Polo-like kinase 1 as a biomarker predicts the prognosis and immunotherapy of breast invasive carcinoma patients

Invasive breast carcinoma(BRCA)is associated with poor prognosis and high risk of mortality.Therefore,it is critical to identify novel biomarkers for the prognostic assessment of BRCA.Methods:The expression data of polo-like kinase 1(PLK1)in BRCA and the corresponding clinical information were extracted from TCGA and GEO databases.PLK1 expression was validated in diverse breast cancer cell lines by quantitative real-time polymerase chain reaction(qRT-PCR)and western blotting.Single sample gene set enrichment analysis(ssGSEA)was performed to evaluate immune infiltration in the BRCA microenvironment,and the random forest(RF)and support vector machine(SVM)algorithms were used to screen for the hub infiltrating cells and calculate the immunophenoscore(IPS).The RF algorithm and COX regression model were applied to calculate survival risk scores based on the PLK1 expression and immune cell infiltration.Finally,a prognostic nomogram was constructed with the risk score and pathological stage,and its clinical potential was evaluated by plotting calibration charts and DCA curves.The application of the nomogram was further validated in an immunotherapy cohort.Results:PLK1 expression was significantly higher in the tumor samples in TCGA-BRCA cohort.Furthermore,PLK1 expression level,age and stage were identified as independent prognostic factors of BRCA.While the IPS was unaffected by PLK1 expression,the TMB and MATH scores were higher in the PLK1-high group,and the TIDE scores were higher for the PLK1-low patients.We also identified 6 immune cell types with high infiltration,along with 11 immune cell types with low infiltration in the PLK1-high tumors.A risk score was devised using PLK1 expression and hub immune cells,which predicted the prognosis of BRCA patients.In addition,a nomogram was constructed based on the risk score and pathological staging,and showed good predictive performance.Conclusions:PLK1 expression and immune cell infiltration can predict post-immunotherapy prognosis of BRCA patients.

Insights into the adsorption/desorption of CO_(2) and CO on single-atom Fe-nitrogen-graphene catalyst under electrochemical environment

Single-atom metal-nitrogen-graphene(M-N-Gra) catalysts are promising materials for electrocatalytic CO_(2) reduction reaction(CO_(2) RR). However, theoretical explorations on such systems were greatly hindered because of the complexity in modeling solid/liquid interface and electrochemical environment. In the current work, we investigated two crucial processes in CO_(2) RR, i.e. adsorption and desorption of CO_(2) and CO at Fe-N_(4) center, with an explicit aqueous model. We used the ab initio molecular dynamics simulations associated with free energy sampling methods and electrode potential analysis to estimate the energetics under electrochemical environment, and found significant difference in aqueous solution compared with the same process in vacuum. The effect of applied electrode potential on the adsorption structures,charge transfer and free energies of both CO_(2) and CO on Fe-N-Gra was thoroughly discussed. These findings bring insights in fundamental understandings of the CO_(2) RR process under realistic conditions, and facilitate future design of efficient M-N-Gra-based CO_2 RR catalysts.

Association of elevated hs-CRP and multiple infarctions with outcomes of minor stroke or TIA: subgroup analysis of CHANCE randomised clinical trial

Background and purpose The relationship of high-sensitive C-reactive protein(hs-CRP)levels and infarction numbers with the prognosis of stroke is uncertain.This study evaluated the association of different hs-CRP levels and infarction numbers with the prognosis of acute minor ischaemic stroke or transient ischaemic attack(TIA).Methods A subset of 807 patients with both hs-CRP measurement and baseline MRI was included from the Clopidogrel in High-risk Patients with Acute Non-disabling Cerebrovascular Events trial.The primary efficacy outcome was the occurrence of an ischaemic stroke at the 1-year follow-up.Infarction numbers were classified as multiple acute infarctions(MAIs),single acute infarction and no acute infarction(NAI).The association between different hs-CRP levels with different infarction numbers and the risk of any outcome was analysed using multivariable Cox regression models.Results Among the 807 patients,84(10.4%)patients had a recurrent ischaemic stroke within 1 year.After adjustment for conventional confounding factors,patients with both elevated hs-CRP levels and MAIs were associated with approximately 4.7-fold of risk of ischaemic stroke within 1 year(16.7% vs 3.5%,HR 4.68,95% CI 1.54 to 14.23,p=0.007),compared with those with non-elevated hs-CRP levels and NAI.Similar results were observed for the composite events.Conclusions Combined elevated hs-CRP levels and MAIs may increase 1-year stroke risk stratification efficiency in patients with minor ischaemic stroke or TIA compared with using those markers alone,which indicated that the combination of inflammatory and imaging markers might improve the effectiveness of risk stratification concerning minor ischaemic stroke or TIA.

LDL-C levels,lipid-lowering treatment and recurrent stroke in minor ischaemic stroke or TIA

Background and purpose Dyslipidaemia is a major risk factor for ischaemic stroke and transient ischaemic attack(TIA).This study aimed to investigate the association between baseline low-density lipoprotein cholesterol(LDL-C)level,lipid-lowering treatment and short-term risk of new stroke in patients with a minor ischaemic stroke or TIA.Methods We derived data from the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events trial.Patients with a minor stroke or TIA were categorised by LDL-C level at baseline(<2.6 or≥2.6 mmol/L(100 mg/dL))and with or without lipid-lowering treatment after symptom onset.The primary outcome was a new ischaemic stroke at 3 months.The association of baseline LDL-C level,lowering treatment and outcomes were assessed.Results Among 3027 patients,2154(71.2%)patients had an initial LDL-C≥2.6 mmol/L,of which 1267(41.9%)received lipid-lowering treatment.Elevated LDL-C level was associated with a higher risk of new ischaemic stroke at 3 months in patients without lipid-lowering treatment(adj.HR=1.35,95%CI:1.19 to 1.53),but not in those with lipid-lowering treatment(adj.HR=0.99,95%CI:0.82 to 1.19)(p for interaction=0.007).Patients with LDL-C≥2.6 mmol/L had a numerically higher risk of ischaemic stroke(11.8%vs 8.0%,adj.HR=1.37,95%CI:0.96 to 1.96)in those without lipid-lowering treatment.For patients with LDL-C≥2.6 mmol/L,lipid-lowering treatment was associated with reduced risk of ischaemic stroke at 3 months(7.9%vs 11.8%;adj.HR=0.54,95%CI:0.39 to 0.75).Conclusions Elevated untreated baseline LDL-C level was associated with an increased short-term risk of ischaemic stroke among patients presenting with minor ischaemic stroke or TIA.There was potential benefit of lipid-lowering treatment in minor stroke or TIA patients with LDL-C≥2.6 mmol/L.Trial registration number NCT00979589.

Residual Recurrence Risk of Ischemic Cerebrovascular Events:Elements and Implications

There has been a substantial reduction in the rate of recurrent stroke through the identification and management of risk factors including lifestyle management and achieving targets for antithrombotic medication,low-density lipoprotein cholesterol(LDL-C),blood pressure,blood sugar level,atrial fibrillation prevention,and carotid revascularization in accordance with current guideline-recommended standards of care.

Blood Biomarkers in Minor Stroke and Transient Ischemic Attack

Minor stroke and transient ischemic attack（TIA）are common disorders with a high rate of subsequent disabling stroke, so the early recognition and management of minor stroke and TIA is of great importance. At the moment, the diagnosis of these disorders is based on neurologic deficits in a stroke-clinician＇s examination of the patient, supplemented by the results of acute brain imaging.However, high variability in TIA diagnosis has been reported between physicians, even trained vascular neurologists, and image-based diagnostic confirmation is not always readily available. Some patients still have ischemic events despite sustained standard secondary preventive therapy. Blood biomarkers are promising to aid in the diagnosis, risk stratification, and individual treatment of minor stroke and TIA. Some studies are being conducted in this field. This mini-review aims to highlight potential biomarkers for diagnosis and those helpful in predicting the risk of future stroke and the selection of treatment.

Phosphorylation of Microtubule-associated Protein SB401 from Solanum berthaultii Regulates Its Effect on Microtubules

We reported previously that the protein SB401 from Solanum berthaultii binds to and bundles both microtubules and F-actin. In the current study, we investigated the regulation of SB401 activity by its phosphorylation. Our experimental results showed that the phosphorylation of SB401 by casein kinase II （CKII） downregulates the activities of SB401, namely the bundling of microtubules and enhancement of the polymerization of tubulin. However, phosphorylation of SB401 had no observable effect on its bundling of F-actin. Further investigation using extract of potato pollen indicated that a CKIl-like kinase may exist in potato pollen. Antibodies against CKII alpha recognized specifically a major band from the pollen extract and the pollen extract was able to phosphorylate the SB401 protein in vitro. The CKIl-like kinase showed a similar ability to downregulate the bundling of microtubules. Our experiments demonstrated that phosphorylation plays an important role in the regulation of SB401 activity. We propose that this phosphorylation may regulate the effects of SB401 on microtubules and the actin cytoskeleton.