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Introduction: Elevated circulatory concentrations of YKL-40 have been reported in patients with ischemic stroke. This study further investigated the association of plasma YKL-40 concentrations at admission and short, long-term prognosis after ischemic stroke. Methods: Based on a prospective, nationwide multicenter registry focusing consecutive patients of ischemic stroke and transient ischemic attack, plasma YKL-40 levels were detected by enzyme-linked immunosorbent assay at admission, and patients were stratified into percentile according to the plasma YKL-40 concentrations. The multivariate Cox or logistic regression model was used to investigate the association of YKL-40 concentration with death and functional outcomes at 3 months, 6 months, and 12 months after ischemic stroke, with potential confounders adjusted. Results: A total of 8,006 first-ever ischemic stroke patients, with the age of 61.7 ± 11.5, were included in this study. The mortality of 0–33%, 34–66%, 67–90%, and 91–100% groups at 12 months follow-up was 0.9%, 2.2%, 4.4%, and 9.4%, respectively (p < 0.0001), and the modified Rankin Scale 3–6 ratio was 6.8%, 10.5%, 15.7%, and 24.0%, respectively (p < 0.0001). In the multivariate regression, after adjusting for potential confounders, 91–100% group had higher risk of death (hazard ratio 2.99, 95% confidence interval 1.75–5.11)and modified Rankin Scale 3–6 (odds ratio 1.42, 95% confidence interval 1.08–1.88) at 12 months since onset of ischemic stroke compared to the 0–33% group. Conclusions: The elevated YKL-40 at admission can potentially help predict death, functional prognosis after ischemic stroke, which may help further studies to explore the potential physiological and pathological mechanism including the effects of vulnerable plaque and collateral circulation.

Sleep disorders are associated with cognitive impairments, greater amyloid-β (Aβ) burden and increased risk of developing Alzheimer's disease, while the underlying mechanism is unclear. N-methyl-d-aspartate receptors (NMDARs), as vital modulators of cognition, are sensitive to sleep disturbance. Sleep deprivation (SD) could induce the alterations of neuronal NMDAR subunits expression, however the alterations of astrocytic NMDARs in SD have not been reported. Our previous study has demonstrated knockdown of astrocytic Grin2a (gene encoding NMDAR subunit GluN2A) could aggravate Aβ-induced cognitive impairments, but what role astrocytic GluN2A may play in SD is unknown. Here we focused on the changes and roles of hippocampal astrocytic GluN2A in SD. Our results showed SD increased the expression of astrocytic GluN2A. Specific knockdown of hippocampal astrocytic Grin2a aggravated SD-induced cognitive decline, elevated Aβ, and attenuated the SD-induced increase in autophagy flux. Our finding, for the first time, revealed a novel neuroprotective role for astrocytic GluN2A in SD, which may be helpful for developing new preventive and therapeutic targets to sleep disorders.

Purpose This paper aims to focus on corporate social responsibility in relation to economic policy uncertainty in mergers and acquisitions (M&A). The following questions are addressed: How does policy uncertainty impact corporate M&A? Does social responsibility play a mediating role in this process? How does policy uncertainty affect corporate M&A through social responsibility? Design/methodology/approach This paper selects the major M&A events in China as the research object, and uses the Probit model to analyze the impact of policy uncertainty on M&A behavior and the business performance after the event, and further analyzes the internal mechanisms that cause these phenomena. Findings This paper shows that the higher the policy uncertainty, the lower the probability of a successful M&A, and the worse the business performance of the business after the event. Originality/value This paper provides useful reference for the study of M&A and social responsibility in different policy environments. At the same time, it provides direct empirical evidence to enhance the success rate of M&A.

This paper investigates the optimal strategies for an economic constrained closed-loop supply chain network. Manufacturers are classified into two categories namely low-emission manufacturers and high-emission manufacturers, and are subject to two greenhouse gas (GHG) emission control policies. Low-emission manufacturers are equipped with green production technologies to achieve ecological goals. All manufacturers are responsible in recycling and remanufacturing processes. New products and remanufactured products are homogeneous, and have the same sales price in the demand markets. Based on the variational inequality (VI) theory, we obtain the control equilibrium conditions of the non-cooperative game theory model for each firm. We further solve the model with the modified projection algorithm, and statically analyze and compare the influence of relevant parameters such as carbon quota, consumers’ low carbon preference and recovery rate on the network state through numerical examples. The results show that the GHG emission constraint may stimulate manufacturers to increase green technology investment level. Moreover, the introduction of reverse channel will promote resource recycling, but impair manufacturers’ profits. The promotion of consumer's environmental protection awareness has positive influence on the operation of supply chain network. In general, there is a conflict between economic goals and ecological ones. However, the developed model proves that economic goals and ecological ones can be realized consistently under certain conditions.

Background Tumor necrosis factor-induced protein 3 (A20) is a novel negative regulator of immunological homeostasis. This research aimed to determine whether A20 mRNA in peripheral blood mononuclear cells (PBMCs) could be used to predict 3-month functional outcome and mortality in individuals with acute cerebral infarction (ACI). Methods There were 50 healthy controls and 182 patients with ACI in this study. Real-time quantitative polymerase chain reaction was performed to detect the A20 mRNA expression levels in PBMCs from ACI patients and healthy controls.We also recorded the medical history, score of National Institutes of Health Stroke Scale score on the first day of disease onset (NIHSS1), cranial magnetic resonance imaging findings, and hematological examination index. On day 90 after disease onset, the prognosis was evaluated using a modified Rankin scale. Results In comparison to healthy controls, the median A20 mRNA levels in PBMCs of ACI patients were considerably greater (P P P

Since the production process in manufacturing industry is one of the main sources of carbon emissions, most governments have enacted relevant carbon policies to encourage manufacturers to invest in green production technology and reduce carbon emissions. However, the effectiveness of the carbon policy deserves further investigation because the manufacturers focus more on economic profits in actual operations. For this purpose, this paper proposes a dual-channel supply chain network (DCSCN) equilibrium model based on variational inequality theory to examine progressive carbon tax mechanism design of the government and its impacts on the production/pricing and abatement level decisions of the manufacturers in the DCSCN. In addition, this paper also examines the influences of the online channel introduction on supply chain network equilibrium decisions, carbon emissions and profits. We employ the modified projection and contraction algorithm to obtain the numerical solutions for several examples, and analyze the impacts of the key parameters on the equilibrium decisions and derive several managerial insights. The results show that if the government sets the high-level carbon tax and the cut-off value in progressive carbon tax policy appropriately, it can induce the manufacturers to improve abatement level actively; meanwhile the profit maximization goal of the manufacturer and the whole DCSCN can be consistent with the government's low-carbon emission target. Moreover, the introduction of online channel may depress the economic activities and lead to profit loss for the supply chain network but contributes to reducing the carbon emissions under progressive carbon tax policy. The conclusions may be useful for reference in the study of the low-carbon supply chain and the design of carbon emission reduction policy for government.

The association between haemoglobin A1c (HbA1c) and cerebral microbleeds (CMBs) remains unclear. We aimed to investigate the association between HbA1c and CMBs in community-based individuals without stroke or transient ischaemic attack (TIA) and whether the association differs between individuals with and without diabetes mellitus (DM).All individuals were recruited from a community in Beijing, China, from January 2015 to September 2019. All individuals completed a questionnaire and underwent blood tests and brain magnetic resonance imaging. A susceptibility-weighted imaging sequence was acquired to detect CMBs, which were defined as small, round and low-signal lesions with10 mm diameter. The association between HbA1c and CMBs was analysed using multivariable logistic regression adjusted for demographics, medical history and blood sample test results. Subgroup analyses stratified by history of DM were performed.Of 544 recruited individuals, 119 (21.88%) had CMBs. HbA1c was independently associated with CMBs (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.03-2.22). In 87 individuals with DM, multivariable logistic analysis showed that HbA1c was significantly associated with CMBs (OR, 1.67; 95% CI, 1.04-2.69), whereas in individuals without DM, no significant association was observed between HbA1c and CMBs (OR, 1.07; 95% CI, 0.50-2.30).HbA1c was associated with CMBs in individuals without stroke or TIA, particularly in individuals with DM, suggesting that the status of glycaemic control warrants attention for the prevention of CMBs. It would be beneficial to manage HbA1c specifically to control the risk of CMBs, especially in individuals with DM.

Numerous studies have examined the associations between air pollution and stroke. However, little is known about the associations between air pollution and transient ischemic attack (TIA). In this study, we aimed to conduct a time-series study to systematically examine the associations between hospital admissions for TIA and air pollutants. Admissions for TIA (ICD-10: G45) from 1 January 2014 to 31 December 2016 were identified based on the primary diagnosis from 134 hospitals in Beijing, China. Hourly measurements of air pollutants were obtained from the National Air Pollution Monitoring System. Generalized additive models with quasi-Poisson regression were used to determine the associations for each pollutant. Additionally, stratified analysis was implemented to examine whether age, gender, temperature, and season were the potential effect modifiers. Restricted cubic spline was applied to investigate the exposure-response curve. In total, 109,975 hospital admissions for TIA were included. The positive associations were detected between PM2.5, PM10, SO2, NO2, and CO and hospital admissions for TIA. The effects of PM2.5 and PM10 in men are stronger than in women. Additionally, the effects of PM2.5, PM10, SO2, and O3 are more pronounced on warm days than cool days. From exposure-response curves, we observe a nearly linear relationship for PM2.5, PM10, CO, and NO2. Further studies are needed to verify the association. This research contributes evidence on the association between air pollution and admissions for TIA in the low- and middle-income countries and may promote related public health policy development.

Expanding green consumption market and precise data promotion advantages make the platform economy have a significant effect on influencing manufacturers to carry out green R&D and production activities, and government subsidies have a positive incentive effect. In this context, for the studies about platform supply chain management with manufacturer’s green production and the platform’s marketing activities simultaneously are rare, we consider that a manufacturer invests in green technologies to produce products and sell them through a smart platform supply chain by an agency selling or reselling strategy, in which the platform provides data-driven marketing technology to promote green products. Four game models are constructed to study the operational efficiency of the platform supply chain considering selling strategy difference and government subsidy. The results show that: (1) The manufacturer’s green technology and the platform’s data-driven marketing levels, as well as all member’s profits are all influenced by the potential market demand of green products, the sensitivities of consumers to green product attributes, and data analysis technology. (2) The service commission rate charged by the platform plays a main role on the manufacturer’s selling strategy choice, when the service commission rate is low, the manufacturer chooses an agency selling strategy and can obtain more profit, but now the green technology level is not necessarily better than that in the reselling system. With the service commission rate increases, a manufacturer that chooses the reselling strategy can obtain more profit, and the green technology level is better than in the agency selling system. (3) Government subsidy can effectively encourage the manufacturer to improve the green technology level, and now the platform will improve the data-driven marketing level. There is a threshold range of the service commission rate charged by the platform in which the government can guide the manufacturer and the platform to reach an equilibrium selling strategy by regulating the subsidy level.

Guitao Zhang,1 Zixiao Li,1– 3 Hongqiu Gu,1– 3 Runhua Zhang,1,2 Xia Meng,1,2 Hao Li,1,2 Yilong Wang,1,2 Xingquan Zhao,1,2 Yongjun Wang,1– 6 Gaifen Liu1,2 On behalf of Chinese Stroke Center Alliance investigators1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3National Center for Healthcare Quality Management in Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Advanced Innovation Center for Human Brain Protection, Capital Medical University, Beijing, People’s Republic of China; 5Research Unit of Artificial Intelligence in Cerebrovascular Disease, Chinese Academy of Medical Sciences, Beijing, 2019RU018, People’s Republic of China; 6Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, People’s Republic of ChinaCorrespondence: Yongjun Wang; Gaifen Liu, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119 South Fourth Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86 10-59978350 ; +86 10-59976746, Email yongjunwang@ncrcnd.org.cn; liugaifen@ncrcnd.org.cnPurpose: To investigate the effectiveness of dysphagia screening and subsequent swallowing rehabilitation in elderly stroke patients with malnutrition risk.Patients and Methods: Based on the Chinese Stroke Center Alliance (CSCA) from August 1, 2015 to July 21, 2019, we compared the in-hospital adverse outcomes among stroke patients (including ischemic stroke, intracranial hemorrhage, and subarachnoid hemorrhage) over 70 years old with and without dysphagia screening. The primary outcome was in-hospital all-cause mortality. Secondary outcomes were the composite endpoint of discharge against medical advice (DAMA) or in-hospital death.Results: Among 365,530 stroke patients ≥ 70 years old with malnutrition risk in the CSCA, documented dysphagia screening was performed for 288,764 (79.0%) participants. Of these, 41,482 (14.37%) patients had dysphagia, and 33,548 (80.87%) patients received swallowing rehabilitation. A total of 1,694 (0.46%) patients experienced in-hospital death. After adjustment for traditional risk factors, dysphagia screening was associated with a low risk of all-cause mortality in stroke patients [adjusted odds ratio (aOR): 0.75, 95% confidence interval (CI):0.65– 0.87]. Compared to patients with dysphagia who did not receive swallowing rehabilitation, patients reveiving swallowing rehabilitation had a reduced risk of in-hospital death (aOR:0.39, 95% CI: 0.33– 0.46). Additionally, dysphagia screening had a lower risk for the composite endpoint of DAMA or in-hospital death (aOR:0.83,95% CI: 0.80– 0.87), as did subsequent swallowing rehabilitation (aOR:0.43,95% CI: 0.40– 0.47). Similar results were observed in the sensitivity analysis through inverse probability of treatment weighting, propensity score matching, and excluding patients without National Institutes of Health Stroke Scale scores. A similar association was observed between dysphagia management and adverse clinical outcomes in ischemic stroke and intracranial hemorrhage patients.Conclusion: Dysphagia screening and swallowing rehabilitation were associated with a reduced risk of in-hospital death and composite outcome of DAMA or in-hospital death for stroke patients with malnutrition risk. Future research should concentrate on improving the quality of medical care for dysphagia management to improve patients’ outcomes.Keywords: stroke, malnutrition risk, dysphagia screening, in-hospital death, discharge against medical advice

Rapid and accurate identification of the mechanisms of action (MoAs) of antibacterial compounds remains a challenge for the development of antibacterial compounds. Computational inference methods for determining the MoAs of antibacterial compounds have been developed in recent years. In particular, approaches combining machine learning technology enable precisely recognizing the MoA of antibacterial compounds. However, these methods heavily rely on the big data resulting from multiplexed experiments. As such, these approaches tend to produce minimal throughput and are not comprehensive enough to be adapted to widespread industrial applications. Here, we present a machine learning approach based on a customized array sensor for directly identifying the MoAs of antibacterial compounds. The array sensor consists of different two-dimensional nanomaterial fluorescence quenchers with different fluorescence-labeled single-stranded DNAs (ssDNAs). By mapping the subtle difference of the physicochemical properties on the bacterial surface treated with different antibacterial compound stimuli, the array sensor ensures visualizing the recognition process. Moreover, the customized array sensor produces a high volume of the MoA database, overcoming the dependence on big data. We further use the array sensor to build a chemical-response unique "fingerprint" database of MoAs. By combining a neural network-based genetic algorithm (NNGA), we rapidly discriminate the MoAs of four antibiotics with an overall accuracy of 100%. Furthermore, a new screening antibacterial peptide has been discovered and evaluated by our approach for determining the MoA with high accuracy proven by other techniques.

With the increasing popularity of ecological civilization and sustainable development, enterprises should consider environmental protection measures in their operations in addition to pursue their economic interests. This paper establsihes a closed-loop supply chain network model composed of multiple suppliers, manufacturers, retailers, recyclers, and demand markets—regarding their dual goals of the profit maximization and the minimization of carbon emissions. The conditions necessary for establishing overall equilibrium and an equilibrium model of the entire closed-loop supply chain network are determined by applying variational inequality and dual theory. A modified projection contraction algorithm is used to design a model-solving program. Finally, using numerical examples, the paper conducts a comparative static analysis on important parameters such as the weight coefficients of environmental protection objectives and consumers' awareness of low-carbon environmental protection and attains some beneficial enlightenment on management. The results indicate that when the environmental protection objectives of a certain type of enterprise increases, both the economic benefits and environmental protection performance will improve; when the environmental protection objectives of all enterprises increases simultaneously, environmental protection performance improves significantly, but the changes in economic benefits of different enterprises are inconsistent and profit coordination is more complex. Although consumers’ awareness of low-carbon preference could improve environmental performance, it reduces the overall profits of network members and the entire closed-loop supply chain network as a whole. The above conclusions can be used as a reference for the government in designing low-carbon environmental protection policy and in closed-loop supply chain research.

Feng Zhang,1 Tianrui Zhu,1 Heng Li,1 Yi He,2 Yuanyuan Zhang,1 Nana Huang,1 Guitao Zhang,3 Yanshuang Li,1 Dujuan Chang,1 Xiaohong Li1 1Department of Neurology, Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, The Second Affiliated Hospital of Xi’an Medical University, Xi’an, Shanxi, People’s Republic of China; 3Department of Neurology, Capital Medical University Affiliated Beijing Tiantan Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xiaohong Li Email xiaohong-li@sdu.edu.cnBackground: Interleukin-37 is a novel cytokine emerging as a natural suppressor of inflammatory responses. Inflammation and the immune response play important roles in acute ischemic stroke. This study aimed at evaluating the plasma levels and the association with 3-month outcomes of interleukin-37 in acute ischemic stroke patients.Patients and Methods: In total, 152 consecutive patients with acute ischemic stroke and 45 healthy controls were included. Plasma interleukin-37 levels were determined in the first morning after admission using an enzyme-linked immunesorbent assay. The primary outcome was the 3-month functional outcome (modified Rankin Scale score > 2). Logistic regression was used to evaluate the risk and 3-month outcome of stroke according to plasma interleukin-37 level.Results: Plasma interleukin-37 levels were significantly higher in the patients with acute ischaemic stroke than in the healthy controls (182.26 versus 97.89 pg/mL, p< 0.001). Patients with large-artery atherosclerosis had significantly higher IL-37 levels than those with small-artery occlusion (202.12± 35.82 versus 175.67± 33.71pg/mL, p< 0.001). Plasma interleukin-37 levels were positively correlated with National Institutes of Health Stroke Scale scores (r=0.521, p< 0.0001) and lesion volume (r=0.442, p< 0.0001). Ninety-four and 58 patients had favourable and unfavourable 3-month outcomes, respectively. Elevated plasma interleukin-37 levels were independently associated with unfavourable 3-month outcomes (adjusted odds ratio=1.033, p=0.001, 95% confidence interval: 1.015– 1.056).Conclusion: Admission plasma interleukin-37 levels were significantly increased after acute ischemic stroke. Elevated interleukin-37 levels were independently associated with unfavourable 3-month prognoses in acute ischemic stroke patients. Further studies with other populations are needed.Keywords: interleukin-37, acute ischemic stroke, functional outcome, prognosis

Few studies have applied the triglyceride, cholesterol, body weight index (TCBI) in acute ischemic stroke (AIS). We investigated the association between the TCBI and adverse clinical outcomes in patients with AIS.Based on the Third China National Stroke Registry (CNSR-III) data from August 2015 to March 2018, we evaluated the nutritional status of patients with AIS using the TCBI. Patients were categorized according to quartile levels of the TCBI. The main outcomes were poor functional outcomes and recurrent stroke at 1-year and secondary outcomes were adverse outcomes at 3 and 6 months after stroke onset. Poor functional outcomes consisted of all-cause mortality and major disabilities. Multivariate analyses with logistic or Cox regression analysis and restricted cubic splines determined the association between the TCBI and adverse outcomes. We included 9708 patients. At the 1-year follow-up, 1323 patients (13.6%) had died or experienced major disability. The adjusted odds ratios/hazard ratios and 95% confidence intervals of the lowest quartile at 1-year were 1.47 (1.22-1.78) for poor functional outcomes, 1.46 (1.18-1.81) for major disability, and 1.34 (0.94-1.86) for all-cause mortality. Kaplan-Meier analysis demonstrated an inverse relationship between all-cause mortality and the TCBI (log-rank p0.05). An approximately L-shaped relationship between TCBI levels and poor functional outcomes and major disability was observed at 1-year.The novel TCBI was associated with short- and long-term adverse outcomes in AIS. Thus, it may be useful for predicting adverse outcomes in patients with AIS.

Background and Purpose: To investigate the prevalence of malnutrition risk in patients with acute ischemic stroke (AIS) at admission, the association between malnutrition risk and long-term outcomes, and whether the predictive ability would be improved after adding to previous prognostic models for poor outcomes. Methods: Based on the Third China National Stroke Registry data from August 2015 to March 2018, we evaluated malnutrition risk using objective scores, including the controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index. The primary outcome was death or major disability (modified Rankin Scale score ≥3) at 1 year after stroke onset. We calculated the crude prevalence of malnutrition risk and investigated the association between malnutrition risk and clinical outcomes. Prognostic performance of 3 objective malnutrition scores for poor outcomes was assessed. Results: Moderate to severe malnutrition risk was identified in 5.89%, 5.30%, and 1.95% of the Third China National Stroke Registry AIS patients according to the controlling nutritional status score, geriatric nutritional risk index, and prognostic nutritional index, respectively. At 1-year follow-up, 1143 participants (13.5%) experienced death or major disability. After adjustment for traditional risk factors, moderate to severe malnutrition risk was associated with high risk of composite events (odds ratio, 2.25 [95% CI, 1.75–2.90], for controlling nutritional status score; odds ratio, 2.10 [95% CI, 1.63–2.69], for geriatric nutritional risk index; odds ratio, 3.36 [95% CI, 2.33–4.84], for prognostic nutritional index; all P P Conclusions: The prevalence of moderate or severe malnutrition risk in Chinese patients with AIS ranged from 1.95% to 5.89%. Malnutrition risk in patients with AIS was associated with increased risk of long-term death and major disability. Our study provides evidence supporting the prognostic significance of objective malnutrition scores after AIS.

Synapse degeneration correlates strongly with cognitive impairments in Alzheimer's disease (AD) patients. Soluble Amyloid‐beta (Aβ) oligomers are thought as the major trigger of synaptic malfunctions. Our earlier studies have demonstrated that Aβ oligomers interfere with synaptic function through N‐methyl‐D‐aspartate receptors (NMDARs). Our recent in vitro study found the neuroprotective role of astrocytic GluN2A in the promotion of synapse survival and identified nerve growth factor (NGF) derived from astrocytes, as a likely mediator of astrocytic GluN2A buffering against Aβ synaptotoxicity. Our present in vivo study focused on exploring the precise mechanism of astrocytic GluN2A influencing Aβ synaptotoxicity through regulating NGF. We generated an adeno‐associated virus (AAV) expressing an astrocytic promoter (GfaABC1D) shRNA targeted to Grin2a (the gene encoding GluN2A) to perform astrocyte‐specific Grin2a knockdown in the hippocampal dentate gyrus, after 3 weeks of virus vector expression, Aβ were bilaterally injected into the intracerebral ventricle. Our results showed that astrocyte‐specific knockdown of Grin2a and Aβ application both significantly impaired spatial memory and cognition, which associated with the reduced synaptic proteins PSD95, synaptophysin and compensatory increased NGF. The reduced astrocytic GluN2A can counteract Aβ‐induced compensatory protective increase of NGF through regulating pNF‐κB, Furin and VAMP3, which modulating the synthesis, mature and secretion of NGF respectively. Our present data reveal, for the first time, a novel mechanism of astrocytic GluN2A in exerting protective effects on synapses at the early stage of Aβ exposure, which may contribute to establish new targets for AD prevention and early therapy., Using a Grin2a (the gene encoding GluN2A) shRNA adeno‐associated viral (AAV) vector, an astrocyte‐specific Grin2a knockdown rat AD model was established. The results showed astrocytic Grin2a knockdown aggravated Aβ‐induced memory and cognitive deficits through modulating the synthesis, mature and secretion of NGF. This in vivo data reveal, for the first time, a novel mechanism of astrocytic GluN2A in exerting protective effects on synapses at the early stage of Aβ exposure.

This paper investigates the impacts of cap-and-trade (CAT) regulation on a three-echelon closed-loop supply chain network (CLSCN) that consists of suppliers, high-emission and low-emission manufacturers, demand markets and carbon trading centers. The presented CLSCN model includes both product trading and carbon trading subnets. Combining variational inequality theory (VI) with complementary theory, we first characterize the optimal conditions for members in each tier first, and then derive that of the entire CLSCN. In addition, we focus on the effects of carbon caps and EOL collection rate target on CLSCN performances with numerical examples. The results reveal that, in some cases, there is a consistency between carbon emission reduction target of the government and the profit target of enterprises. The government should choose reasonable and moderate carbon caps for all the enterprises to balance the CLSCN members’ economic interests, carbon emissions, as well as resources utilization rate. Moreover, the government should not blindly pursue a high collection rate target. The above conclusions can provide practical guidance for governments and enterprises in a CLSCN under CAT regulation.

AimTo investigate clinical characteristics, risk factors (RFs), neurologic deficits and medical care provided in children who had a stroke in China.MethodsWe conducted a retrospective case-series study using the medical records of children aged 1 month to 18 years with arterial ischaemic stroke (AIS) or haemorrhagic stroke (HS) (with the entry codes I60, I61, I62, I63 (ICD-10)), who were admitted to different hospitals in Beijing, between January 2018 and December 2018. We obtained the following information from the charts: demographic characteristics, clinical presentations, RFs for paediatric stroke, laboratory examination, neuroimaging records and neurologic sequelae.ResultsWe identified 312 first admissions for stroke (172 AIS and 140 HS). The mean age at onset was 8.6±3.9 years for patients who had an AIS and 8 (5–13) years for patients who had an HS. There were more males than females in both groups (AIS: 59.88% vs 40.12%; HS: 52.14% vs 47.86%). A known aetiology was identified in 92.44% and 86.43% of patients who had an AIS and HS, respectively. The leading cause of AIS was cerebrovascular diseases including moyamoya (68.6%), while that for HS was arteriovenous malformation (51.43%). The most common initial clinical presentation was hemiplegia (86.05%) in patients who had an AIS and headache (67.86%) in patients who had an HS. The use of healthcare, including acute treatment (antithrombotic in 17.44%, anticoagulant in 5.23%) and secondary prevention (antithrombotic in 6.39%, anticoagulant in 1.16%), varied and was significantly lower among patients who had an AIS. The most common complications were epilepsy (22.09%) and pneumonia (4.65%) in patients who had an AIS and epilepsy (17.14%) and hydrocephalus (12.14%) in patients who had an HS. Neurological deficits occurred in 62.8% of patients who had an AIS and 72.86% of patients who had an HS.ConclusionCerebral arteriopathy was a major RF for both AIS and HS in children living in China. Large epidemiological studies are required to identify RFs to prevent stroke as well as appropriate interventions.

Background: Alzheimer's disease (AD) is the most common neurodegenerative disorder that also involves neuroinflammation in addition to many other features. Icariin (ICA) as one of the active ingredients of Chinese herbal medicine has the immunomodulating function. This study aimed to investigate the immunotherapeutic potential of ICA on AD. Methods: APP/PS1 mice and wild type C57BL/6 mice were subjected to orally ICA administration (60 mg/kg/d) for 8 months. Then, the ethological and biochemical experiments, such as Morris water maze assay, Aβ ELISA, blood T cell flow cytometry, and plasma and brain cytokines array, were conducted to evaluate the effects of ICA administration. Results: ICA significantly improved spatial learning and memory retention in APP/PS1 mice. Long-term application of ICA could also reduce hippocampus Aβ deposition, modulate the differentiation of CD4+ T cells, and modulate the release of inflammatory cytokines in plasma and brain tissue. Conclusion: ICA shows the neuroprotective effects via modulating the CD4+ T lymphocyte-related immuno-inflammatory responses in APP/PS1 mice and may be a promising drug against AD progression.

Aim: YKL-40 is a novel biomarker that is associated with both acute and chronic inflammations. Elevated plasma concentrations of YKL-40 have been reported in patients with ischemic stroke. This study investigated the association of plasma YKL-40 concentrations at admission and short, long-term prognosis after ischemic stroke. Methods: This study is a prespecified biomarker sub-study of the third China National Stroke Registry (CNSR3), which is a prospective,national multi-center of 171 sites concerning consecutive patients of ischemic stroke and TIA within 7 days since onset with specimens collected at baseline. Plasma YKL-40 levels were detected by ELISA and patients were stratified into terciles according to Plasma YKL-40 concentrations. The multivariate Cox regression model was used to investigate the association of YKL-40 concentration and death and recurrence at 3 months, 6 months and 12 months after ischemic stroke, with potential confounders adjusted. Results: A total of 8013 first-ever ischemic stroke patients, with an average of 61.7±11.5 years, were included in this study. The YKL-40 concentrations of lower, middle and upper group were 30.36 ±8.53 mg/L, 64.89±13.49 mg/L, and 164.42±50.35 mg/L respectively. Higher YKL-40 concentration at admission was associated with combination events of death and recurrence, death as well as recurrence at 3-month, 6-month and 12-month since onset of ischemic stroke when compared with lower YKL-40 concentration. However, after adjusting for age, gender, smoking, drinking, hypertension, diabetes, low-density lipoprotein, and C-reactive protein, higher YKL-40 concentration at admission was just statistically associated with combination events and death, but not stroke recurrence at 3-month, 6-month and 12-month when compared with lower YKL-40 concentration (table 1). Conclusions: The elevated YKL-40 at admission was associated with short and long-term death, but not recurrence after ischemic stroke.

The development of noble-metal-free single atom electrocatalysts (SAECs) with both remarkable activity and durability for oxygen reduction reaction (ORR) are in great demand for large-scale commercialization of proton-exchange membrane fuel cells and metal-air batteries. Here, we developed a novel strategy to fabricate high-performance Cu-SAs/NSs from pyrolysis of two-dimensional (2D) Cu/Zn bimetallic MOF. Specifically, nitrogen-rich molecules (melamine) were deliberately added to intrigue the self-assembly of Cu/Zn bimetallic MOF, and contribute to the formation of highly porous structure and abundant Cu-N4 active sites. With the enhanced accessibility of active sites and mass transport, the as-developed Cu-SAs/NSs display a remarkable ORR performance in alkaline media, outperforming the benchmark Pt/C and most of platinum group metals (PGMs)-free electrocatalysts reported to date. Notably, this facile strategy can be extended to fabricate other transition metal (TM, TM = Fe, Co, Ni)-based single atoms. This work presents a novel and general strategy to construct carbon-based SAECs towards ORR.

Background：Urinary retention is a general and serious refractory complication after spinal cord injury (SCI). However, effective therapeutic approaches remain limited. Previous clinical and animal research have clarified that acupuncture could be beneficial to the recovery of bladder function, however, most of the previous trials are of low quality and high-quality studies are still necessary.Methods: Here, we conduct a study design and protocol of a randomized, blinded, controlled study to evaluate the efficacy and safety of electroacupuncture at the “Four Abdominal and Sacral Acupoints” for urinary retention after SCI. A total of 90 patients with residual urine above 300ml will be recruited in the trial and randomized into treatment group or control group. Patients in the treatment group will receive Electroacupuncture at the “Four Abdominal and Sacral Acupoints” combined with conventional treatment while patients in the control group will receive conventional treatment alone for 4 weeks. The primary outcomes are changes of residual urine volume at baseline, after the final treatment and 4 weeks after the final treatment. The secondary outcome measures will be the proportions of participants with residual urine decline≥50% and efficacy rate after 4 weeks’ treatment, as well as the proportion of patients with catheterization, Short-Form Health Survey Questionnaire (SF-36) and the incidence of symptomatic urinary tract infection at baseline, after the final treatment and 4 weeks after the final treatment. The safety will also be assessed by monitoring the incidence of adverse events and changes in vital signs during the study.Discussion：Results from this trial will significantly support the application of electroacupuncture in the recovery of bladder function after SCI. If found to be effective and safe, electroacupuncture will be a valuable complementary option for patients with urinary retention after SCI.Trial registration: Chinese Clinical Trial Registry: ChiCTR 1900022089. Registered on 24 March 2019, http://www.chictr.org.cn/showproj.aspx?proj=37161.

Background: There is some controversy whether stroke history is an independent risk factor for poor prognosis of stroke or not. This study aimed to investigate the difference of mortality, disability and recurrent rate of ischemic stroke patients without and with stroke history, as well as to explore the effect of stroke history on stroke prognosis. Methods: We analyzed patients with ischemic stroke enrolled in the China National Stroke Registry which was a nationwide, multicenter, and prospective registry of consecutive patients with acute cerebrovascular events from 2007 to 2008. Multivariable logistic regression was performed to assess the risk of worse prognosis of stroke history in patients with ischemic stroke. Results: A total of 8181(65.9%) patients without stroke history and 4234(34.1%) patients with stroke history were enrolled in the study. The mortality, recurrence, modified Rankin Scale (mRS) 3-6 rate was 11.4%, 14.7% and 28.5% respectively at 1 year for patients without stroke history, which was significantly lower than that of 17.3%, 23.6%, 42.1% in patients with stroke history, respectively. Multivariable analysis showed that patients with stroke history had higher risk of death [odds ratio (OR) 1.34,95% confidence interval (CI) 1.17-1.54], recurrence (OR 1.47, 95 % CI 1.31-1.65) and mRS 3-6 (OR 1.49,95% CI 1.34-1.66) at 1 year. Conclusion: After adjusting for the potential confounders, stroke history was still an independent risk factor for poor prognosis of ischemic stroke, which further emphasizes the importance of secondary prevention of ischemic stroke. The specific causes of poor prognosis in patients with history of stroke need to be furtherly investigated.

Background: For patients hospitalized after acute ischemic stroke (AIS), the preadmission comorbidities, level of consciousness (LOC), age and neurologic deficit (PLAN) score can help to identify those who may have a poor outcome. Implementing the PLAN score in other types of stroke may also have predictive value. Our study aimed to evaluate the PLAN score’s prognostic accuracy in predicting 1-year mortality and severe disability after intracerebral hemorrhage (ICH). Methods: We analyzed data found in the China National Stroke Registry (CNSR) of 2,453 hospitalized patients in 132 urban Chinese hospitals, diagnosed with ICH from September 2007 to August 2008. The outcomes analysis included 30-day mortality, modified Rankin Scale score (mRS) of 5–6 at discharge, and 1-year mortality. Univariate and multivariate analysis was performed, and we calculated consistency statistics (C statistic). We evaluated the PLAN score performance using area under the curve (AUC) calculations. Results: We found that the 30-day mortality was 12.6%, the frequency of a mRS 5–6 at discharge was 20.6%, and 1-year mortality was 21.9%. The PLAN score had good predictive value in 30-day mortality (C statistic, 0.82), death or severe dependence at discharge (0.84), and 1-year mortality (0.82). Conclusions: In patients hospitalized for ICH, the 30-day mortality, death or severe dependence at discharge and 1-year mortality can be predicted by the PLAN score. Similarly to patients hospitalized after AIS, the PLAN score can help to identify patients likely to have poor outcomes following hospitalization for ICH.

Alzheimer's disease (AD) is an inexorable neurodegenerative disease that involves neuroinflammation in the brain, in addition to abnormal accumulation of amyloid-β (Aβ) and hyperphosphorylated tau. Evidence shows that human cord blood-derived multipotent stem cells (CB-SCs) can modulate autoimmune responses by altering regulatory T cells (Tregs). Our previous study found that CB-SCs could regulate the peripheral immune system of AD patients in vitro, mainly increasing the proportion of Tregs and anti-inflammatory cytokines. To further investigate the effects of lymphocytes co-cultured with CB-SCs on AD, the APP/PS1 mice received monthly transplants of lymphocytes co-cultured with CB-SCs for 4 months. Then, the ethological and biochemical experiments were conducted. We found that APP/PS1 mice injected with lymphocytes co-cultured with CB-SCs showed improved spatial learning, which significantly correlated with fewer Aβ plaques in brain. The present study also indicated that lymphocytes co-cultured with CB-SCs could promote the protective and reparative cytokines in the peripheral blood and brain to alleviate neuroinflammation in AD mice. These findings conclude that the systemic transplantation of lymphocytes co-cultured with CB-SCs can improve cognitive and pathological impairment of APP/PS1 mice via an immunomodulatory effect.

Background: Traumatic brain injury (TBI) has become a major cause of morbidity and mortality both in China and abroad. Disorders of consciousness following severe TBI is a common refractory complication, resulting in difficult rehabilitation and poor life quality. However, effective therapeutic approaches remain limited. Although acupuncture has been widely applied in the treatment of neurological disorders in China, its efficacy and safety for consciousness recovery remain to be elucidated. Methods: Here, we conduct a study design and protocol of a randomized, blinded, controlled study to evaluate the efficacy and safety of electroacupuncture at auricular acupoints “heart” and “brainstem” combined with body acupuncture in the consciousness recovery of patients with TBI. A total of 80 patients with initial Glasgow coma scale score between 3 and 8 points will be recruited in the trial and randomized into intervention (combined application of auricular electroacupuncture and body acupuncture) group or control (conventional treatment) group. Patients in the intervention group will receive electroacupuncture at bilateral auricular acupoints “heart” and “brainstem” (4 points in total) combined with body acupuncture in addition to conventional treatment while patients in the control group will receive conventional treatment alone for 8 weeks. The primary outcomes are changes of Glasgow coma scale score and mismatch negativity of event-related brain potentials at baseline after 4 weeks after the final treatment and 4 weeks after the final treatment. The secondary outcome measures will be changes of Barthel and FuglMeyer scores at baseline after 4 weeks after the final treatment and 4 weeks after the final treatment. The safety will also be assessed by monitoring the incidence of adverse events and changes in vital signs during the study. Discussion: Results from this trial will significantly support the application of auricular acupuncture and body acupuncture in the consciousness recovery of patients with severe TBI. If found to be effective and safe, auricular acupuncture combined with body acupuncture will be a valuable complementary option for comatose patients with TBI. Trial registration: Chinese Clinical Trial Registry: ChiCTR1800020245. Registered on 21 December 2018.

Background Studies have shown that psychosocial stress is involved in Alzheimer's disease (AD) pathogenesis; it induces M1 microglia polarization and production of pro-inflammatory cytokines, leading to neurotoxic outcomes and decreased β-amyloid (Aβ) clearance. Icariin has been proven to be an effective anti-inflammatory agent and to activate peroxisome proliferator-activated receptors gamma (PPARγ) which induces the M2 phenotype in the microglia. However, whether restraint/isolation stress reduces the clearance ability of microglia by priming and polarizing microglia to the M1 phenotype, and the effects of icariin in attenuating the inflammatory response and relieving the pathological changes of AD are still unclear. Methods APP/PS1 mice (male, aged 3 months) were randomly divided into a control group, a restraint/isolation stress group, and a restraint/isolation stress + icariin group. The restraint/isolation stress group was subjected to a paradigm to build a depressive animal model. Sucrose preference, open field, elevated plus maze, and Y maze test were used to assess the stress paradigm. The Morris water maze test was performed to evaluate spatial reference learning and memory. Enzyme-linked immunosorbent assay and immunohistochemistry were used to identify the microglia phenotype and Aβ accumulation. Western blotting was used to detect the expression of PPARγ in the hippocampus and prefrontal cortex (PFC). Results Restraint/isolation stress induced significant depressive-like behaviors in APP/PS1 mice at 4 months of age and memory impairment at 10 months of age, while 6 months of icariin administration relieved the memory damage. Restraint/isolation stressed mice had elevated pro-inflammatory cytokines, decreased anti-inflammatory cytokines, increased Aβ plaque accumulation and more M1 phenotype microglia in the hippocampus and PFC at 10 months of age, while 6 months of icariin administration relieved these changes. Moreover, restraint/isolation stressed mice had down-regulated PPARγ expression in the hippocampus and PFC at 10 months of age, while 6 months of icariin administration reversed the alteration, especially in the hippocampus. Conclusion Restraint/isolation stress induced depressive-like behaviors and spatial memory damage, over-expression of M1 microglia markers and more severe Aβ accumulation by suppressing PPARγ in APP/PS1 mice. Icariin can be considered a new treatment option as it induces the switch of the microglia phenotype by activating PPARγ.

This paper considers a dual-channel supply chain network consisting of multiple competing manufacturers, multiple competing retailers and multiple demand markets. Each manufacturer produces and distributes his products via direct e-commerce channel along with traditional physical channel. The manufacturers also provide services for the consumers in both channels, while the retailers only offer offline services to the consumers. On this basis, a dual-channel supply chain network equilibrium model with pricing and service decisions are established based on variational inequality theory. Nash equilibrium solutions are obtained by modified projection and contraction method. Combined with numerical examples, we analyze the impact of three critical factors on the equilibrium states and profits. Some interesting managerial insights are derived. We find that the profits of the manufacturers decrease (increase) in the raw material conversion ratio under single channel case (dual-channel case), while the increase of the raw material conversion ratio always benefits the retailers and the whole dual-channel supply chain network; the service level in each channel is positively correlated with its transaction volume. There are significant inconsistencies among the best combinations of cross-channel price coefficients between two channels for the manufacturers, the retailers and the whole dual-channel supply chain network. The same equilibrium decision (service level, price) or profit may exhibit the opposite changing trend with respect to cross-channel price coefficients under two cases of active e-commerce transaction and inactive e-commerce transaction. When the introduction of e-commerce channel can bring more profits for the whole dual-channel supply chain network, the manufacturers should provide reasonable allocation schemes of profit increment for the retailers to satisfy their participation constraints.

Preclinical and clinical trails show that c-kitc-Kitc-KitThe results suggest that transient treatment with BMP-2 can induce c-kit

Nasopharyngeal carcinoma (NPC) is a common disease among southern Chinese. The major etiological factors proposed for NPC pathogenesis include genetic susceptibility, environment factors and EBV infection. In the high risk population, genetic susceptibility to NPC has been mapped to the HLA loci and adjacent genes in MHC region on chromosome 6p21. Consumption of preserved food including salted fish has been implicated in its etiology in earlier studies. Its contribution to pathogenesis of NPC remains to be determined. A decreasing trend of NPC incidence was observed in Hong Kong, Taiwan and Singapore in recent years which may be accounted by a change of dietary habits. A comprehensive epidemiological study will help to elucidate the relative importance of various risk factors in the pathogenesis of NPC. Despite the close association of EBV infection with NPC, the etiological role of EBV in NPC pathogenesis remains enigmatic. EBV infection in primary nasopharyngeal epithelial cells is uncommon and difficult to achieve. EBV does not transform primary nasopharyngeal epithelial cells into proliferative clones, which contrasts greatly with the well-documented ability of EBV to transform and immortalize primary B cells. Genetic alterations identified in premalignant nasopharyngeal epithelium may play crucial roles to support stable EBV infection. Subsequently, latent and lytic EBV gene products may drive clonal expansion and transformation of premalignant nasopharyngeal epithelial cells into cancer cells. Stromal inflammation in nasopharyngeal mucosa is believed to play an important role in modulating the growth and possibly drive the malignant transformation of EBV-infected nasopharyngeal epithelial cells. Furthermore, there are increasing evidences supporting a role of EBV infection to evade host immune surveillance. EBV-infected cells may have selective growth advantages in vivo by acquiring a stress-resistance phenotype. Understanding the etiological factors and pathogenesis of NPC will contribute effectively to the prevention and treatment of this disease.

Background:Hemiplegic shoulder pain (HSP) is a frequent complication after stroke and limits patients’ physical functioning of the affected arm, thus compromising their quality of life. Fu's subcutaneous needling (FSN) has been widely applied in the treatment of pain diseases in China; howev

A flexible acoustic emission (AE) sensor based on lead zirconate titanate (PZT) nanofiber composite membrane is described. The PZT nanofibers, with diameters varying from 50 nm to 120 nm, were electrospun and aligned across interdigitated electrodes. After being packaged in a flexible polymer structure with a thickness of ∼5 μm, this small scale AE sensor can bend freely to follow curved surfaces or embedded into structures. High piezoelectric voltage constant, flexibility and mechanical strength of PZT nanfibers result in a high performance of the demonstrated AE sensor. Fundamental characterization indicates a spontaneous polarization of the PZT nanofibers without any polarization treatment. The electromechanical coupling effect was increased up to 370% after 90 min of polarization under an external electric field of ∼3 V/μm. The anisotropic sensitivity, which can reduce the required number of sensors to indentify the location of the AE source, was observed from the attenuation maps. The small scale, flexible and highly sensitive PZT nanofiber AE sensor opens up new applications for monitoring small scale structures, curved surfaces and even living cells.

A microelectro-mechanical (MEMS) tester that can be used to measure the thermal conductivity of nanowires and nanostrips has been developed. Error analysis showed our measurements were accurate within 21%. This device has a low fabrication requirement so that it can be made in most MEMS laboratories. To verify the function of this device, the thermal conductivity of a carbon nanofiber with a diameter of 225 nm was measured to be 14.7 ± 3.1 Wm −1 K −1 , which is close to the value previously reported. This result was within the predicted measurement error and it proves that this device can be an effective tool for the research of nanostructures’ heat transfer, especially for nano-thermoelectrics.