The mechanism of impaired delayed recall verbal memory function in Parkinson's disease with orthostatic hypotension: a multiple imaging study.

Introduction: Orthostatic hypotension (OH) frequently accompanies autonomic dysfunction and is an important risk factor for cognitive impairment in Parkinson's disease (PD). However, the association between different cognitive functions and OH in PD patients is not yet fully understood. Methods: This study aimed to evaluate the scores of different cognitive domains and multiple parameters using different imaging techniques on PD patients with or without OH. A total number of 31 PD patients with OH (n = 20) and without OH (n = 11) were recruited from the Department of Neurology, Beijing Xuanwu Hospital for this study. All patients underwent beat-to-beat non-invasive blood pressure recordings and an active standing test to evaluate neurogenic OH and a global neuropsychological test to assess cognitive function. All patients underwent dynamic cerebral autoregulation (dCA) measurement, brain magnetic resonance imaging (MRI), and brain 18fluorine-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). Results: The results showed that OH patients had poor delayed recall verbal memory when compared with the PD patients without OH (1.75 ± 1.59 vs. 3.10 ± 1.73, p = 0.042). The dCA test indicated a significant difference in the right very low-frequency (VLF) gain between two groups (1.27 ± 0.17 vs. 1.10 ± 0.26, p = 0.045) and the brain 18F-FDG PET/CT indicated a significant difference in the SUV (right medial temporal lobe) to SUV (occipital lobe) ratio (0.60 ± 0.08 vs. 0.67 ± 0.11, p = 0.049). Meanwhile, these two imaging parameters were negatively correlated (p < 0.001). Furthermore, the score of a delayed recall verbal memory in the OH group was positively correlated with the right medial temporal lobe to occipital lobe ratio (p < 0.001) and was negatively correlated with the right VLF gain (p = 0.023). Discussion: PD with OH patients had poor delayed recall memory, which might have been caused by the decreased metabolic dysfunction of specific medial temporal lobe due to the impaired dCA ability.

Highly Deformable High-Strength SiO2 Aerogel Designed with an Alternating Structure of Hard Cores and Flexible Chains for Thermal Insulation.

Thermally insulating aerogels can now be prepared from ceramics, polymers, carbon, and metals and composites between them. However, it is still a great challenge to make aerogels with high strength and excellent deformability. We propose a design concept of hard cores and flexible chains that alternately construct the aerogel skeleton structure. The approach gives the designed SiO2 aerogel excellent compressive (fracture strain 83.32%), tensile. and shear deformabilities, corresponding to maximum strengths of 22.15, 1.18, and 1.45 MPa, respectively. Also, the SiO2 aerogel can stably perform 100 load-unload cycles at a 70% large compression strain, demonstrating an excellent resilient compressibility. In addition, the low density of 0.226 g/cm3, the high porosity of 88.7%, and the average pore size of 45.36 nm effectively inhibit heat conduction and heat convection, giving the SiO2 aerogel outstanding thermal insulation properties [0.02845 W/(m·K) at 25 °C and 0.04895 W/(m·K) at 300 °C], and the large number of hydrophobic groups itself also gives it excellent hydrophobicity and hydrophobic stability (hydrophobic angle of 158.4° and saturated mass moisture absorption rate of about 0.327%). The successful practice of this concept has provided different insights into the preparation of high-strength aerogels with high deformability.

The microstructural abnormalities of cingulum was related to patients with mild cognitive impairment: a diffusion kurtosis imaging study.

OBJECTIVE: Our study aimed to investigate the correlations between microstructural changes of cingulum and patients with mild cognitive impairment (MCI) by diffusion kurtosis imaging (DKI) technique. METHOD: A total of 104 patients with cerebral small vessel diseases (cSVD) were retrospectively enrolled in this study. According to Montreal Cognitive Assessment Scale (MoCA) scores, these patients were divided into MCI group (n = 59) and non-MCI group (n = 45). The general clinical data was collected and analyzed. The regions of interests (ROIs) were selected for investigation in cingulum. The values of DKI parameters were measured in each ROI and compared between the two groups, the correlations between DKI parameters and MoCA scores were examined. RESULTS: Compared to non-MCI group, MCI patients had more severe white matter hyperintensities (WMHs) (P = 0.038) and lower MoCA scores (P < 0.01). MCI patients showed significantly decreased fractional anisotropy (FA), axial kurtosis (AK), mean kurtosis (MK), radial kurtosis (RK), and kurtosis fractional anisotropy (KFA) in the left cingulum in the cingulated cortex (CgC) region (all P < 0.0125). In the left CgC region, FA, AK, MK, RK, and KFA were positively correlated with MoCA scores (r = 0.348, 0.409, 0.310, 0.441, 0.422, all P < 0.001). Meanwhile, FA, AK, MK, RK, and KFA were also positively correlated with MoCA scores (r = 0.338, 0.352, 0.289, 0.380, 0.370, all P < 0.001) in the right CgC region. CONCLUSION: DKI technique could be used to explore the microstructural changes of cingulum in MCI patients and DKI-derived parameters might be feasible to evaluate MCI patients.

Natural variation in the plant polyadenylation complex.

Messenger RNA polyadenylation, the process wherein the primary RNA polymerase II transcript is cleaved and a poly(A) tract added, is a key step in the expression of genes in plants. Moreover, it is a point at which gene expression may be regulated by determining the functionality of the mature mRNA. Polyadenylation is mediated by a complex (the polyadenylation complex, or PAC) that consists of between 15 and 20 subunits. While the general functioning of these subunits may be inferred by extending paradigms established in well-developed eukaryotic models, much remains to be learned about the roles of individual subunits in the regulation of polyadenylation in plants. To gain further insight into this, we conducted a survey of variability in the plant PAC. For this, we drew upon a database of naturally-occurring variation in numerous geographic isolates of Arabidopsis thaliana. For a subset of genes encoding PAC subunits, the patterns of variability included the occurrence of premature stop codons in some Arabidopsis accessions. These and other observations lead us to conclude that some genes purported to encode PAC subunits in Arabidopsis are actually pseudogenes, and that others may encode proteins with dispensable functions in the plant. Many subunits of the PAC showed patterns of variability that were consistent with their roles as essential proteins in the cell. Several other PAC subunits exhibit patterns of variability consistent with selection for new or altered function. We propose that these latter subunits participate in regulatory interactions important for differential usage of poly(A) sites.

COVID-19 pandemic impacts on the elderly: the relationship between PPPD and prefrontal alpha rhythm.

BACKGROUND: In the COVID-19 epidemic more patients presented with persistent postural-perceptual dizziness (PPPD), but it has received little attention by the doctors in China and many patients reject psychological measurements or scales. Therefore, there is an urgent need for an objective method to diagnose and evaluate PPPD. OBJECTIVE: To investigate the effect of the COVID-19 epidemic on elderly PPPD patients and define the relationship between prefrontal alpha rhythm asymmetry (FAA) by Electroencephalography (EEG) and PPPD. METHODS: This case-control study was conducted to discuss the differences of elderly outpatients (>60 years) with PPPD during the peak period of COVID-19 in 2020 and the corresponding period in 2019, and collect the prefrontal FAA value in PPPD during COVID-19 outbreak, which were compared to its FAA in healthy control. RESULTS: Compared with the same period in 2019, the number of elderly PPPD patients during the epidemic period in 2020 increased significantly (16.4%, p = 0.000, x2 =31.802) . The left alpha wave signal power (F3) was significantly higher than the right alpha wave signal power (F4) (Z= -3.073, p = 0.002). In PPPD patients FAA were significantly lower in patients compared to control group (Z = -11.535, p = 0.000). There was a negative correlation between FAA and HAMA scores (R2 =0.906, p < 0.05) and a negative correlation between FAA and HAMD scores (R2 =0.859, p < 0.05), too. CONCLUSIONS: The increase in cases of elderly PPPD patients is most likely attributed to the mental health in older adults during the COVID-19 pandemic. Less left frontal brain activity in EEG may be related to elderly PPPD.

Research on Quantitative Model of Brand Recognition Based on Sentiment Analysis of Big Data.

This paper takes laptops as an example to carry out research on quantitative model of brand recognition based on sentiment analysis of big data. The basic idea is to use web crawler technology to obtain the most authentic and direct information of different laptop brands from first-line consumers from public spaces such as buyer reviews of major e-commerce platforms, including review time, text reviews, satisfaction ratings and relevant user information, etc., and then analyzes consumers' sentimental tendencies and recognition status of the product brands. This study extracted a total of 437,815 user reviews of laptops from e-commerce platforms from January 1, 2019 to December 31, 2021, and performed data preprocessing on the obtained review data, followed by sentiment dictionary construction, attribute expansion, text quantification and algorithm evaluation. This paper analyzed the information receiving and processing hierarchy of the quantitative model of brand recognition, discussed the interactive relationship between brand recognition and consumer sentiment, discussed the brand recognition bias, style and demand in the context of big data, and performed the sentiment statistics and dimension analysis in the quantitative model of brand recognition. The study results show that the quantitative model of brand recognition based on sentiment analysis of big data can transform and map the keywords in text to word vectors in the high-dimensional semantic space by performing unsupervised machine learning on the text based on artificial neural network computer bionic metaphors; the model can accumulate each brand-related buyer review in the corresponding brand recognition dimension, so as to obtain the value of each product in each dimension of brand recognition; finally, the model will add the values of each dimension of brand recognition, that is, obtain the relevant value of the sum of each brand recognition. The results of this paper may provide a reference for further research on the quantitative model of brand recognition based on sentiment analysis of big data.

Genome-wide identification and characterization of aquaporins in mangrove plant Kandelia obovata and its role in response to the intertidal environment.

Aquaporins (AQPs) play important roles in plant growth, development and tolerance to environmental stresses. To understand the role of AQPs in the mangrove plant Kandelia obovata, which has the ability to acquire water from seawater, we identified 34 AQPs in the K. obovata genome and analysed their structural features. Phylogenetic analysis revealed that KoAQPs are homologous to AQPs of Populus and Arabidopsis, which are evolutionarily conserved. The key amino acid residues were used to assess water-transport ability. Analysis of cis-acting elements in the promoters indicated that KoAQPs may be stress- and hormone-responsive. Subcellular localization of KoAQPs in yeast showed most KoAQPs function in the membrane system. That transgenic yeast with increased cell volume showed that some KoAQPs have significant water-transport activity, and the substrate sensitivity assay indicates that some KoAQPs can transport H2 O2 . The transcriptome data were used to analyze the expression patterns of KoAQPs in different tissues and developing fruits of K. obovata. In addition, real-time quantitative PCR analyses combined transcriptome data showed that KoAQPs have complex responses to environmental factors, including salinity, flooding and cold. Collectively, the transport of water and solutes by KoAQPs contributed to the adaptation of K. obovata to the coastal intertidal environment.

A Wearable Gait Analysis System Used in Type 2 Diabetes Mellitus Patients: A Case-Control Study.

BACKGROUND: Previous studies have shown that the gait of patients with type-2 diabetes mellitus is abnormal compared with the healthy group. Currently, a three-dimensional motion analyzer system is commonly used for gait analysis. However, it is challenging to collect data and use in clinical study due to extensive experimental conditions and high price. In this study, we used a wearable gait analysis system (Gaitboter) to investigate the spatial and temporal parameters, and kinematic data of gait in diabetic patients, especially those with peripheral neuropathy. The aim of the study is to evaluate the wearable gait analysis system in diabetic study. MATERIALS AND METHODS: We conducted a case-control study to analyze the gait of type 2 diabetes mellitus. Gaitboter was used to detect and collect gait data in the ward of Beijing Chao-yang Hospital, Capital Medical University from June 2018 to October 2018. We collected the gait data of participants (N= 146; 73 patients with type 2 diabetes, 16 with peripheral neuropathy and 57 without peripheral neuropathy, and 73 matched controls). The gait data (stance phase, swing phase, double-foot stance phase, single-foot stance phase, walking cadence, stride length, walking speed, off-ground angle, landing angle, maximum swing angle, minimum swing angle, and foot progression angle) in diabetic patients were recorded and compared with controls. SPSS 22.0 statistical software was used to analyzed the gait parameter data. RESULTS: We found that the landing angle and the maximum swing angle of diabetes patients with or without peripheral neuropathy were significantly less than those of the control group (P < 0.05). The walking speed of diabetes patients with peripheral neuropathy is significantly less than those of the control group (P < 0.05). CONCLUSION: This study confirms that the wearable gait analysis system (Gaitboter) is an ideal system to identify abnormal gait in patients with type 2 diabetes and provides a new device and method for diabetes-related gait research.

The Impact of Coronavirus Disease 2019 Epidemic on Dizziness/Vertigo Outpatients in a Neurological Clinic in China.

Objective: This study aims to investigate the impact of the coronavirus disease 2019 (COVID-19) epidemic on dizziness/vertigo outpatients in a neurological clinic in China. Methods: Against the background of the COVID-19 epidemic, the data of patients who visited the neurological clinic of Beijing Chaoyang Hospital West Branch during the pandemic (February 1-May 30, 2020) and the corresponding period in 2019 (February 1-May 30, 2019) were analyzed, and patients with dizziness/vertigo from these two periods were compared to discover their demographic features and etiologic distribution according to their age and sex. Result: The absolute number of neurological outpatients decreased from 14,670 in 2019 to 8,763 in 2020 (-40.3%), with a corresponding decline in dizziness/vertigo patients (2019: n = 856; 2020: n = 1,436, -40.4%). Dizziness/vertigo was more common in women than men in these two periods (2019: women = 63.6%; 2020: women = 63.1%, p = 0.82). The overall etiology distribution was different among all disorders between the two periods (p < 0.001). There was an increase in benign paroxysmal positional vertigo (BPPV) (2019 vs. 2020: 30.7 vs. 35%, p < 0.05) and psychogenic/persistent postural perceptual dizziness (PPPD) (2019 vs. 2020: 28.5 vs. 34.6%, p < 0.05) while a decrease in vascular vertigo during the epidemic (2019 vs. 2020: 13 vs. 9.6%, p < 0.05). During the epidemic, the top three causes of dizziness/vertigo were BPPV (35%), psychogenic/PPPD (34.6%), and vascular vertigo (9.6%). A female predominance was observed in BPPV (women = 67.7%, p < 0.05) and psychogenic/PPPD (women = 67.6%, p < 0.05). In addition, the etiology ratio of different age groups was significantly different (p < 0.001). The most common cause for young and young-old patients was BPPV, and the most common cause for middle-aged and old-old patients was psychogenic/PPPD. Conclusion: The absolute number of outpatients with dizziness/vertigo during the COVID-19 pandemic was reduced during the early period of the COVID-19 outbreak. BPPV and psychogenic/PPPD were more abundant, and vascular vertigo was less frequent. Based on those data, health-care management policy for dizziness/vertigo and mental disorder should be developed during the outbreak of COVID-19 and other infective diseases.

Anti-IL-23 exerted protective effects on cerebral ischemia-reperfusion injury through JAK2/STAT3 signaling pathway.

Ischemia-reperfusion frequently occurs in ischemic cerebral vascular disease, during which the inflammatory signaling plays essential roles. The aim of this study was to discover the efficacy of the antibody to a key immune cytokine IL-23 (anti-IL-23) for the therapy of cerebral ischemia-reperfusion injury. We established the cerebral ischemia-reperfusion injury model by middle cerebral artery occlusion (MCAO). Anti-IL-23 injection attenuated lesions indicated by histology study. RT-PCR and Western blot were employed to detect the mRNA and protein expression of JAK2 and STAT3 after anti-IL-23 treatment. ELISA was utilized to measure the levels of MDA (malondialdehyde) and superoxide dismutase (SOD). Moreover, curcumin and IL-6 were implicated in the endogenous intervention of IL-23 signaling in vivo. Our data demonstrated that the treatment of anti-IL-23 might transcriptionally activate the classic immune pathway in the brain. Anti-IL-23 augmented phosphorylation levels of both JAK2 and STAT3, suggesting the amplification signaling of JAK/STAT after exogenous IL-23 intervention. Anti-IL-23 reduced ROS molecules of STAT downstream in the serum and brain. It also alleviated the injury by bringing down levels of MDA and SOD in the serum. JAK2 inhibitor could abolish the effect of anti-IL-23 whereas JAK3 ameliorated the injury. The combination of anti-IL-23 and JAK3i could reduce infarct volume more effectively. In summary, this study indicated that anti-IL-23 had protective effects against cerebral ischemia-reperfusion injury by targeting the immune specific JAK2-STAT3 in JAK/STAT pathway.

Microstructural changes in the cingulate gyrus of patients with mild cognitive impairment induced by cerebral small vessel disease.

Objective: The purpose of our study was to distinguish the changes in the microstructure of the cingulate cortex in patients with mild cognitive impairment (MCI) induced by cerebral small vessel disease (CSVD).Method: 80 patients were diagnosed with CSVD in this study, including 55 patients with MCI and 25 patients without MCI. Diffusion kurtosis imaging (DKI) and Montreal cognitive assessment (MoCA) were performed in all patients. The anterior cingulate gyrus, posterior cingulate gyrus and middle cingulate gyrus were selected as the regions of interest, and some parameters were recorded.Results: Compared with the non-MCI group, the MCI group mainly showed obviously higher mean diffusion (MD) and radial diffusion (RD) values (P = 0.022 and P = 0.029) but lower fractional anisotropy (FA), axial kurtosis (AK), mean kurtosis (MK) and radial kurtosis (RK) values (P = 0.047, P = 0.001, P < 0.01, and P = 0.001, respectively) in the right anterior cingulate gyrus. Meanwhile, in the right posterior cingulate gyrus, the MCI group also showed higher axial diffusion (AD) and MD (P = 0.027 and P = 0.030) and lower AK (P = 0.014). Additionally, negative correlations of AD, MD, and RD with MoCA scores and positive correlations of FA, AK, MK and RK with MoCA scores were observed in some regions of the cingulate gyrus.Conclusions: DKI is a good method to examine microstructural damage in the cingulate cortex, and some parameters of DKI may be used as imaging biomarkers to detect early MCI in patients with CSVD.

Association with CYP2C19 polymorphisms and Clopidogrel in treatment of elderly stroke patients.

BACKGROUND: Clopidogrel is an antiplatelet drug used in the treatment of ischemic stroke. Safety and efficacy of clopidogrel has been confirmed in CAPRIE, PRoFESS trials. However, these studies focused on patients aged less than 75 years. CYP2C19 polymorphisms resulted in individual differences in clopidogrel response. Our objective was to determine whether elderly stroke patients aged over 75 years would benefit from CYP2C19-genotype-guided strategy for the secondary prevention of stroke. METHODS: A retrospective analysis of patients aged 75 years or older with non-cardiogenic stroke who received 75 mg clopidogrel was performed. CYP2C19 genotype-guided group included noncarriers of CYP2C19*2 or CYP2C19*3 loss-of-function alleles (LoFA) and compared against the non-genotype-guided group which may carriers CYP2C19 LoFA or not. The primary endpoints were composite of stroke and myocardial infarction at 24 months' follow-up. RESULTS: Two hundred one patients were included: 99 in the genotype-guided group and 102 in the non-genotype-guided group. Kaplan-Meier(KM)analysis showed that CYP2C19 gene polymorphism was associated with the rate of the primary endpoints (P = 0.0031). The primary endpoints occurred in 13 patients (13.1%) in the genotype-guided group and in 30 patients (29.4%) in the non-genotype-guided group (hazard ratio(HR), 0.39; 95% confidence interval(CI), 0.20 to 0.75; p = 0.004). Cox regression analysis showed that CYP2C19 genotype-guided strategy was a protective factor for the primary endpoints (HR, 0.39; 95% CI:0.20 to 0.74, P = 0.004). CONCLUSION: The CYP2C19 genotype-guided strategy could reduce the occurrence of composite of stroke and myocardial infarction compared to a non-genotype-guided strategy for non-cardiogenic stroke patients aged 75 years or older who received clopidogrel.

Two cases of rt-PA with dual antiplatelet therapies with capsular warning syndrome.

RATIONALE: Capsular warning syndrome (CWS) is a term to describe stereotyped lacunar transient ischemic attacks (TIAs). Patients with CWS are at high risk of developing completed stroke. However, the exact pathophysiology of CWS is still unclear, and there is no conclusive clinical strategy for CWS patients. PATIENT SYMPTOMS: Two cases of middle-aged men with hypertension, hyperlipidemia, and diabetes mellitus presented with fluctuating right-sided weakness, numbness, and dysarthria. DIAGNOSES: These two patients were diagnosed with CWS. INTERVENTIONS: Recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis (0.9 mg/kg) was administered first and treated with aspirin (100 mg) and clopidogrel (75 mg) after 24 h of rt-PA for 21 days following by aspirin (100 mg) alone. OUTCOMES: Both cases got favorable clinical outcomes of somatic symptoms. In addition, diffusion-weighted imaging (DWI or DW-MRI) showed that ischemic injury disappeared in case 1 while maintained within a reasonable range in case 2. LESSONS: Early recognition and rt-PA/dual antiplatelet treatment may be an effective strategy for patients with CWS.

Low-dose antiplatelet therapy survey after intracerebral hemorrhage in China: a retrospective hospital-based study.

Restarting of antiplatelet therapy (AT) for patients with a history of intracerebral hemorrhage (ICH) is still a clinical dilemma in China. We aimed to investigate the association between low-dose AT and the long-term clinical outcome in Chinese ICH patients. A total of 312 patients with a history of ICH were retrospectively enrolled and followed. The ischemic vascular events, recurrent ICH, and all-cause death were reviewed retrospectively. We explored the predictors of ischemic vascular events and recurrent ICH from all patients using Cox proportional hazard regression model. One hundred fifty-one (48.4%) patients were treated with low-dose AT, and the median duration of follow-up was 4.0 years (interquartile range, 2.5-5 years). Compared to 30 (19.8%) of 151 participants who restarted low-dose AT had ischemic vascular events, 51 (31.7%) of 161 participants who did not receive AT showed ischemic vascular events (p=0.025). Eighteen (11.9%) of 151 participants treated with low-dose AT had recurrent ICH and 21 (13.0%) of 161 in non-AT participants (p=0.830). Cox regression analysis also showed that diabetes mellitus was an independent risk factor for ischemic vascular events (p=0.029). Uncontrolled blood pressure (BP) was independently associated with the risk for both ischemic vascular events (p=0.025) and recurrent ICH (p=0.001). Atrial fibrillation (AF) was an independent risk factor for recurrent ICH among patients with a history of ICH (p=0.018). In a Chinese population of patients with predominantly deep, mild to moderate severity ICH, restarting of low-dose AT at a median of 6.2 months was associated with a lower risk of ischemic vascular events without increased risk of recurrent ICH.

AG490 protects cerebral ischemia/reperfusion injury via inhibiting the JAK2/3 signaling pathway.

BACKGROUND: Cerebral ischemia/reperfusion injury is a severe problem in patients with brain ischemia. Brain injury caused by the immune response is important in the pathogenesis of cerebral ischemia/reperfusion injury and immune pathways. It is important to investigate potential targets for the treatment of cerebral ischemia/reperfusion injury. METHODS: In this experiment, we evaluated the effect of an exogenous JAK antagonist AG490 in the cerebral ischemia/reperfusion injury model, which was established by middle cerebral artery occlusion (MCAO). Histology study, TUNEL staining, Western blot, and RT-PCR were employed to examine the effects of AG490 in cerebral ischemia/reperfusion injury. RESULTS: In the brain tissue of MCAO mice, JAK2 was highly expressed. AG490 is an inhibitor of JAK2, which reduced the phosphorylation level of JAK2. AG490 downregulated the phosphorylated activation of JAK3 and their downstream STAT3. The antiapoptotic activity of AG490 on cerebral ischemia/reperfusion injury mice was consistent with in vitro data. It reduced the phosphorylation of JAK2/JAK3/STAT3 and the apoptosis rate in cultured neurons upon apoptosis induction. Besides, we also observed the neuroprotective effects of AG490 on cerebral ischemia/reperfusion injury. Administration of AG490 could further enhance the expression of neurotrophins including BNDF, NT3, and the neurotrophin receptor TrkB. CONCLUSION: Therefore, AG490 is pluripotent for cerebral ischemia/reperfusion injury through both antiapoptosis and neuroprotective activities. The antiapoptosis effect is dependent on its regulation of the JAK-STAT pathway.

DNA Compatible Intermolecular Wittig Olefination for the Construction of α, ß-Unsaturated Carbonyl Compounds.

A robust DNA-compatible Wittig reaction mediated by PPh2CH3 has been validated for DNA-conjugated α-chloroacetamides with aldehydes and, alternatively, DNA-conjugated aldehydes with α-halo acetamides or ketones. Further, 2-aminopyridines were acylated with α-chloroacetyl chloride and then reacted with DNA-conjugated aldehydes. Lastly, a pilot library employing our optimized Wittig reaction protocol was synthesized. The ability to generate α,ß-unsaturated carbonyl compounds may be particularly useful for the design of DNA-encoded libraries capable of covalently interacting with protein targets.

Efficacy of cattle encephalon glycoside and ignotin in patients with acute cerebral infarction: a randomized, double-blind, parallel-group, placebo-controlled study.

Cattle encephalon glycoside and ignotin (CEGI) injection is a compound preparation formed by a combination of muscle extract from healthy rabbits and brain gangliosides from cattle, and it is generally used as a neuroprotectant in the treatment of central and peripheral nerve injuries. However, there is still a need for high-level clinical evidence from large samples to support the use of CEGI. We therefore carried out a prospective, multicenter, randomized, double-blind, parallel-group, placebo-controlled study in which we recruited 319 patients with acute cerebral infarction from 16 centers in China from October 2013 to May 2016. The patients were randomized at a 3:1 ratio into CEGI (n = 239; 155 male, 84 female; 61.2 ± 9.2 years old) and placebo (n = 80; 46 male, 34 female; 63.2 ± 8.28 years old) groups. All patients were given standard care once daily for 14 days, including a 200 mg aspirin enteric-coated tablet and 20 mg atorvastatin calcium, both taken orally, and intravenous infusion of 250-500 mL 0.9% sodium chloride containing 40 mg sodium tanshinone IIA sulfonate. Based on conventional treatment, patients in the CEGI and placebo groups were given 12 mL CEGI or 12 mL sterile water, respectively, in an intravenous drip of 250 mL 0.9% sodium chloride (2 mL/min) once daily for 14 days. According to baseline National Institutes of Health Stroke Scale scores, patients in the two groups were divided into mild and moderate subgroups. Based on the modified Rankin Scale results, the rate of patients with good outcomes in the CEGI group was higher than that in the placebo group, and the rate of disability in the CEGI group was lower than that in the placebo group on day 90 after treatment. In the CEGI group, neurological deficits were decreased on days 14 and 90 after treatment, as measured by the National Institutes of Health Stroke Scale and the Barthel Index. Subgroup analysis revealed that CEGI led to more significant improvements in moderate stroke patients. No drug-related adverse events occurred in the CEGI or placebo groups. In conclusion, CEGI may be a safe and effective treatment for acute cerebral infarction patients, especially for moderate stroke patients. This study was approved by the Ethical Committee of Peking University Third Hospital, China (approval No. 2013-068-2) on May 20, 2013, and registered in the Chinese Clinical Trial Registry (registration No. ChiCTR1800017937).

Effects of PP2A/Nrf2 on experimental diabetes mellitus-related cardiomyopathy by regulation of autophagy and apoptosis through ROS dependent pathway.

Diabetes mellitus-related cardiomyopathy (DMCMP) has been defined as ventricular dysfunction that occurs in diabetic patients independent of a recognized cause such as coronary artery disease or hypertension. Mechanisms underlying DMCMP have not been fully elucidated. In this study, the roles of protein phosphatase 2A/nuclear factor NF-E2-related factor 2 (PP2A/Nrf2) in experimental DMCMP induced by high glucose were studied in vitro and in vivo. The results showed that high glucose could induce experimental DMCMP and increase ROS generation, increase the expression and nuclear translocation of Nrf2, down-regulate the expression of PI3K/Akt/mTOR and up-regulate the expression of ERK, and activate the autophagy of cardiomyocytes. The activity or expression of PP2A in DMCMP increased. PP2A could up-regulate the expression of Nrf2 and promote cardiomyocytes autophagy and apoptosis. Inhibition of PP2A could reduce the expression of Nrf2 and inhibit the autophagy and apoptosis of cardiomyocytes. The results suggested that hyperglycemic-induced experimental DMCMP may be related to up-regulating the expression of Nrf2 through PP2A/Nrf2 pathway. These results will be helpful to elucidate the pathogenesis and mechanism of DMCMP and find targets for the development of new drugs to prevent or treat DMCMP.

Low-dose rt-PA may not decrease the incidence of symptomatic intracranial haemorrhage in patients with high risk of symptomatic intracranial haemorrhage.

BACKGROUND: Recombinant tissue plasminogen activator (rt-PA) has been used as the standard treatment for acute ischemic stroke (AIS). The following study investigates whether low-dose rt-PA can decrease the incidence of symptomatic intracranial haemorrhage (sICH) in AIS patients with high-risk sICH compared to standard-dose rt-PA. MATERIALS AND METHODS: Data from the Thrombolysis Implementation and Monitor of Acute Ischemic Stroke in China (TIMS-China) studies were assessed to explore risk factors for sICH after intravenous thrombolysis. For high-risk sICH patients (age ≧70 years old, or with diabetes, or serum glucose on admission >9.0 mmol/L, or NIHSS on admission>20, or with cardioembolism), standard-dose rt-PA (0.85 to 0.95 mg/kg) and low- dose rt-PA (0.5 to 0.7 mg/kg) were compared. Primary outcome measure was the incidence of sICH, and the secondary outcome measures were 7-day mortality and 90-day functional independence outcome (modified Rankin scale, 0-2). RESULTS: A total of 554 patients were enrolled (60 cases for low dose, and 494 cases for standard dose). Median rt-PA doses were 0.63 and 0.90 mg, respectively. After adjustment for the baseline variables, low-dose rt-PA did not decrease the incidence of sICH (per SITS-MOST criteria, 3.33% versus 2.23%, P = 0.3467) compared to low dose. The low-dose group revealed less functional independence outcomes (modified Rankin scale, 0-2) compared to standard-dose group (36.67% versus 52.43%; odds ratio = 0.49; p = 0.0204) at 90 days. CONCLUSIONS: Our study suggests that low-dose intravenous rt-PA for high-risk sICH stroke in Chinese patients may not decrease the incidence of sICH, and concomitant with a poor outcome compared to standard-dose rt-PA. ABBREVIATIONS: rt-PA: recombinant tissue plasminogen activator; AIS: acute ischemic stroke; sICH: symptomatic intracranial haemorrhage.