentration was equivalent to those of WFNS score and modified Fisher score and AUC of combination of the 3 factors significantly exceeded that of each one alone. CONCLUSIONS: Annexin A1 may be involved in the occurrence and progression of secondary brain injury after aSAH. Detection of serum annexin A1 may have certain ability for assessment of severity and prediction of long-term prognosis following aSAH.

Potential role of serum substance P as a favorable biomarker of functional outcome in acute spontaneous intracerebral hemorrhage.

BACKGROUND: Substance P (SP) is implicated in brain inflammation. We clarified relationship between serum SP concentrations and functional outcome of acute intracerebral hemorrhage (ICH). METHODS: We quantified admission serum SP concentrations in 106 ICH patients. The primary outcome measure was a poor outcome at 90 days (modified Rankin Scale score ≥ 3) after onset. RESULTS: Patients with a poor outcome compared with the rest had substantially higher serum SP concentrations. The area under the curve for serum SP concentrations with regard to discriminating a poor outcome was 0.795 (95% CI, 0.706 to 0.867). Serum SP concentrations >449 pg/ml predicted the risk of a poor outcome with 63.0% sensitivity and 78.9% specificity, and were independently associated with a poor outcome (odds ratio, 5.437; 95% CI, 2.156 to 13.715). There were the positive associations between serum SP concentrations, National Institutes of Health Stroke Scale score (r = 0.480), hematoma volume (r = 0.464) and serum C-reactive protein concentrations (r = 0.398). CONCLUSIONS: Higher serum SP concentrations in the acute phase of ICH were intimately associated with aggravated inflammation response, rising severity and increased risk of a poor functional outcome, suggesting that serum SP could be an inflammatory prognostic factor for ICH.

Molecularly imprinted ultrathin graphitic carbon nitride nanosheets-Based electrochemiluminescence sensing probe for sensitive detection of perfluorooctanoic acid.

Driven by the urgent demand for the determination of low level perfluorooctanoic acid (PFOA) present in environment, a novel electrochemiluminescence (ECL) sensor has been first developed for the detection of PFOA using the molecularly imprinted polypyrrole modified two-dimensional ultrathin g-C3N4 (utg-C3N4) nanosheets as a cathodic ECL emitter with S2O8(2-) as coreactant. The prepared molecularly imprinted polymer (MIP) functionalized utg-C3N4 nanosheets (MIP@utg-C3N4) exhibit a stable and significantly amplified ECL signal. It is found that the targets of PFOA could be efficiently oxidized by the electro-generated strong oxidants of SO4(-) (from the reduction of coreactant S2O8(2-)), thus leading to a low yield of the excited utg-C3N4 (g-C3N4*) and finally a decrease in ECL signal. Based on this, a highly sensitive and selective MIP@utg-C3N4-based signal-off ECL sensor is developed for sensing PFOA. Such a newly designed ECL sensor exhibits highly linear over the PFOA concentration in two ranges, from 0.02 to 40.0 ng mL(-1) and 50.0-400.0 ng mL(-1). The detection limit (S/N = 3) is estimated to be 0.01 ng mL(-1) (i.e. 0.01 ppb), comparable to the results obtained by using well-established liquid chromatography-tandem mass spectrometry (LC-MS/MS). Toward practical applications, this low-cost and sensitive assay was successfully applied to measure PFOA in real water samples, showing fine applicability for the detection of PFOA in real samples.

Neural stem cell transplantation promotes behavioral recovery in a photothrombosis stroke model.

Stem cell-based therapy provides a promising approach for treat stroke. Neural stem cells isolated from mice hippocampus possessing the capacity of differentiate into neurons and astrocytes both in vitro and vivo. Here, we investigated the capability of neural stem cell transplantation in photothrombosis stroke model. Nissl staining revealed that the cortical infarct significantly decreased by 16.32% (Vehicle: 27.93le: an mm(3), n=6, NSC: 23.37le: ai mm(3), n=6, P<0.05) in the NSC group compared with the vehicle. More over transplantation of neural stem cells significantly (P<0.01) improved neurological performance compared with vehicle. These results indicate that transplantation of neural stem cell is an effective therapy in ischemic stroke.

The study on stage financing model of IT project investment.

Stage financing is the basic operation of venture capital investment. In investment, usually venture capitalists use different strategies to obtain the maximum returns. Due to its advantages to reduce the information asymmetry and agency cost, stage financing is widely used by venture capitalists. Although considerable attentions are devoted to stage financing, very little is known about the risk aversion strategies of IT projects. This paper mainly addresses the problem of risk aversion of venture capital investment in IT projects. Based on the analysis of characteristics of venture capital investment of IT projects, this paper introduces a real option pricing model to measure the value brought by the stage financing strategy and design a risk aversion model for IT projects. Because real option pricing method regards investment activity as contingent decision, it helps to make judgment on the management flexibility of IT projects and then make a more reasonable evaluation about the IT programs. Lastly by being applied to a real case, it further illustrates the effectiveness and feasibility of the model.