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Recent studies have shown that in the preclinical phase of Alzheimer's disease (AD), subtle cognitive changes can be detected using sensitive neuropsychological measures, and have proposed the concept of objectively-defined subtle cognitive decline (Obj-SCD). We aimed to assess the functional alteration of hippocampal subfields in individuals with Obj-SCD and its association with cognition and pathological biomarkers. Forty-two participants with cognitively normal (CN), 29 with Obj-SCD, and 55 with mild cognitive impairment (MCI) were retrospectively collected from the ADNI database. Neuropsychological performance, functional MRI, and cerebrospinal fluid (CSF) data were obtained. We calculated the seed-based functional connectivity (FC) of hippocampal subfields (cornu ammonis1 [CA1], CA2/3/dentate gyrus [DG], and subiculum) with whole-brain voxels. Additionally, we analyzed the correlation between FC values of significantly altered regions and neuropsychological performance and CSF biomarkers. The Obj-SCD group showed lower FC between left CA1-CA2/3/DG and right thalamus and higher FC between right subiculum and right superior parietal gyrus (SPG) compared with the CN and MCI groups. In the Obj-SCD group, FC values between left CA2/3/DG and right thalamus were positively associated with Auditory Verbal Learning Test (AVLT) recognition (r = 0.395, p = 0.046) and CSF Aβ

Background Smoking is a modifiable risk factor for Alzheimer's disease (AD). The insula plays a key role in both smoking and cognition. However, the smoking effects on insula-related networks in cognitively normal controls (CN) and mild cognitive impairment (MCI) patients remain unknown. Methods We recruited 129 CN (85 non-smokers and 44 smokers) and 83 MCI (54 non-smokers and 29 smokers). Each underwent neuropsychological assessment and MRI (structural and resting-state functional). Seed-based functional analyses in anterior and posterior insula were performed to calculate the functional connectivity (FC) with voxels in whole brain. Mixed-effect analyses were performed to explore the interactive effects on smoking and cognitive status. Associations between FCand neuropsychological scales were assessed. Results Mixed-effect analyses revealed the FC differences between the right anterior insula (RAI) with the left middle temporal gyrus (LMTG) and that with the right inferior parietal lobule (RIPL) (p < 0.01). The FC of RAI in both LMTG and RIPL sees a significant decrease in MCI smokers (p< 0.01). Furthermore, the FC between RAI and RIPL was associated with processing speed (r = -0.35, p = 0.003) and execution (r = -0.45, p< 0.001)in smokers. Conclusion Smoking affects insular FC differently between MCI and CN, and could decrease the insula FC in MCI patients. Our study provides evidence of neural mechanisms between smoking and AD.

Airway smooth muscle (ASM) has developed a mechanical adaption mechanism by which it transduces force and responds to environmental forces, which is essential for periodic breathing. Cytoskeletal reorganization has been implicated in this process, but the regulatory mechanism remains to be determined. We here observe that ASM abundantly expresses cytoskeleton regulators Limk1 and Limk2, and their expression levels are further upregulated in chronic obstructive pulmonary disease (COPD) animals. By establishing mouse lines with deletions of Limk1 or Limk2, we analyse the length-sensitive contraction, F/G-actin dynamics, and F-actin pool of mutant ASM cells. As LIMK1 phosphorylation does not respond to the contractile stimulation, LIMK1-deficient ASM develops normal maximal force, while LIMK2 or LIMK1/LIMK2 deficient ASMs show approximately 30% inhibition. LIMK2 deletion causes a significant decrease in cofilin phosphorylation along with a reduced F/G-actin ratio. As LIMK2 functions independently of cross-bridge movement, this observation indicates that LIMK2 is necessary for F-actin dynamics and hence force transduction. Moreover, LIMK2-deficient ASMs display abolishes stretching-induced suppression of 5-hydroxytryptamine (5-HT) but not acetylcholine-evoks force, which is due to the differential contraction mechanisms adopted by the agonists. We propose that LIMK2-mediated cofilin phosphorylation is required for membrane cytoskeleton reorganization that is necessary for ASM mechanical adaption including the 5-HT-evoked length-sensitive effect.

Astragaloside IV (AS-IV) is a chemical found in traditional Chinese medicine called Astragalus membranaceus (Fisch.) Bunge that has antitumor properties. However, the roles and mechanisms of AS-IV in uterine leiomyomas (ULMs) are unclear. The immunosuppressive enzyme indoleamine-2,3-dioxygenase-1 (IDO1) is involved in tumor formation. IDO1 is a new and reliable prognostic indicator for several cancers. In this work, AS-IV was applied to ULM cells in various concentrations. CCK-8, immunofluorescence, and flow cytometry were used to examine the proliferation and apoptosis of ULM cells caused by AS-IV. After lentiviral vector transduction with IDO1 short hairpin RNA (shRNA), the knockdown and overexpression of IDO1 were stable in ULM cells. To verify the antitumor effect of AS-IV in vivo, we established a rat model of uterine leiomyoma. HE staining, Masson staining, and transmission electron microscopy were used to observe pathological changes in the uterus, and the levels of serum sex hormones were measured by radio immune assay (RIA). The levels of CD3+T, CD4+T, and CD25+ Foxp3+Treg in rat peripheral blood were detected by flow cytometry. Western blotting and immunohistochemistry were used to examine protein expression. We found that AS-IV dramatically increased the apoptotic rate of ULM cells and reduced viability in a time- and dosage-dependent manner. After sh-IDO1 lentiviral transfection, we discovered that knocking down IDO1 reversed the effects of AS-IV on ULM cell proliferation and autophagy. We also found that AS-IV can effectively inhibit the growth of ULMs in vivo. AS-IV may promote apoptosis and autophagy in ULMs by activating PTEN/PI3K/AKT signaling through inhibition of IDO1. These findings imply that AS-IV exerts antifibroid effects, and the underlying mechanism may be IDO1, which is involved in proliferation, apoptosis, and autophagy.

Investors have been increasing their allocations to private assets, seeking higher returns and better portfolio diversification. However, as this allocation increases, the liquidity characteristics of their portfolios change. The authors create a framework that links bottom-up private asset investing with top-down asset allocation. Private asset cash flows are consistently modeled together with public asset returns and risk that, in turn, drive portfolio construction. This helps investors analyze how allocations to illiquid private assets, in combination with their commitment strategy, may affect their portfolio’s ability to respond to various liquidity demands. By measuring the potential trade-off among asset allocations, total portfolio performance, and the frequency of certain liquidity events with different severities, this framework can help investors quantify the interaction between their portfolio structure and performance and formalize their decision making around portfolio liquidity choices. TOPICS:Real assets/alternative investments/private equity, portfolio construction, performance measurement, tail risks Key Findings ▪ We present a framework to systematically address various liquidity issues for multi-asset portfolios. ▪ Liquidity requirements have a clear impact on portfolio structure and expected performance. ▪ Commitment pacing of private investments plays a crucial role in the trade-off between liquidity and performance.

Sophisticated investors rely on scenario analysis to select portfolios. We propose a new approach to scenario analysis that enables investors to consider sequential outcomes. We define scenarios no...

Saccharides from Arctium lappa. L. root (ALR-S) is a high-purity fructosaccharide separated from the medicinal plant Arctium lappa. L. root. These compounds showed many pharmacological effects in previous studies. In the present study, the antithrombotic effects of ALR-S in arterial thrombosis via inhibiting platelet adhesion and rebalancing thrombotic and antithrombotic factor expression and secretion were found in rats and human aortic endothelial cells (HAECs). This study also showed that inhibition of oxidative stress (OS), which is closely involved in the expression of coagulation- and thrombosis-related proteins, was involved in the antithrombotic effects of ALR-S. Furthermore, studies using FeCl3-treated HAECs showed that ALR-S induced the abovementioned effects at least partly by blocking the ERK/NF-κB pathway. Moreover, U0126, a specific inhibitor of ERK, exhibited the same effects with ALR-S on a thrombotic process in FeCl3-injured HAECs, suggesting the thrombotic role of the ERK/NF-κB pathway and the antithrombotic role of blocking the ERK/NF-κB pathway by ALR-S. In conclusion, our study revealed that the ERK/NF-κB pathway is a potential therapeutic target in arterial thrombosis and that ALR-S has good characteristics for the cure of arterial thrombosis via regulating the ERK/NF-κB signaling pathway.

Cigarette smoking is a modifiable risk factor for Alzheimer's disease (AD), and controlling risk factors may curb the progression of AD. However, the underlying neural mechanisms of the effects of smoking on cognition remain largely unclear. Therefore, we aimed to explore the interaction effects of smoking × cognitive status on cortico-striatal circuits, which play a crucial role in addiction and cognition, in individuals without dementia.We enrolled 304 cognitively normal (CN) non-smokers, 44 CN smokers, 130 mild cognitive impairment (MCI) non-smokers, and 33 MCI smokers. The mixed-effect analysis was performed to explore the interaction effects between smoking and cognitive status (CN vs. MCI) based on functional connectivity (FC) of the striatal subregions (caudate, putamen, and nucleus accumbens [NAc]).The significant interaction effects of smoking × cognitive status on FC of the striatal subregions were detected in the left inferior parietal lobule (IPL), bilateral cuneus, and bilateral anterior cingulate cortex (ACC). Specifically, increased FC of right caudate to left IPL was found in CN smokers compared with non-smokers. The MCI smokers showed decreased FC of right caudate to left IPL and of right putamen to bilateral cuneus and increased FC of bilateral NAc to bilateral ACC compared with CN smokers and MCI non-smokers. Furthermore, a positive correlation between FC of the NAc to ACC with language and memory was detected in MCI smokers.Cigarette smoking could affect the function of cortico-striatal circuits in patients with MCI. Our findings suggest that quitting smoking in the prodromal stage of AD may have the potential to prevent disease progression.

Background: Mild cognitive impairment (MCI) is the prodromal phase of Alzheimer’s disease (AD) and has a high risk of progression to AD. Cigarette smoking is one of the important modifiable risk factors in AD progression. Cholinergic dysfunction, especially the nucleus basalis of Meynert (NBM), is the converging target connecting smoking and AD. However, how cigarette smoking affects NBM connectivity in MCI remains unclear.Objective: This study aimed to evaluate the interaction effects of condition (non-smoking vs. smoking) and diagnosis [cognitively normal (CN) vs. MCI] based on the resting-state functional connectivity (rsFC) of the NBM.Methods: After propensity score matching, we included 86 non-smoking CN, 44 smoking CN, 62 non-smoking MCI, and 32 smoking MCI. All subjects underwent structural and functional magnetic resonance imaging scans and neuropsychological tests. The seed-based rsFC of the NBM with the whole-brain voxel was calculated. Furthermore, the mixed effect analysis was performed to explore the interaction effects between condition and diagnosis on rsFC of the NBM.Results: The interaction effects of condition × diagnosis on rsFC of the NBM were observed in the bilateral prefrontal cortex (PFC), bilateral supplementary motor area (SMA), and right precuneus/middle occipital gyrus (MOG). Specifically, the smoking CN showed decreased rsFC between left NBM and PFC and increased rsFC between left NBM and SMA compared with non-smoking CN and smoking MCI. The smoking MCI showed reduced rsFC between right NBM and precuneus/MOG compared with non-smoking MCI. Additionally, rsFC between the NBM and SMA showed a significant negative correlation with Wechsler Memory Scale-Logical Memory (WMS-LM) immediate recall in smoking CN (r = −0.321, p = 0.041).Conclusion: Our findings indicate that chronic nicotine exposure through smoking may lead to functional connectivity disruption between the NBM and precuneus in MCI patients. The distinct alteration patterns on NBM connectivity in CN smokers and MCI smokers suggest that cigarette smoking has different influences on normal and impaired cognition.

To explore the interaction effects of smoking status (non-smoking vs. smoking) and disease (cognitively normal (CN) vs. MCI) based on resting-state functional connectivity (rsFC) of the corticostriatal circuits. We included 304 CN non-smokers, 44 CN smokers, 130 MCI non-smokers, and 33 MCI smokers. The seed-based rsFC of striatal subregions (caudate, putamen, and nucleus accumbens [NAc]) with the whole-brain voxel was calculated. Furthermore, we performed mixed effect analysis to explore the interaction effects between smoking status and disease. Significant interaction effects were detected between: (1) right caudate and left inferior parietal lobule (IPL); (2) right putamen and bilateral cuneus; (3) bilateral NAc and bilateral anterior cingulate cortex (ACC). The post-hoc analyses revealed that the CN smokers showed increased rsFC between right caudate and left IPL compared to non-smokers; while the MCI smokers demonstrated decreased rsFC between right putamen and cuneus, and increased rsFC between bilateral NAc and ACC compared to non-smokers. In MCI smokers, the rsFC value between left NAc and ACC was positively correlated with Semantic Verbal Fluency (SVF, r = 0.387, p = 0.026), and the rsFC value between right NAc and ACC was positively correlated with SVF (r = 0.390, p = 0.025), Wechsler memory scale-logical memory (WMS-LM) immediate recall (r = 0.378, p = 0.03), and WMS-LM delayed recall (r = 0.367, p = 0.036). Our findings suggest that chronic nicotine exposure may lead to functional connectivity alterations of corticostriatal circuits in MCI patients, and the pattern is different from CN smokers.

Vehicle detection is an essential part of an intelligent traffic system, which is an important research field in drone application. Because unmanned aerial vehicles (UAVs) are rarely configured with stable camera platforms, aerial images are easily blurred. There is a challenge for detectors to accurately locate vehicles in blurred images in the target detection process. To improve the detection performance of blurred images, an end-to-end adaptive vehicle detection algorithm (DCNet) for drones is proposed in this article. First, the clarity evaluation module is used to determine adaptively whether the input image is a blurred image using improved information entropy. An improved GAN called Drone-GAN is proposed to enhance the vehicle features of blurred images. Extensive experiments were performed, the results of which show that the proposed method can detect both blurred and clear images well in poor environments (complex illumination and occlusion). The detector proposed achieves larger gains compared with SOTA detectors. The proposed method can enhance the vehicle feature details in blurred images effectively and improve the detection accuracy of blurred aerial images, which shows good performance with regard to resistance to shake.

ObjectivesCurdione is one of the active ingredients of a traditional Chinese herbal medicine-Curcuma zedoary and established anti-tumor effects. Uterine leiomyosarcoma (uLMS) is a rare gynecological malignancy, with no standard therapeutic regimen at present. The aim of this study was to explore the potential anti-tumor impact of curdione in uLMS and elucidate the underlying mechanisms.MethodsIn vitro functional assays were performed in the SK-UT-1 and SK-LMS-1 cell lines. The in vivo model of uLMS was established by subcutaneously injecting SK-UT-1 cells, and the tumor-bearing mice were intraperitoneally injected with curdione. Tumor weight and volume were measured at specific time points. The biosafety was evaluated by monitoring changes of body weight and the histopathology in the liver and kidney. The expression levels of relevant proteins were analyzed by western blotting and immunohistochemistry.ResultsCurdione decreased the viability and proliferation of uLMS cells in a concentration and time-dependent manner. In addition, the curdione-treated cells exhibited significantly higher rates of apoptosis and autophagic death. Curdione also decreased the tumor weight and volume in the SK-UT-1 xenograft model compared to the untreated control without affecting the body bodyweight or pathological injury of liver and kidney tissues. At the molecular level, the anti-tumor effects of curdione were mediated by indoleamine-2, 3-dioxygenase-1 (IDO1).ConclusionCurdione exhibited an anti-uLMS effect in vitro and in vivo; the underlying mechanism involved in IDO1 mediate apoptosis, autophagy, and G2/M phase arrest.

Institutional portfolios are increasing allocations to illiquid private assets seeking better returns and diversification. However, as allocations increase, a portfolio’s liquidity structure changes, sometimes abruptly. How can a CIO increase their confidence with private asset allocations and unlock their potential? Using a corporate defined benefit pension plan as our example, we present and illustrate a practical framework (OASIS TM) that can help CIOs analyze how their top-down asset allocation and their bottom-up private investing activity interact to affect their portfolio’s ability to respond to liquidity demands in a multi-asset, multi-period setting. This is exactly what a CIO needs to know. Besides scheduled benefit payments, corporate pension plans have many unexpected liquidity demands which should be accounted for when evaluating liquidity risk. For example, a plan should be able to rebalance when market movements cause allocations to exceed risk limits. A plan also needs liquidity to meet unexpected capital calls and be prepared for exogenous cash flow events driven by corporate actions (e.g., pension risk transfers, corporate contributions, and merger and acquisition activities). Many plans also have asset allocation glide paths, conditional on the plan’s funding ratio, that present additional liquidity strains as it may be difficult to sell illiquid assets to satisfy new allocation targets. The CIO’s challenge is to maximize expected portfolio performance while keeping liquidity risk under control. By measuring the potential tradeoff between asset allocation, portfolio performance and multiple dimensions of liquidity risk, the OASIS framework can help CIOs make more informed portfolio management decisions.

Background Curdione, one of active ingredients of a traditional Chinese herb medicine-Curcuma zedoary, has been reported with beneficial therapeutic effects in lots of cancer types. However, the potential anti-cancer effect in uterine leiomyosarcoma (uLMS) and the underlying mechanisms are still unclear.Methods The aim of this study was to explore the potential effect and mechanisms of curdione on uLMS in vitro and vivo with uLMS cell lines and mouse xenograft tumor model respectively.Results Curdione triggered anti-proliferation effect in uLMS cell lines by inducing cell cycle arrest at G2/M phase, caspase-mediated cell apoptosis, and pro-death cell autophagy. Indoleamine-2,3-dioxygenase-1 (IDO1), which was dependent on cyclooxygenase-2 (COX2), mediated the anti-proliferation effect of curdione. Curdione down-regulated IDO1 expression and promoted the dephosphorylation of protein kinase c (PKC), glycogen synthase kinase-3 beta (GSK3β) and β-catenin in cell lines. PKC/GSK3β/β-catenin pathway responsible for constitutive IDO1 expression in uLMS. COX2 mediate the promotion effect of curdione on the PKC/GSK3β/β catenin pathway activity, which was detected by COX2 inhibitor, and further confirmed by COX2 siRNA and COX2 overexpression. The pathway activity was inhibited by COX2-siRNA and enhanced by COX2 overexpression. In turn, the pathway inhibitor suppressed IDO1 expression. The anti-proliferation effect of curdione on uterine leiomyosarcoma were further confirmed in vivo. Echoing to the results in vitro, the underline mechanism involved in COX2-mediated IDO1 down-regulation via PKCδ/GSK3β/β-catenin pathway.Conclusion COX2-mediated IDO1 down-regulation via PKCδ/GSK3β/β-catenin pathway involved in the anti-proliferation effect of curdione on uterine leiomyosarcoma in vitro and vivo.

Metaflammation is a primary inflammatory complication of metabolic disorders characterized by altered production of many inflammatory cytokines, adipokines, and lipid mediators. Whereas multiple inflammation networks have been identified, the mechanisms by which metaflammation is initiated have long been controversial. As the mevalonate pathway (MVA) produces abundant bioactive isoprenoids and abnormal MVA has a phenotypic association with inflammation/immunity, we speculate that isoprenoids from the MVA may provide a causal link between metaflammation and metabolic disorders. Using a line with the MVA isoprenoid producer geranylgeranyl diphosphate synthase (GGPPS) deleted, we find that geranylgeranyl pyrophosphate (GGPP) depletion causes an apparent metaflammation as evidenced by abnormal accumulation of fatty acids, eicosanoid intermediates, and proinflammatory cytokines. We also find that GGPP prenylate cytochrome b(5) reductase 3 (CYB5R3) and the prenylated CYB5R3 then translocate from the mitochondrial to the endoplasmic reticulum (ER) pool. As CYB5R3 is a critical NADH-dependent reductase necessary for eicosanoid metabolism in ER, we thus suggest that GGPP-mediated CYB5R3 prenylation is necessary for metabolism. In addition, we observe that pharmacological inhibition of the MVA pathway by simvastatin is sufficient to inhibit CYB5R3 translocation and induces smooth muscle death. Therefore, we conclude that the dysregulation of MVA intermediates is an essential mechanism for metaflammation initiation, in which the imbalanced production of eicosanoid intermediates in the ER serve as an important pathogenic factor. Moreover, the interplay of MVA and eicosanoid metabolism as we reported here illustrates a model for the coordinating regulation among metabolite pathways.

Tooth instance segmentation provides important assistance for computer-aided orthodontic treatment. Many previous studies on this issue have limited performance on distinguishing adjacent teeth and obtaining accurate tooth boundaries. To address the challenging task, in this paper, we present a novel method achieving tooth instance segmentation and classification from cone beam CT (CBCT) images. The core of our method is a two-level hierarchical deep neural network. We first embed center-sensitive mechanism with global stage heatmap, so as to ensure accurate tooth centers and guide the localization of tooth instances. Then in the local stage, DenseASPP-UNet is proposed for fine segmentation and classification of individual tooth. Further, in order to improve the accuracy of tooth segmentation boundary and refine the boundaries of overlapped teeth, a boundary-aware dice loss and a novel label optimization are also applied in our method. Comparative experiments show that the proposed framework exhibits high segmentation performance and outperforms the state-of-the-art methods.

Constructing porous structure has proved to be an effective strategy to improve the gas sensing properties of metal oxide semiconducting materials. In this work, high-performance hydrogen sulfide (H2S) gas sensing material with porous structure were synthesized by growing nickel oxide (NiO) on vanadium trioxide (V2O3) seeds. Morphology and structure characterizations reveal that the novel three-dimensional (3D) nanoflowers are formed by self-assembling two-dimensional (2D) porous nanosheets with high surface area and abundant active sites. Compared with pristine NiO, the sensing performance of V2O3-NiO (VN8, VN7, VN6) with different ratios of V3+: Ni2+ is enhanced due to their porous structure. Among them, VN7 sensor shows excellent sensing properties at 200 °C. The response to 500 ppb H2S can reach 65, which increases as high as 2.2 times compared with the pristine NiO sensor. The response time to 500 ppb H2S is further decreased from 13 s of the pristine NiO sensors to 8 s of VN7 sensor. The VN7 sensor also shows a wide linear range from 20 ppb to 500 ppb, high selectivity, good repeatability, long-term stability, moisture resistance and low detection limit (20 ppb), indicating its potential candidate for ppb-level H2S detection in complex environment of industrial mine.

The APOE ε4 allele is associated with impaired intrinsic functional connectivity in neural networks, especially in the default mode network (DMN). However, effective connectivity (EC) reflects the direct causal effects of one brain region to another, which has rarely been investigated. Recently, Granger causality analysis (GCA) proved suitable for the study of directionality in neuronal interactions. Using GCA, we examined the differences in the EC between the anterior medial prefrontal cortex/posterior cingulate cortex (aMPFC/PCC) and the whole brain in 17 ε4 carrying and 32 non-carrying cognitively intact elderly individuals. Furthermore, correlation analyses were performed between the abnormal EC and cognition/neuropathological indices. Compared with the non-carriers, the results showed that the ε4 carriers exhibited decreased EC from the PCC to the whole brain in the middle temporal gyrus (MTG), the anterior cingulate cortex (ACC), and the precuneus (PCu). Meanwhile, the ε4 carriers demonstrated increased EC from the whole brain to the aMPFC in the inferior parietal lobe (IPL) and the postcentral gyrus (PCG). The correlation analyses suggested that the EC from the IPL/PCG to the aMPFC was related to episodic memory in non-carriers, while the decreased EC from the PCC to the ACC was associated with increased levels of t-tau in the ε4 carriers. In ε4 carriers, a negative influence can be traced from the PCC to both the anterior and posterior DMN subsystems; meanwhile, the anterior DMN subsystem receives compensatory effects from the parietal cortex. Early increases in AD-related pathologies in the PCC may act as first factors during this pathological process.

Tobacco use disorder is frequently comorbid with emotional disorders, each exerting reciprocal influence on the other. As an important hub for emotional processing, amygdala may also play a critical role in tobacco addiction. Therefore, we aimed to investigate the volume and spontaneous activity of the amygdala in nicotine-dependent individuals and their relationships with cigarette use. A total of 84 smokers (aged 22-54 years) and 41 nonsmokers (aged 26-56 years) were enrolled in the present study. 3D-T1 weighted images and resting-state fMRI images were acquired from all participants. We used ROI-wise volume, fractional amplitude of low frequency fluctuation (fALFF) and resting-state functional connectivity (FC) to assess structural and functional changes of the amygdala in the smokers. There was no significant difference between smokers and nonsmokers on amygdala volume (p > 0.05). When compared to nonsmokers, increased fALFF in the right amygdala was observed in smokers (p = 0.024). In addition, increased FC between the left amygdala and the right precuneus and decreased FC between the right amygdala and the right orbitofrontal cortex (OFC) was found in smokers. In smokers, these amygdala measures did not correlate with any measures of cigarette use. The results revealed that the amygdala function but not volume was affected in nicotine addiction. When considering the fALFF and FC results, we propose that the OFC top-down control may regulate the amygdala activity in nicotine addicts. The pattern of amygdala-based FC in smokers revealed in our study may provide new information about the brain circuitry of tobacco dependence.

Three pyrazole-3-carboxylic acid (H 2 pca) complexes, Cr(Hpca) 3 ·2H 2 O ( 1 ), Ni 2 (pca) 2 (H 2 O) 6 ·2H 2 O ( 2 ) and [Pb 2 (Hpca) 4 ] n ( 3 ), have been synthesized and fully characterized. The single crystal X-ray diffraction indicate that the mononuclear Cr(III) cation in complex 1 and binuclear Ni(II) cations in complex 2 are coordinated by pyrazole-3-carboxylic acid ligands and water molecules in a distorted octahedral geometry and the binuclear Pb(II) cations in complex 3 presents a distorted seven-coordinated {PbN2O5} pentagonal-bipyramid geometry. Notably, these complexes as effective heterogeneous catalysts show efficient catalytic activities for Knoevenagel condensation (yield up to 97%) and the catalyst can be recycled without losing activity.

// Xiao Luo 1, * , Yerfan Jiaerken 1, * , Xinfeng Yu 1 , Peiyu Huang 1 , Tiantian Qiu 1 , Yunlu Jia 3 , Kaicheng Li 1 , Xiaojun Xu 1 , Zhujing Shen 1 , Xiaojun Guan 1 , Jiong Zhou 2 and Minming Zhang 1 , for The Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1 Department of Radiology, The Second Affiliated Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China 2 Department of Neurology, The Second Affiliated Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China 3 Department of Surgical Oncology, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, China * These authors have contributed equally to this work Correspondence to: Minming Zhang, email: zhangminming@zju.edu.cn Keywords: apolipoprotein E (APOE), cerebral small-vascular disease (CSVD), white matter hyperintensities (WMH), dilated perivascular space (dPVS), cognition Abbreviations: APOE: apolipoprotein E; CSVD: cerebral small-vascular disease; WMH: white matter hyperintensities; dPVS: dilated perivascular space; MBs: microbleeds Received: December 29, 2016 Accepted: April 07, 2017 Published: May 09, 2017 ABSTRACT Objective: It remains unclear if and how the interactions between APOE genotypes and cerebral small-vessel diseases (CSVD) lead to cognitive decline in the long term. Based on ADNI cohort, this longitudinal study aimed to clarify the potential relationship among APOE genotype, CSVD and cognition by integrating multi-level data. Method: There were 135 healthy elderly (including e2, e4 allele carriers and e3 homozygotes) who had completed two years’ follow-up. MRI markers of CSVD, including white matter hyperintensities (WMH), dilated perivascular space (dPVS), microbleeds and lacune, were assessed. Besides, neuropathological factors including Alzheimer’s disease-related pathology measured by CSF and PiB-PET were assessed. Repeated measurements ANOVAs were performed to test impact of different APOE genotypes on CSVD. Results: We found that APOE e4 carriers had significantly more frontal WMH burden and basal ganglia dPVS at baseline and faster progression of frontal WMH burden during follow-up. Furthermore, our results showed that APOE e4 carriers had significantly decreased Aβ 1-42 level, and its level was negatively related with baseline and progressive total WMH burden. Then, general linear modals indicated interaction between basal frontal WMH burden and e4 allele was related with declining trend of cognition. Conclusion: Our findings suggested APOE e4 allele was associated with increased Aβ deposition, which may lead to the formation and progression of WMH, especially in frontal lobe. Besides, interaction between the increased frontal WMH burden and e4 allele can exert long-term detrimental effects on individual’s trajectory of cognition.

Investors have been increasing their allocations to private assets seeking higher returns and better portfolio diversification. However, as this allocation increases, the liquidity characteristics of their portfolios change. To address this issue we create a framework that links bottom-up private asset investing with top-down asset allocation. Private asset cash flows are consistently modeled together with public asset returns and risk that, in turn, drive portfolio construction. This helps investors analyze how allocations to illiquid private assets, in combination with their commitment strategy, may affect their portfolio’s ability to respond to various liquidity demands. By measuring the potential tradeoff between asset allocations, total portfolio performance and the frequency of certain liquidity events with different severities, this framework can help investors quantify the interaction between their portfolio structure and performance, and formalize their decision making around portfolio liquidity choices.

Saccharides from Arctium lappa. L. root (ALR-S) is a high-purity fructosaccharide separated from the medicinal plant Arctium lappa. L. root. These compounds showed many pharmacological effects in previous studies. In the present study, the antithrombotic effects of ALR-S in arterial thrombosis via inhibiting platelet adhesion and rebalancing thrombotic and antithrombotic factor expression and secretion were found in rats and human aortic endothelial cells (HAECs). This study also showed that inhibition of oxidative stress (OS), which is closely involved in the expression of coagulation- and thrombosis-related proteins, was involved in the antithrombotic effects of ALR-S. Furthermore, studies using FeCl3-treated HAECs showed that ALR-S induced the abovementioned effects at least partly by blocking the ERK/NF-κB pathway. Moreover, U0126, a specific inhibitor of ERK, exhibited the same effects with ALR-S on a thrombotic process in FeCl3-injured HAECs, suggesting the thrombotic role of the ERK/NF-κB pathway and the antithrombotic role of blocking the ERK/NF-κB pathway by ALR-S. In conclusion, our study revealed that the ERK/NF-κB pathway is a potential therapeutic target in arterial thrombosis and that ALR-S has good characteristics for the cure of arterial thrombosis via regulating the ERK/NF-κB signaling pathway.

Hydrogen sulfide（H2S）is a colorless and odorous gas. Abnormal H2S concentration may be related to Alzheimer's disease, ischemia, Down syndrome, bad breath and other diseases. Therefore, rapid、sensitive and highly selective detection of H2S is essential for the early diagnosis of these diseases. In the research, a two-dimensional nanosheet self-assembly structure based on NiO-V2O3 was developed to construct a high-performance H2S gas sensor. Morphological and structural characterization proved that the NiO-V2O3 composite is a three-dimensional flower-like porous microspheres self-assembled from two-dimensional nanosheets with high surface area and rich active sites. The sensor can quantitatively detect H2S gas at ppb level. When exposed to 500 ppb H2S gas at the optimal working temperature of 200°C, the highest response of the sensor is 65, and the response time and recovery time are 8 s and 25 s, respectively. The sensor also has excellent stability, moisture resistance and selectivity, and has a low detection limit (20 ppb). Considering these advantages, the NiO-V2O3 sensor is expected to be used for the detection of H2S in the early diagnosis of certain diseases. Figure 1

Mild cognitive impairment (MCI) is a heterogeneous condition associated with a high risk of progressing to Alzheimer's disease (AD). Although functional brain network alterations have been observed in progressive MCI (pMCI), the underlying pathological mechanisms of network alterations remain unclear. In the present study, we evaluated neuropsychological, imaging, and cerebrospinal fluid (CSF) data at baseline across a cohort of: 21 pMCI patients, 33 stable MCI (sMCI) patients, and 29 normal controls. Fast eigenvector centrality mapping (fECM) based on resting-state functional MRI (rsfMRI) was used to investigate brain network organization differences among these groups, and we further assessed its relation to cognition and AD-related pathology. Our results demonstrated that pMCI had decreased eigenvector centrality (EC) in left temporal pole and parahippocampal gyrus, and increased EC in left middle frontal gyrus compared to sMCI. In addition, compared to normal controls, patients with pMCI showed decreased EC in right hippocampus and bilateral parahippocampal gyrus, and sMCI had decreased EC in right middle frontal gyrus and superior parietal lobule. Correlation analysis showed that EC in the left temporal pole was related to Wechsler Memory Scale-Revised Logical Memory (WMS-LM) delay score (r = 0.467, p = 0.044) and total tau (t-tau) level in CSF (r = -0.509, p = 0.026) in pMCI. Our findings implicate EC changes of different brain network nodes in the prognosis of pMCI and sMCI. Importantly, the association between decreased EC of brain network node and pathological changes may provide a deeper understanding of the underlying pathophysiology of pMCI.

Herein, we described 2 patients with posterior spinal artery syndrome (PSAS) caused by vertebral artery dissection. The patients complained of sudden neck pain or walking instability. Neurological examination revealed sensory loss, muscle weakness, and sensory ataxia. Angiography showed double lumen sign or intimal flap in the vertebral artery. T2-weighted imaging and diffusion-weighted imaging of MRI showed a hyperintense lesion in the dorsal side of the cervical spinal cord at different times after onset. Both patients had good outcome after antiplatelet therapy and physiotherapy. A review of previously reported PSAS cases was also conducted in order to improve the understanding and awareness of this rare myelopathy.

The apolipoprotein E (APOE) ɛ4 allele is the best-known genetic risk factor for developing sporadic Alzheimer's disease (AD). According to neuroimaging studies, the APOE ɛ4 allele is associated with localized altered brain function. However, in long-range circuitry, APOE ɛ4 allele-related alterations in functional communication between hemispheres have rarely been directly investigated. We examined the alteration of resting-state functional connectivity (RSFC) between inter-hemispheric homotopic regions in cognitively intact, elderly APOE ɛ4 carriers. The voxel-mirrored homotopic connectivity method was used to assess the inter-hemispheric RSFC. The current study included 13 cognitively intact, elderly APOE ɛ4 carriers (with at least one copy of APOE ɛ4 allele) and 22 well-matched ɛ3 homozygotes. Comparisons between the two groups were conducted, and subsequently, the correlation between the differential inter-hemispheric RSFC and cognitive ability was analyzed. Compared with ɛ3 homozygotes, APOE ɛ4 carriers showed decreased inter-hemispheric RSFC in the bilateral medial temporal lobe (MTL) and orbital frontal cortex (OFC). Moreover, in APOE ɛ4 carriers, the inter-hemispheric RSFC of the MTL correlated with the Wechsler Memory Scale-Logical Memory (WMS-LM) (immediate and delayed performance, r = 0.64, p < 0.05; r = 0.65, p < 0.05, respectively), and the inter-hemispheric RSFC of the OFC correlated with the WMS-LM delayed performance (r = 0.71, p < 0.05). In our study, the presence of the APOE ɛ4 allele was linked with decreased inter-hemispheric RSFC, which was attributed to memory performance in carriers.

Background: Amnestic mild cognitive impairment (aMCI) is a heterogeneous condition. Based on clinical symptoms, aMCI could be categorized into single-domain aMCI (SD-aMCI, only memory deficit) and multi-domain aMCI (MD-aMCI, one or more cognitive domain deficit). As core intrinsic functional architecture, inter-hemispheric connectivity maintains many cognitive abilities. However, few studies investigated whether SD-aMCI and MD-aMCI have different inter-hemispheric connectivity pattern.Methods: We evaluated inter-hemispheric connection pattern using fluorine-18 positron emission tomography – fluorodeoxyglucose (18F PET-FDG), resting-state functional MRI and structural T1 in 49 controls, 32 SD-aMCI, and 32 MD-aMCI patients. Specifically, we analyzed the 18F PET-FDG (intensity normalized by cerebellar vermis) in a voxel-wise manner. Then, we estimated inter-hemispheric functional and structural connectivity by calculating the voxel-mirrored homotopic connectivity (VMHC) and corpus callosum (CC) subregions volume. Further, we correlated inter-hemispheric indices with the behavioral score and pathological biomarkers.Results: We found that MD-aMCI exhibited more several inter-hemispheric connectivity damages than SD-aMCI. Specifically, MD-aMCI displayed hypometabolism in the bilateral middle temporal gyrus (MTG), inferior parietal lobe, and left precuneus (PCu) (p < 0.001, corrected). Correspondingly, MD-aMCI showed decreased VMHC in MTG, PCu, calcarine gyrus, and postcentral gyrus, as well as smaller mid-posterior CC than the SD-aMCI and controls (p < 0.05, corrected). Contrary to MD-aMCI, there were no neuroimaging indices with significant differences between SD-aMCI and controls, except reduced hypometabolism in bilateral MTG. Within aMCI patients, hypometabolism and reduced inter-hemispheric connectivity correlated with worse executive ability. Moreover, hypometabolism indices correlated to increased amyloid deposition.Conclusion: In conclusion, patients with MD-aMCI exhibited the more severe deficit in inter-hemispheric communication than SD-aMCI. This long-range connectivity deficit may contribute to cognitive profiles and potentially serve as a biomarker to estimate disease progression of aMCI patients.

Summary Background There is a growing literature documenting a variety of brain abnormalities associated with obesity. However, little is known about the effects of obesity on inter-hemispheric connectivity in aging people. Methods Participants included 61 cognitively intact elderly (including people with obesity, overweight, and lean controls) who underwent structural MRI, resting-state functional magnetic resonance imaging (rsfMRI) and standard neuropsychological batteries. Techniques including FreeSurfer and Voxel-mirrored Homotopic Connectivity (VMHC) were employed to evaluate inter-hemispheric structural and functional connectivity respectively. Results There were no differences of cognitive abilities and vascular risks among groups. When compared to lean controls, obese group had greater VMHC in fusiform gyrus (FG); while overweight group had greater VMHC in FG, calcarine gyrus, inferior temporal gyrus (ITG), and postcentral gyrus (PCG). Moreover, the obesity group had lower VMHC in calcarine gyrus and PCG than overweight group (p Conclusions The present study suggested, increased inter-hemispheric information transmission in networks supporting visual and sensorimotor function may lead to gain in weight, by possibly mediating diet behaviours of individuals.

Peripheral primitive neuroectodermal tumor (pPNET) is a rare and highly malignant undifferentiated tumor, which presents in infants and young adults. pPNETs in the head and neck region are uncommon and have a varying incidence of occurrence. Peripheral PNETs of the maxilla and mandible are particularly rare. At present, only 16 cases of pPNET of the maxilla and 13 cases of pPNET of the mandible have been reported. The present study describes a case of pPNET of the maxilla in a 16-year-old male and a case of pPNET of the mandible in another 16-year-old male. The present study reports the radiological findings and the clinical courses of the two patients.

Amnestic mild cognitive impairment can be further classified as single-domain aMCI (SD-aMCI) with isolated memory deficit, or multi-domain aMCI (MD-aMCI) if memory deficit is combined with impairment in other cognitive domains. Prior studies reported these clinical subtypes presumably differ in etiology. Thus, we aimed to explore the possible mechanisms between different aMCI subtypes by assessing alteration in brain activity and brain vasculature, and their relations with CSF AD biomarkers. 49 healthy controls, 32 SD-aMCI, and 32 MD-aMCI, who had undergone structural scans, resting-state functional MRI (rsfMRI) scans and neuropsychological evaluations, were identified. Regional homogeneity (ReHo) was employed to analyze regional synchronization. Periventricular white matter hyperintensities (PWMH) and deep WMH (DWMH) volume of each participant was quantitatively assessed. AD biomarkers from CSF were also measured. SD-aMCI showed decreased ReHo in medial temporal gyrus (MTG), and increased ReHo in lingual gyrus (LG) and superior temporal gyrus (STG) relative to controls. MD-aMCI showed decreased ReHo, mostly located in precuneus (PCu), LG and postcentral gyrus (PCG), relative to SD-aMCI and controls. As for microvascular disease, MD-aMCI patients had more PWMH burden than SD-aMCI and controls. Correlation analyses indicated mean ReHo in differenced regions were related with memory, language, and executive function in aMCI patients. However, no significant associations between PWMH and behavioral data were found. The Aβ level was related with the ReHo value of STG in SD-aMCI. MD-aMCI displayed different patterns of abnormal regional synchronization and more severe PWMH burden compared with SD-aMCI. Therefore aMCI is not a uniform disease entity, and MD-aMCI group may show more complicated pathologies than SD-aMCI group.

Background Iron deposition may contribute to the clinical symptoms in Parkinson's disease (PD). With partial different clinical manifestations, the iron deposition patterns between patients with early-onset Parkinson's disease (EOPD) and middle-late-onset Parkinson's disease (M-LOPD) are still unclear. This study was designed to investigate the patterns of iron deposition and their clinical relevance in EOPD and M-LOPD patients, using quantitative susceptibility mapping technique. Materials and methods Thirty-five EOPD patients and 24 matched young controls, 33 M-LOPD patients and 22 matched older controls were recruited in the study. The iron content in the deep grey matter nuclei in the basal ganglia and midbrain were measured, and compared between patients and their corresponding controls. The correlations of regional iron content and clinical features were explored in patient groups. Results Both M-LOPD and EOPD patients showed increased iron content in the substantia nigra (SN) pars compacta and SN pars reticulata. Increased iron content in the putamen was only observed in M-LOPD patients. The relationship between the increased iron content and disease severity (H&Y stages, UPDRS II scores and UPDRS III scores) was observed in M-LOPD patients, but not in EOPD patients. Conclusion Our study suggested that the iron deposition pattern was greatly influenced by the age of PD onset, which increases our understanding of the different pathological underpinnings of EOPD and M-LOPD patients.

Apolipoprotein E (APOE) e4 allele is the best established genetic risk factor for sporadic Alzheimer’s disease (AD). However, there is a need to understand the effects of this genotype on the brain by simultaneously assessing intrinsic brain network and cerebral spinal fluid (CSF) biomarkers changes in healthy older e4 carriers. Thirteen cognitively intact, elderly APOE e4 carriers and 22 e3 homozygotes were included in the present study. Eigenvector centrality mapping (ECM) was used to identify brain network hub organization based on resting-state functional MRI (rsfMRI). We evaluated comprehensive cognitive ability and tested levels of Aβ1–42, total-tau (t-tau) and phosphorylated-tau (p-tau181) in CSF. Comparisons of ECM between two groups were conducted, followed by correlations analyses between EC values with significant group differences and cognitive ability/CSF biomarkers. APOE e4 carriers showed significantly decreased EC values in left medial temporal lobe (MTL), left lingual gyrus (LG) and increased EC values in left middle frontal gyrus (MFG) as compared to non-carriers. Correlation analysis demonstrated that left LG EC value correlated with Rey Auditory Verbal Learning Test total learning (RAVLT, r = 0.57, p

Background Asymmetric medullary veins (AMV) are frequently observed in stroke patients and single-echo susceptibility weighted imaging (SWIs) is the main technique in detecting AMV. Our study aimed to investigate which echo time (TE) on single-echo susceptibility is the optimal echo for visualizing AMV and to compare the ability in detecting AMV in stroke patients between SWIs and multi-echo susceptibility weighted imaging (SWIc). Materials and methods Twenty patients with middle cerebral artery stroke were included. SWI was acquired by using a multi-echo gradient-echo sequence with six echoes ranging from 5 ms to 35.240 ms. Three different echoes of SWIs including SWIs1 (TE = 23.144 ms), SWIs2 (TE = 29.192 ms) and SWIs3 (TE = 35.240 ms) were reconstructed. SWIc was averaged using the three echoes of SWIs. Image quality and venous contrast of medullary veins were compared between SWIs and SWIc using peak signal-to-noise ratio (PSNR), mean opinion score (MOS), contrast-to-noise ratio (CNR) and signal-to-noise ratio (SNR). The presence of AMV was evaluated in each SWIs (1-3) and SWIc. Results SWIs2 had the highest PSNR, MOS and CNR and SWIs1 had the highest SNR among three different echoes of SWIs. No significant difference was found in SNR between SWIs1 and SWIs2. PSNR, MOS and CNR in SWIc were significantly increased by 27.9%, 28.2% and 17.2% compared with SWIs2 and SNR in SWIc was significantly increased by 32.4% compared with SWIs1. 55% of patients with AMV were detected in SWIs2, SWIs3 and SWIc, while 50% AMV were found in SWIs1. Conclusions SWIs using TE around 29ms was optimal in visualizing AMV. SWIc could improve image quality and venous contrast, but was equal to SWIs using a relative long TE in evaluating AMV. These results provide the technique basis for further research of AMV in stroke.