Background and purpose To investigate the association of neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and lymphocyte to monocyte ratio (LMR) with post-thrombolysis early neurological outcomes including early neurological improvement (ENI) and early neurological deterioration (END) in patients with acute ischemic stroke (AIS). Methods AIS patients undergoing intravenous thrombolysis were enrolled from April 2016 to September 2019. Blood cell counts were sampled before thrombolysis. Post-thrombolysis END was defined as the National Institutes of Health Stroke Scale (NIHSS) score increase of ≥ 4 within 24 h after thrombolysis. Post-thrombolysis ENI was defined as NIHSS score decrease of ≥ 4 or complete recovery within 24 h. Multinomial logistic regression analysis was performed to explore the relationship of NLR, PLR, and LMR to post-thrombolysis END and ENI. We also used receiver operating characteristic curve analysis to assess the discriminative ability of three ratios in predicting END and ENI. Results Among 1060 recruited patients, a total of 193 (18.2%) were diagnosed with END and 398 (37.5%) were diagnosed with ENI. Multinomial logistic model indicated that NLR (odds ratio [OR], 1.385; 95% confidence interval [CI] 1.238–1.551, P = 0.001), PLR (OR, 1.013; 95% CI 1.009–1.016, P = 0.001), and LMR (OR, 0.680; 95% CI 0.560–0.825, P = 0.001) were independent factors for post-thrombolysis END. Moreover, NLR (OR, 0.713; 95% CI 0.643–0.791, P = 0.001) served as an independent factor for post-thrombolysis ENI. Area under curve (AUC) of NLR, PLR, and LMR to discriminate END were 0.763, 0.703, and 0.551, respectively. AUC of NLR, PLR, and LMR to discriminate ENI were 0.695, 0.530, and 0.547, respectively. Conclusions NLR, PLR, and LMR were associated with post-thrombolysis END. NLR and PLR may predict post-thrombolysis END. NLR was related to post-thrombolysis ENI.

Background and Purpose: Symptomatic intracranial hemorrhage (sICH), potentially associated with poor prognosis, is a major complication of endovascular thrombectomy (EVT) for ischemic stroke patients. We aimed to develop and validate a risk model for predicting sICH after EVT in Chinese patients due to large-artery occlusions in the anterior circulation. Methods: The derivation cohort recruited patients with EVT from the Endovascular Treatment for Acute Anterior Circulation Ischemic Stroke Registry in China. sICH was diagnosed according to the Heidelberg Bleeding Classification within 24 hours of EVT. Stepwise logistic regression was performed to derive the predictive model. The discrimination and calibration of the risk model were assessed using the C index and the calibration plot. An additional cohort of 503 patients from 2 stroke centers was prospectively enrolled to validate the new model. Results: We enrolled 629 patients who underwent EVT as the derivation cohort, among whom 87 developed sICH (13.8%). In the multivariate adjustment, Alberta Stroke Program Early CT Score (odds ratio [OR], 0.85; P =0.005), baseline glucose (OR, 1.13; P =0.001), poor collateral circulation (OR, 3.06; P =0.001), passes with retriever (OR, 1.52; P =0.001), and onset-to-groin puncture time (OR, 1.79; P =0.024) were independent factors of sICH and were incorporated as the Alberta Stroke Program Early CT Score, Baseline Glucose, Poor Collateral Circulation, Passes With Retriever, and Onset-to-Groin Puncture Time (ASIAN) score. The ASIAN score demonstrated good discrimination in the derivation cohort (C index, 0.771 [95% CI, 0.716–0.826]), as well as the validation cohort (C index, 0.758 [95% CI, 0.691–0.825]). Conclusions: The ASIAN score reliably predicts the risk of sICH in Chinese ischemic stroke patients treated by EVT.

Background The trajectory of ischemic stroke patients attributable to large vessel occlusion is fundamentally altered by endovascular thrombectomy. This study aimed to develop a nomogram for predicting 3‐month mortality risk in patients with ischemic stroke attributed to artery occlusion in anterior circulation who received successful endovascular thrombectomy treatment. Methods and Results Patients with successful endovascular thrombectomy (modified Thrombolysis in Cerebral Infarction IIb or III) were enrolled from a multicenter registry as the training cohort. Step‐wise logistic regression with Akaike information criterion was utilized to establish the best‐fit nomogram. The discriminative value of the nomogram was tested by concordance index. An additional 224 patients from 2 comprehensive stroke centers were prospectively recruited as the test cohort for validating the new nomogram. Altogether, 417 patients were enrolled in the training cohort. Age (odds ratio [OR], 1.07; 95% CI, 1.03−1.10), poor pretreatment collateral status (OR, 2.13; 95% CI, 1.18−3.85), baseline blood glucose level (OR, 1.12; 95% CI, 1.04−1.21), symptomatic intracranial hemorrhage (OR, 9.51; 95% CI, 4.54−19.92), and baseline National Institutes of Health Stroke Scale score (OR, 1.08; 95% CI, 1.03−1.12) were associated with mortality and were incorporated in the nomogram. The c‐index of the nomogram was 0.835 (95% CI, 0.785–0.885) in the training cohort and 0.758 (95% CI, 0.667–0.849) in the test cohort. Conclusions The nomogram, composed of age, pretreatment collateral status, baseline blood glucose level, symptomatic intracranial hemorrhage, and baseline National Institutes of Health Stroke Scale score, may predict risk of mortality in patients with ischemic stroke and treated successfully with endovascular thrombectomy.

Cononsolvency of poly(N-isopropylacrylamide) (PNIPAM) gels in binary mixed solvents (water-acetone and water-DMSO) has been comparatively investigated by H HR-MAS NMR spectroscopy. The results demonstrate that, although the addition of both acetone and DMSO gives rise to cononsolvency behavior, PNIPAM preferentially interacts with acetone rather than DMSO in a water-rich regime, regardless of whether the temperature is above or below the volume phase transition temperature (VPTT). It suggests that the preferential adsorption of the additive cannot be deemed as a prerequisite for the cononsolvency in water-rich mixtures. The underlying molecular mechanism of cononsolvency involves a delicate balance between polymer-solvent and solvent-solvent interactions. Moreover, a new NOE-based NMR approach has been proposed to study the preferential adsorption in this work, which can be extensively adopted to study other relevant processes, including protein hydration, ligand binding, enzyme catalysis, etc.

Background and purpose Intravenous thrombolysis (IVT) has become the standard treatment for acute ischemic stroke within 4.5 hr after symptoms onset. However, a fraction of patients would develop early neurological deterioration (END) after IVT. The aim of our study was to explore the utility of neutrophil–lymphocyte ratio (NLR) in predicting END. Methods From October 2016 to March 2018, 342 consecutive patients with thrombolytic therapy were prospectively enrolled in this study. Blood cell counts were sampled in stroke emergency room before IVT. END was defined as a National Institutes of Health Stroke Scale score increase of ≥4 points within 24 hr after IVT. Multiple regression analysis was used to investigate the potential risk factors of END. We also performed receiver operating characteristic curve analysis and nomogram analysis to assess the overall discriminative ability of the NLR in predicting END. Results Of the 342 patients, 86 (25.1%) participants were identified with END. Univariate logistic regression analysis demonstrated that patients with NLR in the third tertile, compared with the first tertile, were more likely to have END (odds ratio, 9.783; 95% confidence interval [CI], 4.847–19.764; p = .001). The association remained significant even after controlled for potential confounders. Also, a cutoff value of 4.43 for NLR was detected in predicting post‐thrombolysis END with a sensitivity of 70.9% and a specificity of 79.3% (area under curve, 0.779; 95% CI, 0.731–0.822). Furthermore, our established nomogram indicated that higher NLR was an indicator of post‐thrombolysis END (c‐index was 0.789, p < .001). Conclusions This study showed that elevated level of NLR may predict post‐thrombolysis END in ischemic stroke patients.

The robust physisorption between nanoparticles (NPs) and proteins has attracted increasing attention due to the significance for both conjugation techniques and protein's corona formation at the bionano interface. In the present study, we first explored the possible binding sites of the bovine serum albumin (BSA) on amphiphilic polymer coated gold nanoparticles (AP-AuNPs). By using mass spectrometry, a 105-amino-acid peptide (12.2 kDa) is discovered as the possible "epitope" responsible for the robust physisorption between BSA and AP-AuNPs. Second, with the help of nanometal surface energy transfer (NSET) theory, we further found that the epitope peptide could insert at least 2.9 nm into the organic molecular layers of AP-AuNPs when the robust conjugates formed, which indicates how such a long epitope peptide can be accommodated by AP-AuNPs and resist protease's digestion. These findings might shed light on a new strategy for studying interactions between proteins and NPs, and further guide the rational design of NPs for safe and effective biomedical applications.

As a recently identified susceptibility gene for Alzheimer's disease (AD), triggering receptor expressed on myeloid cells 2 (TREM2) encodes an immune receptor that is uniquely expressed on microglia, functioning as a modulator of microglial functions including phagocytosis and inflammatory response. Several lines of evidence suggest that TREM2 is upregulated and positively correlates with tau pathology in the brains of AD patients. Meanwhile, our recent study showed that knockdown of TREM2 markedly exacerbated neuronal tau hyperphosphorylation in the brains of P301S-tau transgenic mice, implying that TREM2 might exert a protective role against tau pathology under AD context. However, the precise mechanisms underlying this observation remain largely unclear. In this study, by employing a microglial-neuronal co-culture model, we showed that microglial inflammatory response induced by lipopolysaccharide led to tau hyperphosphorylation in neurons via activation of a major tau kinase glycogen synthase kinase 3β, confirming the pathogenic effects of activated microglia on the progression of tau pathology. More importantly, by manipulating TREM2 levels in microglia with a lentiviral-mediated strategy, we demonstrated that TREM2 ameliorated the pathological effects of activated microglia on neuronal tau hyperphosphorylation via suppression of microglial inflammatory response. Taken together, these findings uncover the underlying mechanisms by which TREM2 protects against tau pathology and highlight TREM2 as a potential therapeutic target for AD.

Background and purpose Acute ischaemic stroke (AIS) is a vital cause of mortality and morbidity in China. Many AIS patients develop early neurological deterioration (END). This study aimed to construct a nomogram to predict END in AIS patients. Methods Acute ischaemic stroke patients in Nanjing First Hospital were recruited as the training cohort. Additional patients in Nantong Third People’s Hospital were enrolled as the validation cohort. Multivariate logistic regression was utilized to establish the nomogram. Discrimination and calibration performance of the nomogram were tested by concordance index and calibration plots. Decision curve analysis was employed to assess the utility of the nomogram. Results In all, 1889 and 818 patients were recruited in the training and validation cohorts, respectively. Age [odds ratio (OR) 1.075; 95% confidence interval (CI) 1.059–1.091], diabetes mellitus (OR 1.673; 95% CI 1.181–2.370), atrial fibrillation (OR 3.297; 95% CI 2.005–5.421), previous antiplatelet medication (OR 0.473; 95% CI 0.301–0.744), hyper‐sensitive C‐reactive protein (OR 1.049; 95% CI 1.036–1.063) and baseline National Institutes of Health Stroke Scale (OR 1.071; 95% CI 1.045–1.098) were associated with END and incorporated in the nomogram. The concordance index was 0.826 (95% CI 0.785–0.885) and 0.798 (95% CI 0.749–0.847) in the training and validation cohorts. By decision curve analysis, the model was relevant between thresholds of 0.06 and 0.90 in the training cohort and 0.08 and 0.77 in the validation cohort. Conclusions The nomogram composed of hyper‐sensitive C‐reactive protein, age, diabetes mellitus, atrial fibrillation, previous antiplatelet medication and baseline National Institutes of Health Stroke Scale may predict the risk of END in AIS patients.