No abstract

Alzheimer’s disease (AD) is characterized pathologically by the deposition of β-amyloid peptides (Aβ) and the accumulation of neurofibrillary tangles (NFTs) composed of hyper-phosphorylated tau. Regardless of the pathological hallmarks, synaptic dysfunction is widely accepted as a causal event in AD. Of the two major types of synapses in the central nervous system (CNS): glutamatergic and GABAergic, which provide excitatory and inhibitory outputs respectively, abundant data implicate an impaired glutamatergic system during disease progression. However, emerging evidence supports the notion that disrupted default neuronal network underlies impaired memory, and that alterations of GABAergic circuits, either plays a primary role or as a compensatory response to excitotoxicity, may also contribute to AD by disrupting the overall network function. The goal of this review is to provide an overview of the involvement of Aβ, tau and apolipoprotein E4 (apoE4), the major genetic risk factor in late-onset AD (LOAD), in GABAergic neurotransmission and the potential of modulating the GABAergic function as AD therapy.

Intramolecular noncovalent interactions (INIs) have served as ap owerfuls trategy for accessing organic semiconductors with enhanced charge transport properties.Herein, we apply the INI strategy for developing dopant-free holetransporting materials (HTMs) by constructing two smallmolecular HTMs featuring an INI-integrated backbone for high-performance perovskite solar cells (PVSCs). Upon incorporating noncovalent S•••O interaction into their simplestructured backbones,t he resulting HTMs,B TORA and BTORCNA, showed self-planarized backbones,t uned energy levels,enhanced thermal properties,appropriate film morphology,a nd effective defect passivation. More importantly,t he high film crystallinity enables the materials with substantial hole mobilities,t hus rendering them as promising dopant-free HTMs.C onsequently,t he BTORCNA-based inverted PVSCs delivered ap ower conversion efficiency of 21.10 %w ith encouraging long-term device stability,o utperforming the devices based on BTRA without S•••O interaction (18.40 %). This work offers ap ractical approach to designing charge transporting layers with high intrinsic mobilities for highperformance PVSCs.

RAB39B is located on the X chromosome and encodes the RAB39B protein that belongs to the RAB family. Mutations in RAB39B are known to be associated with X-linked intellectual disability (XLID), Parkinson’s disease, and autism. However, the patho/physiological functions of RAB39B remain largely unknown. In the present study, we established Rab39b knockout (KO) mice, which exhibited overall normal birth rate and morphologies as wild type mice. However, Rab39b deficiency led to reduced anxiety and impaired learning and memory in 2 months old mice. Deletion of Rab39b resulted in impairments of synaptic structures and functions, with reductions in NMDA receptors in the postsynaptic density (PSD). RAB39B deficiency also compromised autophagic flux at basal level, which could be overridden by rapamycin-induced autophagy activation. Further, treatment with rapamycin partially rescued impaired memory and synaptic plasticity in Rab39b KO mice, without affecting the PSD distribution of NMDA receptors. Together, these results suggest that RAB39B plays an important role in regulating both autophagy and synapse formation, and that targeting autophagy may have potential for treating XLID caused by RAB39B loss-of-function mutations.

Intravenous thrombolysis (IVT) with recombinant tissue plasminogen activator (rt-PA) can improve clinical outcome in eligible patients with acute ischemic stroke (AIS). However, its efficacy is strongly time-dependent. This study was aimed to examine whether prehospital notification by emergency medical service (EMS) providers could reduce onset to needle time (ONT) and improve neurological outcome in AIS patients who received IVT. We prospectively collected the consecutive clinical and time data of AIS patients who received IVT during one year after the initiation of prehospital notification procedure (PNP). Patients were divided into three groups, including patients that transferred by EMS with and without PNP and other means of transportation (non-EMS). We then compared the effect of EMS with PNP and EMS use only on ONT, and the subsequent neurological outcome. Good outcome was defined as modified Rankin Scale score of 0-2 at 3-months. In 182 patients included in this study, 77 (42.3%) patients were transferred by EMS, of whom 41 (53.2%) patients entered PNP. Compared with non-EMS group, EMS without PNP group greatly shortened the onset to door time (ODT), but EMS with PNP group showed both a significantly shorter DNT (41.3 ± 10.7 min vs 51.9±23.8 min, t=2.583, p=0.012) and ODT (133.2 ± 90.2 min vs 174.8 ± 105.1 min, t=2.228, p=0.027) than non-EMS group. Multivariate analysis showed that the use of EMS with PNP (OR=2.613, p=0.036), but not EMS (OR=1.865, p=0.103), was independently associated with good outcome after adjusting for age and baseline NIHSS score. When adding ONT into the regression model, ONT (OR=0.994, p=0.001), but not EMS with PNP (OR=1.785, p=0.236), was independently associated with good outcome. EMS with PNP, rather than EMS only, improved stroke outcome by shortening ONT. PNP could be a feasible strategy for better stroke care in Chinese urban area.

By invoking intrachain noncovalent interactions (NCIs) in diazine-based mA-wA polymers, high and balanced hole and electron mobilities were achieved.

The development of high-performance n-type polymer semiconductors is powered by the design and synthesis of electron-deficient building blocks with optimized physicochemical properties. By meticulously installing an imide group onto fluorene and its cyanated derivative, we report here two very electron-deficient building blocks, imide-functionalized fluorenone (FOI) and its cyanated derivative (FCNI), both featuring a deep-lying lowest unoccupied molecular orbital energy level down to À 4.05 eV and highly coplanar framework, endowing them ideal units for constructing n-type polymers. Thus, a series of polymers are built from them, exhibiting unipolar n-type transport character with a highest electron mobility of 0.11 cm 2 V À 1 s À 1 . Hence, FOI and FCNI offer a remarkable platform for accessing high-performance n-type polymers and the imide functionalization of appropriate (hetero)arenes is a powerful strategy for developing polymers with deeplying LUMOs for n-type organic electronics.

To develop a quantitative assessment of collateral perfusion at CT and to investigate its value in the prediction of outcome in patients with acute ischemic stroke (AIS). Materials and Methods:This retrospective study reviewed data from consecutive patients with AIS and an occluded M1 segment of the middle cerebral artery who underwent pretreatment perfusion CT between May 2009 and August 2017. The maximum cerebral blood flow (CBF) of collateral vessels (cCBF max ) within the Sylvian fissure was calculated for each patient. Good outcome was defined as a 90-day modified Rankin scale score of 0-2. Multivariable logistic regression analysis was used to determine the relationship between cCBF max and (a) hemorrhagic transformation and (b) clinical outcome. Results:The final analysis included 204 patients (median age, 73 years; interquartile range, 62-80 years; 82 [40.2%] women). Multivariable logistic regression analysis showed that higher cCBF max was an independent predictor for (a) a lower risk of hemorrhagic transformation (odds ratio [OR], 0.99; 95% confidence interval [CI]: 0.98, 1.00; P = .009) after adjusting for baseline National Institutes of Health Stroke Scale (NIHSS), endovascular thrombectomy, baseline infarct core volume, and recanalization and (b) better outcome (OR, 1.02; 95% CI: 1.01, 1.03; P = .001) after adjusting for age, baseline NIHSS score, endovascular thrombectomy, hypertension, baseline infarct core volume, and recanalization, respectively. Conclusion:The measurement of maximum cerebral blood flow of collateral vessels within the Sylvian fissure is a feasible quantitative collateral assessment at perfusion CT. Maximum cerebral blood flow of collateral vessels was associated with clinical outcome in patients with acute ischemic stroke.