HRD1-mediated METTL14 degradation regulates m6A mRNA modification to suppress ER proteotoxic liver disease.

Accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER) lumen triggers an unfolded protein response (UPR) for stress adaptation, the failure of which induces cell apoptosis and tissue/organ damage. The molecular switches underlying how the UPR selects for stress adaptation over apoptosis remain unknown. Here, we discovered that accumulation of unfolded/misfolded proteins selectively induces N6-adenosine-methyltransferase-14 (METTL14) expression. METTL14 promotes C/EBP-homologous protein (CHOP) mRNA decay through its 3' UTR N6-methyladenosine (m6A) to inhibit its downstream pro-apoptotic target gene expression. UPR induces METTL14 expression by competing against the HRD1-ER-associated degradation (ERAD) machinery to block METTL14 ubiquitination and degradation. Therefore, mice with liver-specific METTL14 deletion are highly susceptible to both acute pharmacological and alpha-1 antitrypsin (AAT) deficiency-induced ER proteotoxic stress and liver injury. Further hepatic CHOP deletion protects METTL14 knockout mice from ER-stress-induced liver damage. Our study reveals a crosstalk between ER stress and mRNA m6A modification pathways, termed the ERm6A pathway, for ER stress adaptation to proteotoxicity.

10-year Temporal Trends of Intravenous Thrombolysis in Acute Ischemic Stroke: Analysis of the China National Stroke Registry I-â ¢.

OBJECTIVES: To investigate the 10-year trend in healthcare quality of intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator in acute ischemic stroke (AIS) in China. MATERIALS AND METHODS: We analyzed 42,188 AIS within 7 days of onset from the China National Stroke Registry (CNSR) Ⅰ-Ⅲ. Primary outcomes were temporal changes in the proportion of patients arriving at the hospital within 3.5 hours (and 2 hours) of onset and receiving IVT within 4.5 hours (and 3 hours), stratified by region and hospital tier. Secondary outcomes included temporal changes in door-to-needle time (DNT), DNT ≤60 min and favorable outcome defined as a 90-day modified Rankin Scale (mRS) of 0-1. RESULTS: Among patients arriving at the hospital within 3.5 hours of onset, 13.5%, 7.1% and 33.4% patients received IVT within 4.5 hours in CNSR Ⅰ, Ⅱ and Ⅲ, respectively, including a higher proportion from eastern China (37.0%) and tertiary hospitals (36.5%). The median DNT was shorter in CNSR Ⅲ (60.0 min) than those in Ⅱ (95.0 min) and I (94.0 min). The proportion of patients with DNT ≤60 min was greater in Ⅲ (53.4%) than those in Ⅱ (26.7%) and Ⅰ (13.4%). The proportion of favorable outcomes was higher in CNSR Ⅲ (72.8%) than those in Ⅱ (49.6%) and Ⅰ (49.4%). Similar trends were observed for patients arriving at the hospital within 2 hours and receiving IVT within 3 hours of onset. CONCLUSIONS: The healthcare quality of IVT has improved remarkably in the past decade, notably in eastern China and tertiary hospitals.

The cGAS-STING pathway: The role of self-DNA sensing in inflammatory lung disease.

The presence of DNA in the cytosol is usually a sign of microbial infections, which alerts the host innate immune system to mount a defense response. Cyclic GMP-AMP synthase (cGAS) is a critical cytosolic DNA sensor that elicits robust innate immune responses through the production of the second messenger, cyclic GMP-AMP (cGAMP), which binds and activates stimulator of interferon genes (STING). However, cGAS binds to DNA irrespective of DNA sequence, therefore, self-DNA leaked from the nucleus or mitochondria can also serve as a cGAS ligand to activate this pathway and trigger extensive inflammatory responses. Dysregulation of the cGAS-STING pathway is responsible for a broad array of inflammatory and autoimmune diseases. Recently, evidence has shown that self-DNA release and cGAS-STING pathway over-activation can drive lung disease, making this pathway a promising therapeutic target for inflammatory lung disease. Here, we review recent advances on the cGAS-STING pathway governing self-DNA sensing, highlighting its role in pulmonary disease.

Age-Dependent Differences in T-Cell Responses to Influenza A Virus.

Respiratory infections from influenza A virus (IAV) cause substantial morbidity and mortality in children relative to adults. T cells play a critical role in the host response to IAV by supporting the innate and humoral responses, mediating cytotoxic activity, and promoting recovery. There are age-dependent differences in the number, subsets, and localization of T cells, which impact the host response to pathogens. In this article, we first review how T cells recognize IAV and examine differences in the resting T-cell populations between juveniles and adults. Next, we describe how the juvenile CD4+, CD8+, and regulatory T-cell responses compare with those in adults and discuss the potential physiologic and clinical consequences of the differences. Finally, we explore the roles of two unconventional T-cell types in the juvenile response to influenza, natural-killer T cells and γδ T cells. A clear understanding of age-dependent differences in the T-cell response is essential to developing therapies to prevent or reverse the deleterious effects of IAV in children.

Influence of gene modification in biological behaviors and responses of mouse lung telocytes to inflammation.

BACKGROUND: Telocytes play key roles in maintenance of organ/tissue function and prevention of organ injury. However, there are great challenges to investigate telocytes functions using primary telocytes, due to the difficulties of isolation, identification, and stability. The present study aims at constructing continuous cell strain of mouse lung telocyte cell line with stable characters by gene modification and investigating biological behaviors and responses of gene-modified telocytes to inflammation. METHODS: Mouse primary lung telocytes were isolated and identified using immune-labeling markers and immunoelectron microscopy. Primary telocytes were transformed with Simian vacuolating virus 40 small and large T antigen (SV40). Biological characters, behaviors morphology, and proliferation of those gene-modified telocytes were defined and monitored dynamically for 50 generations, as compared with primary lung telocytes. Cell cycle of mouse primary lung telocytes or gene-modified telocytes was detected by flow cytometry. RESULTS: Gene modified telocytes of generations 5, 10, 30 and 50 were observed with telopodes and also showed CD34 and ckit positive. Multiple cellular morphology were also observed on telocyte cell-line under monitor of celliq and enhanced cell proliferation were showed. SV40 transduction was also reduced apoptosis and increased the ratio of S and G2 phases in telocyte cell-line. CONCLUSION: We successfully constructed mouse lung telocyte cell-line which maintained the biological properties and behaviors as primary telocytes and could responses to inflammation induced by LPS. Thus, gene-modified lung telocytes, Telocyte Line, would provide a cell tool for researchers exploring the roles and applications of telocytes involved in physiological and pathological states in future.

Telocytes promote VEGF expression and alleviate ventilator-induced lung injury in mice.

Mechanical ventilation (MV) is an important procedure for the treatment of patients with acute lung injury or acute respiratory distress syndrome in a clinical setting; however, MV can lead to severe complications, including ventilator-induced lung injury (VILI). Telocytes (TCs) can promote tissue repair following injury in the heart, kidneys, and other organs. The aim of this study was to investigate the role of TCs in VILI in mice and the associated mechanisms. By using in vivo studies in mice and in vitro studies in cells, we demonstrated that an airway injection of TCs can reduce the pulmonary inflammatory response and improve the lung function in mice with VILI and promote the proliferation of pulmonary vascular endothelial cells. We also demonstrated that the impact of TCs on VILI repair might partially due to vascular endothelial growth factor (VEGF) secreted by TCs upon VILI stimulation, and that VEGF could induce the proliferation of hemangioendothelioma endothelial cells (EOMA). Collectively, our results revealed novel functions of TCs in VILA repair and shed light on the complications that are caused by MV.

Brief Report: Human Mesenchymal Stem-Like Cells Facilitate Floating Tumorigenic Cell Growth via Glutamine-Ammonium Cycle.

How mesenchymal stem cells (MSCs) promote tumor growth remains incompletely understood. Here, we show that mesenchymal stem-like cells (MSLCs) are commonly present in malignant pleural effusion or ascites of cancer patients, where they directly interact with tumor cells. Chemokines and chemokine receptors, especially the CCL2/CCR2 pathway, are involved in this interaction. As a result, MSLCs exert tumor-promoting effects by enhancing the proliferation and colony formation of tumor-repopulating cells. The underlying molecular basis involves MSLC release of glutamine to tumorigenic cells. Inhibition of glutamine uptake impedes MSC-mediated tumor-promoting effects. More intriguingly, MSLCs take up tumor cell-released ammonium that, in turn, favors MSLC growth. Thus, glutamine and ammonium form a vicious cycle between MSLCs and tumorigenic cells. These findings suggest a potential clinical application by targeting MSLCs in patients with malignant pleural effusions or ascites.

PbS/CsPbBr3 Heterojunction for Broadband Neuromorphic Vision Sensing.

Neuromorphic light sensors with analogue-domain image processing capability hold promise for overcoming the energy efficiency limitations and latency of von Neumann architecture-based vision chips. Recently, metal halide perovskites, with strong light-matter interaction, long carrier diffusion length, and exceptional photoelectric conversion efficiencies, exhibit reconfigurable photoresponsivity due to their intrinsic ion migration effect, which is expected to advance the development of visual sensors. However, suffering from a large bandgap, it is challenging to achieve highly tunable responsivity simultaneously with a wide-spectrum response in perovskites, which will significantly enhance the image recognition accuracy through the machine learning algorithm. Herein, we demonstrate a broadband neuromorphic visual sensor from visible (Vis) to near-infrared (NIR) by coupling all-inorganic metal halide perovskites (CsPbBr3) with narrow-bandgap lead sulfide (PbS). The PbS/CsPbBr3 heterostructure is composed of high-quality single crystals of PbS and CsPbBr3. Interestingly, the ion migration of CsPbBr3 with the implementation of an electric field induces the energy band dynamic bending at the interface of the PbS/CsPbBr3 heterojunction, leading to reversible, multilevel, and linearly tunable photoresponsivity. Furthermore, the reconfigurable and broadband photoresponse in the PbS/CsPbBr3 heterojunction allows convolutional neuronal network processing for pattern recognition and edge enhancements from the Vis to the NIR waveband, suggesting the great potential of the PbS/CsPbBr3 heterostructure in artificial intelligent vision sensing.

Airborne spread and infection of a novel swine-origin influenza A (H1N1) virus.

BACKGROUND: The novel swine-origin influenza A (H1N1) virus (S-O 2009 IV) can cause respiratory infectious diseases in humans and pigs, but there are few studies investigating the airborne spread of the virus. In January 2011, a swine-origin H1N1 epidemic emerged in eastern China that rapidly spread to neighboring farms, likely by aerosols carried by the wind. METHODS: In this study, quantitative reverse transcription polymerase chain reaction (RT-PCR) was used to detect viruses in air samples from pig farms. Based on two aerosol infection models (Pig and guinea pig), we evaluated aerosol transmission and infection of the novel S-O 2009 IV isolate. RESULTS: Three novel S-O 2009 IV were isolated from the diseased pig. The positive rate and viral loads of air samples were 26.1% and 3.14-5.72 log10copies/m³ air, respectively. In both pig and guinea pig infection models, the isolate (A/swine/Shandong/07/2011) was capable of forming aerosols and infected experimental animals at a range of 2.0-4.2 m by aerosols, but aerosol route was less efficient than direct contact. CONCLUSIONS: The results indicated that S-O 2009 IV is able to be aerosolized by infected animals and to be transmitted to susceptible animals by airborne routes.

Analysis of the rule of window-to-wall ratio on energy demand of residential buildings in different locations in China.

Building energy demands are influenced by the window-to-wall ratio (WWR). The impact of the WWR on the energy demand in the same area has been researched by software. However, the impact of the WWR on the energy demand of buildings in different locations of China has not been investigated using the energy balance equation. The equation for the indoor temperature variation under various internal and external disturbances was provided in this study. The relationship between parameters A and B and the change in indoor temperature was proven. China's Harbin, Beijing, and Chengdu air-conditioning and heating loads, as well as the impact of changing WWR on the rate of energy savings for air-conditioning and heating energy demand, were studied. After investigating the changes in the cooling and heating loads in various cities under various WWRs, the suitable relationship between the cooling and heating loads and the WWR of three urban units was discovered. The findings indicated that despite the three cities' various climates and the diverse energy demands for air conditioning and heating in each city, with the same change in the WWR of urban buildings, the change rate of the air conditioning and heating loads in each city was near. Meanwhile, the heating and cooling loads were linear with WWR.

White matter abnormalities are associated with the declined ability of reasoning and problem-solving in major depressive disorder.

OBJECTIVES: Executive function in people with depression is linked to the integrity of white matter fibers in the brain. We hypothesized that the maze tests in neuropsychological tests assessed reasoning and problem-solving abilities dependent on the integrity of brain white matter fibers, and assessed this relationship using diffusion tensor imaging (DTI) in depressed patients and healthy controls. METHODS: Participants aged from 18 to 50 years were recruited from Zhumadian Second People's Hospital from July 2018 to August 2019. The sample included 33 clinically diagnosed individuals with major depressive disorder (MDD) and 24 healthy volunteers (HVs). All subjects underwent Neuropsychological assessment battery (NAB) maze tests and DTI. Tract-based spatial statistics technology in FSL software was used to process DTI data, and threshold-free cluster enhancement (TFCE) was used to perform multiple comparison corrections. The fractional anisotropy (FA) of white matter fibers in the MDD group and HVs group were compared and extracted. Pearson correlation was used to analyze the relationship between FA and NAB scores and HAMD scores. RESULTS: The mean NAB maze test score for the MDD group was lower than the HVs group, and the difference was statistically significant (F = 11.265, p = .037). The FA value of the body of corpus callosum and cerebral peduncle right in the depression group was lower than that in the healthy control group, and the difference was statistically significant (p < .05). FA value of the body of corpus callosum was positively correlated with NAB score (r = 0.400, p = .036), but not with the HAMD score (r = 0.065, p = .723). CONCLUSIONS: The decreased ability of reasoning and problem-solving in MDD may be due to the decreased integrity of the white matter fibers of the body of the corpus callosum.

Identifying the difference in time perception between major depressive disorder and bipolar depression through a temporal bisection task.

BACKGROUND: It is difficult to make a precise diagnosis to distinguish patients with Major Depressive Disorder (MDD) from patients with Bipolar Depressive Disorder (current depressive episode, BD). This study will explore the difference in time perception between MDD and BD using a temporal bisection task. METHODS: In this temporal bisection task, 30 MDD patients, 30 BD patients, and 30 healthy controls (HC) had to categorize a signal duration, between 400 and 1600 milliseconds (ms), as either short or long. A repeated measurement analysis of variance with 3 (subject type) × 7 (time interval) was performed on the long response ratio with Bonferroni correction for multiple comparisons. Origin software was used to calculate the subjective bisection point (BP), difference limen (DL), and Weber ratio (WR). The Hamilton Depression Rating Scale for depression-17 was used to assess depressive symptoms in the patients. RESULTS: The data showed that the interaction effect between subject type and duration was significant (F (6,498) = 4.656, p <0.001, η2p = 0.101). At 400 ms, and the long response of the MDD group was greater than HC group (p<0.017, Bonferroni-corrected). At 1200, 1400 and 1600 ms, the long response of BD group is smaller than HC group, (p<0.017, Bonferroni-corrected). The one-way ANOVA revealed significant difference among the HC, MDD and BD groups in the BP values WR values, F(2, 81) = 3.462, p = 0.036 vs. F(2, 81) = 3.311, p = 0.042. Post-hoc tests showed that the value of BP in the MDD group was less than BD group (p = 0.027) and the value of BP in the MDD group was less than HC group (p = 0.027), while there was not significant difference of BP values between BD group and HC group. The WR values in MDD group larger than the HC group (p = 0.022). LIMITATIONS: Severity of depression not divided and analyzed according to the Hamilton Depression Rating Scale score. CONCLUSION: The time perception of the MDD and BD groups was different from that of the HC group, they overestimated short time periods. Compared with the BD group, the MDD group had a smaller time bisector, and these patients felt that time passed more slowly. The time sensitivity of MDD group and BD group were less than the HC group. However, there was no statistical difference in time sensitivity between the MDD and BD groups.

Facial Expression Recognition and ReHo Analysis in Major Depressive Disorder.

Objective: To explore the characteristics of expression recognition and spontaneous activity of the resting state brain in major depressive disorder (MDD) patients to find the neural basis of expression recognition and emotional processing. Methods: In this study, two of the six facial expressions (happiness, sadness, anger, fear, aversion, and surprise) were presented in quick succession using a short expression recognition test. The differences in facial expression recognition between MDD patients and healthy people were compared. Further, the differences in ReHo values between the two groups were compared using a resting-state functional magnetic resonance imaging (fMRI) scan to investigate the characteristics of spontaneous brain activity in the resting state and its relationship with clinical symptoms and the accuracy of facial expression recognition in patients with MDD. Results: (1) The accuracy of facial expression recognition in patients with MDD was lower than that of the HC group. There were differences in facial expression recognition between the two groups in sadness-anger (p = 0.026), surprise-aversion (p = 0.038), surprise-happiness (p = 0.014), surprise-sadness (p = 0.019), fear-happiness (p = 0.027), and fear-anger (p = 0.009). The reaction time for facial expression recognition in the patient group was significantly longer than that of the HC group. (2) Compared with the HC group, the ReHo values decreased in the left parahippocampal gyrus, left thalamus, right putamen, left putamen, and right angular gyrus, and increased in the left superior frontal gyrus, left middle temporal gyrus, left medial superior frontal gyrus, and right medial superior frontal gyrus in the patient group. (3) Spearman correlation analysis showed no statistical correlation between ReHo and HAMD-17 scores in MDD patients (p > 0.05). The ReHo value of the left putamen was negatively correlated with the recognition of fear-surprise (r = -0.429, p = 0.016), the ReHo value of the right angular gyrus was positively correlated with the recognition of sadness-anger (r = 0.367, p = 0.042), and the ReHo value of the right medial superior frontal gyrus was negatively correlated with the recognition of fear-anger (r = -0.377, p = 0.037). Conclusion: In view of the different performance of patients with MDD in facial expression tasks, facial expression recognition may have some suggestive effect on the diagnosis of depression and has clinical guiding significance. Many brain regions, including the frontal lobe, temporal lobe, striatum, hippocampus, and thalamus, in patients with MDD show extensive ReHo abnormalities in the resting state. These brain regions with abnormal spontaneous neural activity are important components of LCSPT and LTC circuits, and their dysfunctional functions cause disorder of emotion regulation. The changes in spontaneous activity in the left putamen, right angular gyrus, and right medial superior frontal gyrus may represent the abnormal pattern of spontaneous brain activity in the neural circuits related to emotion perception and may be the neural basis of facial expression recognition.

Metabolic and non-metabolic liver zonation is established non-synchronously and requires sinusoidal Wnts.

The distribution of complementary metabolic functions in hepatocytes along a portocentral axis is called liver zonation. Endothelial secreted Wnt ligands maintain metabolic zonation in the adult murine liver but whether those ligands are necessary to initiate zonation in the immature liver has been only partially explored. Also, numerous non-metabolic proteins display zonated expression in the adult liver but it is not entirely clear if their localization requires endothelial Wnts. Here we used a novel transgenic mouse model to compare the spatial distribution of zonated non-metabolic proteins with that of typical zonated metabolic enzymes during liver maturation and after acute injury induced by carbon tetrachloride (CCl4). We also investigated how preventing Wnt ligand secretion from endothelial cells affects zonation patterns under homeostasis and after acute injury. Our study demonstrates that metabolic and non-metabolic zonation are established non-synchronously during maturation and regeneration and require multiple endothelial Wnt sources.

Rapid isolation of highly pure single-stranded DNA from phagemids.

Single-stranded DNA (ssDNA) has many applications in molecular biology and biotechnology. The conventional method for the preparation of ssDNA from phagemids is laborious, costly, and inefficient. Here we describe an integrated protocol for consistent production of phagemid ssDNA from a bacteria/phagemid/help phage complex and rapid isolation and purification of the ssDNA with a silica column followed by duplex-specific nuclease digestion. The major advantages of our method are the expediency, low cost, and consistent yield of highly pure ssDNA that is suitable for direct sequencing and other applications. This method is especially useful for large-scale preparation of high-quality ssDNA.

Inhibition of connexin 43 hemichannels improves postoperative cognitive function in aged mice.

AIMS: Postoperative cognitive dysfunction (POCD) is a neurological disorder associated with neuroinflammation. Connexin 43 (Cx43), an essential component of gap junction, plays a crucial role in neuroinflammation. The present study was designed to investigate the role of Cx43 in the process of POCD. METHODS: POCD model was established in aged mice with internal fixation of tibial fractures. Cognitive function was examined using the Morris water maze test. Hippocampus was collected for reverse transcription polymerase chain reaction (RT-PCR), western blotting, and immunofluorescence assays. RESULTS: In the water maze test, mice undergoing surgery took longer time to reach target platform than the controls. IL-1ß and TNF-α mRNA expressions in the hippocampus were significantly increased in surgery mice. Cx43 protein presence in the hippocampus was increased in the surgery group. Treatment of Gap26, a specific blocker of Cx43 hemichannel, reduced the Cx43 protein presence, decreased mRNA expressions of IL-1ß and TNF-α, and improved cognitive score in the maze test. CONCLUSION: Internal fixation of tibial fractures in aged mice induces Cx43 hemichannels opening and enhances neuroinflammation in the hippocampus, leading to cognitive impairment. Administration of Gap26 reduces neuroinflammation in the hippocampus and improves postoperative cognitive function.

A survey on compliance with secondary stroke prevention guidelines and follow up for the inpatients with atherosclerotic cerebral infarction/transient ischemic attack.

OBJECTIVE: Poor compliance with evidence-based medicine guidelines could significantly influence the effect of stroke prevention strategies. The objective of this survey is to evaluate the current status of adherence to secondary prevention guidelines based on evidence-based medicine and related lifestyle modifications, both at hospital discharge and 90 days after discharge for inpatients with atherosclerotic cerebral infarction/transient ischemic attack (TIA) in Beijing. METHODS: The survey enrolled patients with cerebral infarction/TIA, from seven hospitals in Beijing consecutively from 1 October 2006 to 1 May 2007, and was designed to record detailed information including ACEI/ARB, statins, anti-platelet agent therapy, carotid endarterectomy, angioplasty or stent, smoking and weight control behaviors. RESULTS: Seven hundred and eight cerebral infarction/TIA inpatients had been enrolled over the past 7 months from the year of 2006 to 2007. The proportion of patients with ischemic stroke that have not taken any anti-platelet agents, statins and ACEI/ARB were 0.4, 41.8 and 63.6%, respectively. Twenty-seven percent of the total patients have not followed the instructions on quitting tobacco. Five hundred and eighty-eight patients who are suitable to have drug therapy were followed up 90 day after discharge: 26.9% have not adhered to anti-platelet agents; 52.6% have not been treated by statins, and 59.4% have not had ACEI/ARB to lower blood pressure. Only 66.9% of the smokers have been instructed by clinicians on smoking cessation at the time of discharge. CONCLUSION: The current status of drug therapy and life modification for secondary prevention on ischemic stroke and TIA in Beijing, China, is still very challenging. Clinicians should pay more attention to the patients' adherence to secondary stroke prevention guidelines, to enhance the effectiveness of stroke prevention through filling the gap between the clinical practice and evidence.

[A survey on cerebral infarction/transient ischemic attack inpatients compliance with secondary stroke prevention and follow-up 90 days].

OBJECTIVE: Poor compliance with evidence-based-medicine guidelines could significantly influence the effect of stroke prevention strategies. The objectives of this survey are to investigate the current status in Beijing of cerebral infarction/TIA (transient ischemic attack) inpatients' adherence to the evidence-based-medicine secondary prevention and behavior modifications both at the discharge and at 90-day follow up. METHODS: The survey included cerebral infarction/TIA patients successively admitted from 1, Oct 2006 to 1, May 2007, used ACEI/ARB, Statin, anti-platelet agents therapy, accepted carotid endarterctomy or angioplasty or stent, and modified behaviors to stop smoking and control weight. Data of patients during hospitalization were obtained from the medical documents in the inpatient department of 7 centers. The detailed information included the medicine therapy, lifestyle modifications, patients' social demographic background (age, sex, education and way of payment), major risk factors for stroke, and ischemic event subtypes (TIA or cerebral infarction). Above information of part of patients were collected through telephone interview at 90-day follow-up if the patients were not able to visit the clinic. RESULTS: 708 cerebral infarction/TIA inpatients who didn't have contraindications were included. Among them, the patents who haven't used anti-platelet agents, nor taken statin, nor accepted ACEI/ARB were about 0.4%, 41.8% and 63.6% respectively. Neither 27% of the patients have accepted the instructions on stop smoking. While about 588 patients suitable to drug therapy were followed up at 90 days, but the percentage of these patients who haven't compliance on anti-platelet agents, statin, ACEI/ARB was 26.9%, 52.6% and 59.4% respectively. Only 66.9% of the smoking patients have received the doctor instructions on smoking cessation. CONCLUSION: Stroke recurrence rate in China is higher than that of average figures in western countries. One of the key reasons of high recurrence of stroke in China is the poor adherence to stroke secondary prevention guidelines. Thus, investigate current status of secondary prevention among hospitals in capital of China and promote strategies to enhance the adherence to the guidelines and fill the gap between the clinical practice and evidence-based medicine in China, which is able to lower the stroke recurrence and save lives are urgently needed. Physician should take great care of the patient's compliances on the evidenced-based-medicine secondary prevents and behavior modifications, and take effective measures to improve the compliances.

A Pck1-directed glycogen metabolic program regulates formation and maintenance of memory CD8+ T cells.

CD8+ memory T (Tm) cells are fundamental for protective immunity against infections and cancers 1-5 . Metabolic activities are crucial in controlling memory T-cell homeostasis, but mechanisms linking metabolic signals to memory formation and survival remain elusive. Here we show that CD8+ Tm cells markedly upregulate cytosolic phosphoenolpyruvate carboxykinase (Pck1), the hub molecule regulating glycolysis, tricarboxylic acid cycle and gluconeogenesis, to increase glycogenesis via gluconeogenesis. The resultant glycogen is then channelled to glycogenolysis to generate glucose-6-phosphate and the subsequent pentose phosphate pathway (PPP) that generates abundant NADPH, ensuring high levels of reduced glutathione in Tm cells. Abrogation of Pck1-glycogen-PPP decreases GSH/GSSG ratios and increases levels of reactive oxygen species (ROS), leading to impairment of CD8+ Tm formation and maintenance. Importantly, this metabolic regulatory mechanism could be readily translated into more efficient T-cell immunotherapy in mouse tumour models.

A survey on adherence to secondary ischemic stroke prevention.

Reduced adherence and compliance to discharge instructions and protocols could significantly influence the ability of any stroke prevention strategy. The goals of this investigation were to evaluate the adherence to secondary prevention strategies within 1 year after ischemic stroke and to identify possible causes of poor compliance with these strategies. Patients who had suffered either acute ischemic stroke or transient ischemic attacks (TIA) were recruited retrospectively through telephone follow-up. The survey included whether the patient was prescribed antithrombotic treatment at discharge and reasons for non-compliance with this prescription both immediately after discharge and 1 year after discharge. Of 472 (73.8%) patients with detailed clinical data who were finally evaluated in this survey, 326 (69.1%) were still under antithrombotic treatment and 172 (36.4%) underwent the same antithrombotic agent as prescribed when discharged. We found that medical insurance and free medical care were able to promote compliance with medication in stroke patients for secondary prevention, while administration of non-aspirin antithrombotic agents or a poor ability for daily activities (Barthel index, BI) had significantly negative effects on medication compliance in stroke patients. Under the conditions of this observational study, adherence to stroke prevention strategies was poor. Income levels, categories of antithrombotic agents and the personal living ability are closely related to compliance. The results suggest that doctors should pay more attention to the secondary prevention of stroke. We suggest that providing stroke patients with detailed instructions for medication usage, physicians could increase the potential that their secondary prevention of stroke could be increased.