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Whether water dissociates on a perfect TiO2 surface is unclear. To address this issue, we simulated TiO2–water interfaces with a combination of thermodynamic (i.e., acidity constant) and kinetic (i.e., activation barrier) calculations.

Background According to the new ‘AT(N)’ system, those with a normal amyloid biomarker but with abnormal tauopathy or biomarkers of neurodegeneration or neuronal injury, have been labeled suspected non-Alzheimer’s pathophysiology (SNAP). We aimed to estimate the long-term clinical and cognitive trajectories of SNAP individuals in non-demented elders and its comparison with individual in the Alzheimer’s disease (AD) pathophysiology using ‘AT(N)’ system. Methods We included individuals with available baseline cerebrospinal fluid (CSF) Aβ (A), CSF phosphorylated tau examination (T) and 18F-fluorodeoxyglucose PET or volumetric magnetic resonance imaging (N) from the Alzheimer's Disease Neuroimaging Initiative database. Longitudinal change in clinical outcomes are assessed using linear mixed effects models. Conversion risk from cognitively normal (CN) to cognitively impairment, and conversion from mild cognitive impairment (MCI) to dementia are assessed using multivariate Cox proportional hazard models. Results Totally, 366 SNAP individuals were included (114 A-T-N-, 154 A-T + N-, 54 A-T-N + and 44 A-T + N+) of whom 178 were CN and 188 were MCI. Compared with A-T-N-, CN elders with A-T + N-, A-T-N + and A-T + N + had a faster rate of ADNI-MEM score decline. Moreover, CN older individuals with A-T + N + also had a faster rate of decline in ADNI-MEM score than those with A-T + N- individuals. MCI patients with A-T + N + had a faster rate of ADNI-MEM and ADNI-EF decline and hippocampal volume loss compared with A-T-N- and A-T + N- profiles. CN older individuals with A-T + N + had an increased risk of conversion to cognitive impairment (CDR-GS ≥ 0.5) compared with A-T + N- and A-T-N-. In MCI patients, A-T + N + also had an increased risk of conversion to dementia compared with A-T + N- and A-T-N-. Compared with A-T + N-, CN elders and MCI patients with A + T + N- and A + T + N + had a faster rate of ADNI-MEM score, ADNI-EF score decline, and hippocampal volume loss. CN individuals with A + T + N + had a faster rate of ADNI-EF score decline compare with A-T + N + individuals. Moreover, MCI patients with A + T + N + also had a faster rate of decline in ADNI-MEM score, ADNI-EF score and hippocampal volume loss than those with A-T + N + individuals. Conclusions The findings from clinical, imaging and biomarker studies on SNAP, and its comparison with AD pathophysiology offered an important foundation for future studies.

Room-temperature ionic liquids (RTILs) emerged as ideal solvents, and bipyridine as one of the most used ligands have been widely employed in surface science, catalysis, and molecular electronics. Herein, in situ shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) and STM break junction (STM-BJ) technique has been employed to probe the electrochemical process of bipyridine at Au(111)/IL interfaces. It is interestingly found that these molecules undertake a redox process with a pair of well-defined reversible peaks in cyclic voltammograms (CVs). The spectroscopic evidence shows a radical cation generated with rising new Raman peaks related to parallel CC stretching of a positively charged pyridyl ring. Furthermore, these electrochemically charged bipyridine is also confirmed by electrochemical STM-BJ at the single-molecule level, which displays a binary conductance switch ratio of about 400% at the redox potentials. This present work offers a molecular-level insight into the pyridine-mediated reaction process and electron transport in RTILs.

A novel Mg-MOF with unusual μ3-F dual-trinuclear cluster was successfully afforded by utilizing a solvent system of DMA/DMPU/HFP. Interestingly, as a luminescent thermometer, this MOF exhibits excellent low-temperature sensing capabilities.

A versatile luminescent Cl-decorated CPM-5 was successfully afforded by using a DMF/H2O/HCl solvent system. Interestingly, the highly stable CPM-5-Cl is suitable for application in Fe3+ sensing and as a blue LED and ratiometric thermometer.

Design of highly efficient heterojunctions for photocatalytic hydrogen evolution is of significant importance to address the energy shortage and environmental crisis. Nevertheless, the smart design of semiconductor-based heterojunctions at the atomic scale still remains a significant challenge hitherto. Herein, we report novel atomic CdS/ZnIn2S4 heterojunctions by in-situ epitaxially growing 2D ZnIn2S4 nanosheets onto the surface of 1D defective CdS nanorods. The strong electronic coupling between defective CdS and ZnIn2S4 is confirmed by transient photocurrent response measurements, •O2- and •OH radicals experiments, and PL results, leading to accelerated interfacial charge separation and transfer. Additionally, the elevated charge transfer and electronic coupling are further confirmed by theoretical calculations. Consequently, CdS/ZnIn2S4 hybrids exhibit superior photocatalytic hydrogen generation activity to pristine CdS. Our findings offer a new paradigm for designing atomic 1D/2D heterojunctions for efficient solar-driven energy conversion.

The relationship between depression and Alzheimer's disease (AD) is complex and still not well understood. We aimed to examine the roles of the AD core pathologies in modulating the associations of minimal depressive symptoms (MDSs) with cognitive impairments.A total of 721 participants who had measures of cognition, depressive symptoms, and cerebrospinal fluid AD biomarkers were included from the CABLE (Chinese Alzheimer's Biomarker and LifestylE) study. Causal mediation analyses with 10,000 bootstrapped iterations were conducted to explore the mediation effects of AD pathologies on cognition. The ADNI (Alzheimer's Disease Neuroimaging Initiative) was used 1) to replicate the mediation effects and 2) to examine the longitudinal relationships of MDSs with amyloid pathology and incident AD risk.In CABLE, MDSs were associated with poorer global cognition (p = .006) and higher amyloid burden as indicated by cerebrospinal fluid amyloid markers (p.0001). The influence of MDSs on cognition was partially mediated by amyloid pathology (a maximum of 85%). The mediation effects were replicated in 725 elderly persons without dementia (age, mean ± SD = 73.5 ± 6.9 years; 301 female subjects [42%]) in ADNI, such that the mediation percentage varied from 10% to 30% for general cognition, memory, and executive functions. Longitudinal analyses revealed a bidirectional relationship between MDSs and amyloid pathology (p = .01). MDSs were associated with 83% increased risk of developing AD dementia (hazard ratio = 1.83, p.01).Overall, amyloid pathology might partially mediate and magnify the influences of MDSs on cognitive impairments and AD risk.

By employing a tetraphenylethylene (TPE)-based tetracarboxylate linker, tetrakis(4-carboxyphenyl)ethylene (H4TCPE), we herein constructed a novel luminescent Mn-MOF based on a rare [Mn4(μ3-OH)2] cluster (SQNU-55). Interestingly, the TPE-based SQNU-55 not only provides a good material for the blue LED device, but also has a better luminescent molecular thermometer for low-temperature detection.

The coupling between electrons/holes from semiconductors and protons from electrolyte solutions at semiconductor/electrolyte interfaces is essential to semiconductor (photo)electrochemistry, that i...

It was unclear whether sex hormone-binding globulin (SHBG) was a circulating biomarker of Alzheimer’s disease (AD). We tested the cross-sectional relationships between plasma SHBG and cerebrospinal fluid (CSF) AD biomarkers in 707 non-demented adults. Next, the influences of plasma SHBG on dynamic changes of CSF Aβ42, hippocampus volume, brain metabolism, and cognition were explored in 448 non-demented adults from the Alzheimer’s disease Neuroimaging Initiative (ADNI). Finally, the predictive and diagnostic values of plasma SHBG in AD were explored. A positive correlation was found between SHBG levels in plasma and CSF. Individuals with higher plasma SHBG levels had lower CSF Aβ42 (p < 0.005), after adjusting for age, gender, education, APOE4 allele, and cognitive scores. Though no significant difference of plasma SHBG was observed between mild AD dementia and healthy normal, plasma SHBG could contribute to accelerated rates of CSF Aβ42 decrease (p < 0.0005), decline in brain metabolism (p < 0.05), and hippocampus atrophy (p < 0.01), cognitive decline (p < 0.01), as well as higher risk of AD dementia (p < 0.05). These findings indicated plasma SHBG could be a prodromal biomarker to predict disease progression in AD.

White matter hyperintensities (WMH) is mainly caused by cerebrovascular injury and may also increase the possibilities of progression to Alzheimer's disease. The present study aims to determine whether plasma neurofilament light (NFL) protein levels could predict the progression of WMH volume in elderly persons without dementia. The present study enrolled 1029 non-dementia participants from the Alzheimer's Disease Neuroimaging Initiative in which all had measurements of plasma NFL and WMH at baseline and 589 had longitudinal measurements during follow-up. Spearman correlation analyses and regression models were used to assess cross-sectional and longitudinal associations between plasma NFL and WMH. Plasma NFL concentration had a moderately strong correlation with WMH at baseline (r = 0.17, p < 0.001). Longitudinal analyses showed that higher baseline plasma NFL concentration was associated with accelerated progression of WMH (β=0.015, p = 0.007). Furthermore, higher change rates of plasma NFL could predict faster progression of WMH in the future (β=0.581, p = 0.002). The results of the study suggest that plasma NFL level might be used as a noninvasive biomarker to track variation trend in WMH in elderly persons without dementia.

Cognitive impairment is a debilitating manifestation in Parkinson’s disease (PD). We sought to investigate predictors of PD-CI (PD with cognitive impairment). We systematically searched PubMed and Cochrane Library for prospective cohort studies and pooled estimates via random-effects models. Primary analyses for all types of cognitive impairments and subgroup analyses by separate outcomes were conducted. A total of 28,009 studies were identified, of which 57 studies with 31 factors were included in the meta-analysis. In the primary analysis, 13 factors were associated with PD-CI, comprising advanced age [relative risk (RR) = 1.07, 95% confidence interval (CI) = 1.03–1.12], age at onset (RR = 4.43, 95% CI = 1.87–10.54), postural-instability-gait disorder (RR = 3.76, 95% CI = 1.36–10.40), higher Hoehn and Yahr stage (RR = 1.83, 95% CI = 1.35–2.47), higher UPDRS III score (RR = 1.04, 95% CI = 1.01–1.08), rapid eye movement sleep behavior disorder (RR = 3.72, 95% CI = 1.20–11.54), hallucinations (RR = 3.09, 95% CI = 1.61–5.93), orthostatic hypotension (RR = 2.98, 95% CI = 1.41–6.28), anxiety (RR = 2.59, 95% CI = 1.18–5.68), APOE e2 (RR = 6.47, 95% CI = 1.29–32.53), APOE e4 (RR = 3.04, 95% CI = 1.88–4.91), electroencephalogram theta power > median (RR = 2.93, 95% CI = 1.61–5.33), and alpha power

A case of human infection by H3N8 influenza virus

By employing a tetraphenylethylene (TPE)-based tetracarboxylate linker, tetrakis(4-carboxyphenyl)ethylene (H

A subgroup of overweight/obese individuals, who had favorable metabolic profiles, was termed as metabolically healthy overweight/obese (MHO). Several studies suggested that MHO individuals were not at increased risk of cardiovascular disease and all-course mortality. However, whether MHO is associated with excess risk of Alzheimer’s disease (AD) in elders remains unclear. To explore the risk of AD among MHO phenotype and investigate whether MHO associates with neurodegenerative biomarkers of AD, we assessed body mass index-metabolic status phenotypes of 1199 longitudinal elders from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort using the Adult Treatment Panel-III (ATP- III) criteria. MHO subjects were at a significantly decreased risk for AD (adjusted HR=0.73, 95% CI: 0.54-0.97) compared with metabolically healthy normal weight (MHNW) subjects. In multivariable linear regression models, the cross-sectional associations of MHO with cerebrospinal fluid (CSF) biomarkers, brain Aβ load, and cortical structure were explored. MHO was positively correlated with CSF-Aβ (β=0.746, P=0.015), hippocampal volume (β=0.181, P=0.011), and whole brain volume (β=0.133, P=0.004). The MHO phenotype of the elder conferred a decreased risk of AD and its role may be driven by Aβ.

Triggering receptor expressed on myeloid cells-1 (TREM1) has been reported to associate with Alzheimer’s disease (AD) pathology. Recently, TREM1 variant rs2234246A was reported to regulate TREM-1 protein and mRNA levels. We explored the effect of rs2234246 on AD specific biomarker (amyloid-β PET) to look into the role of this TREM1 locus in AD pathogenesis. We calculated the association of the TREM1 locus with amyloid deposition at baseline and follow-up using both multiple linear models and mixed effect models respectively in 522 the Alzheimer’s Disease Neuroimaging Initiative (ADNI) subjects. We also analyzed the association of TREM1 with this marker in subregions during the AD process. In the pooled sample, TREM1 rs2234246A was associated with the levels of mean standard uptake volume ratios (SUVRs) at baseline (p = 0.02) and the length of follow-up (p = 0.04) in the cross-sectional analysis and longitudinal study. Subgroup analyses showed no correlation between rs2234246A and amyloid deposition in the cognitively normal (CN) group. In the mild cognitive impairment (MCI) group, TREM1 rs2234246A reached significance at baseline (p = 0.04) and the length of follow-up (p = 0.04). In the AD group, TREM1 rs2234246A was associated with mean SUVR at baseline (p

Hippocampal atrophy rate has been correlated with cognitive decline and its genetic modifiers are still unclear. Here we firstly performed a genome-wide association study (GWAS) to identify genetic loci that regulate hippocampal atrophy rate. Six hundred and two non-Hispanic Caucasian elders without dementia were included from the Alzheimer's Disease Neuroimaging Initiative cohort. Three single nucleotide polymorphisms (SNPs) (rs4420638, rs56131196, rs157582) in the TOMM40-APOC1 region were associated with hippocampal atrophy rate at genome-wide significance and 3 additional SNPs (in TOMM40 and near MIR302F gene) reached a suggestive level of significance. Strong linkage disequilibrium between rs4420638 and rs56131196 was found. The minor allele of rs4420638 (G) and the minor allele of rs157582 (T) showed associations with lower Mini-mental State Examination score, higher Alzheimer Disease Assessment Scale-cognitive subscale 11 score and smaller entorhinal volume using both baseline and longitudinal measurements, as well as with accelerated cognitive decline. Moreover, rs56131196 (P = 1.96 × 10-454) and rs157582 (P = 9.70 × 10-434) were risk loci for Alzheimer's disease. Collectively, rs4420638, rs56131196 and rs157582 were found to be associated with hippocampal atrophy rate. Besides, they were also identified as genetic loci for cognitive decline.

Brain amyloid deposition is an early pathological event in Alzheimer’s disease (AD), and abnormally low levels amyloid-β42 peptide (Aβ42) in cerebrospinal fluid (CSF) can be detected in preclinical AD. To identify the genetic determinants that regulate the rate of CSF Aβ42 decline among non-demented elders, we conducted a genome-wide association study involved 321 non-demented elders from Alzheimer’s Disease Neuroimaging Initiative (ADNI) 1/GO/2 cohorts restricted to non-Hispanic Caucasians. A novel genome-wide significant association of higher annualized percent decline of CSF Aβ42 in the gene CBFA2T3 (CBFA2/RUNX1 translocation partner 3; rs13333659-T; p = 2.24 × 10−9) was identified. Besides displaying abnormal CSF Aβ42 levels, rs13333659-T carriers were more likely to exhibit a greater longitudinal cognitive decline (p = 0.029, β = 0.097) and hippocampal atrophy (p = 0.029, β = −0.160) in the non-demented elders, especially for the participants who were amyloid-positive at baseline. These findings suggest rs13333659 in CBFA2T3 as a risk locus to modulate the decline rate of CSF Aβ42 preceding the onset of clinical symptoms.

Tin oxide (SnO₂) based anode materials for lithium ion batteries (LIBs) have drawn much attention for their high theoretical capacity and energy density, but suffer from a large volume change and resulting a rapid capacity fading during charging/discharging cycles. To optimize the status, herein, SnO₂/carbon composites are synthesized using SnCl₄ · 5H₂O and glucose with different mass ratio as raw materials via a simple one-step hydrothermal process, following calcination under Ar gas atmosphere. As comparison, pure SnO₂ is synthesized as the same as SnO₂/carbon composites without glucose and calcination in air. The electrochemical impedance spectroscopy (EIS) measurements were used to investigate the lithium ions storage behavior in pure SnO₂ and the SnO₂@carbon composites. The EIS results indicate that pure SnO₂ has much larger electronic transfer resistance and smaller diffusion coefficient of Li+ resulting worst electrochemical performances, while carbon can substantially enhance the electronic conductivity of the composites and resulting better cycle stability and rate capability of the composite anodes. Moreover, the stability and capacity of the composites are different from each other due to diverse carbon content, surface area and particle size, in which, SnO₂-24%C exhibits better lithium storage performances. The initial discharge/charge capacities are up to 1650 and 890 mAh g-1 at the current density of 0.2 A g-1, and the reversible capacity even still maintains at 800 mAh g-1 after 60 cycles. The super electrochemical performances are attributed to that the proper content of carbon clusters as a support can buffer volume expansion of SnO₂ during cycling, enhance the electrode conductivity and accelerate the diffusion of Li+ ions in the composite. The results implying that the composite with proper carbon content has a wide application prospect for anode material of LIBs.

Nanostructure CuFe2O4/CuO composites are synthesized via a precipitation method with different surfactants mediated Prussian blue analogues (PBAs) as precursors and following calcination in air. Comparatively, P-CuFe2O4/CuO (synthesized with PVP) and graphene oxide (GO) are hydrothermal processed to obtain P-CuFe2O4/CuO/reduced-GO. The PBAs precursors present as small spherical particles with PVP (P-CuPB), irregular polygon blocks with SDBS (S-CuPB) and CTAB (C-CuPB). Porous CuFe2O4/CuO with different size are obtained after calcining the PBAs and employed as anode of lithium ion batteries. The P-CuFe2O4/CuO exhibits an excellent capacity of 630.5 mAh g−1 with coulombic efficiency (CE) above 97%, which are better than the other two samples, and P-CuFe2O4/CuO/R-GO shows further improved reversible and stable capacity of 720 mAh g−1 with CE above 99% cycled at 500 mA g−1 even after 300 times. The results imply that surfactants can influence the particle structure and lithium storage performance. Besides, R-GO can effectively increase lithium ions insertion/de-insertion kinetics by supplying the matrix and buffer cushion for metal oxide volume changing during cycling.

Age-related hearing loss (ARHL) has been considered as a promising modifiable risk factor for cognitive impairment and dementia. Nonetheless, it is still unclear whether age-related hearing loss associates with neurodegenerative biomarkers of Alzheimer’s disease (AD). Participants with ARHL were selected from the established Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. In multivariable models, the cross-sectional and longitudinal associations of ARHL with CSF β-amyloid (Aβ) and tau measurements, brain Aβ load, and cortical structural measures were explored. ARHL was associated with higher CSF levels of tau (p < 0.001) or ptau181 (p < 0.05) at baseline as well as faster elevation rates of these two types of biomarkers (p < 0.05). Although the baseline volume/thickness of hippocampus (p < 0.05) and entorhinal cortex (p < 0.0005) were higher in individuals with ARHL, these two regions (p < 0.01 for hippocampus, p < 0.05 for entorhinal cortex) displayed significantly accelerated atrophy in individuals with ARHL. No association of ARHL with CSF or brain Aβ levels was found. Subgroup analyses indicated that the above effects of ARHL were more significant in non-demented stage. Age-related hearing loss was associated with elevated cerebrospinal fluid tau levels and atrophy of entorhinal cortex.

Background The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism emerged as a risk factor for Alzheimer's disease (AD). However, little was known about its effects on the process of potential AD. Objective To explore the effects of the Val66Met polymorphism on cognition, cerebrospinal fluid (CSF), and neuroimaging markers in non-demented elderly individuals. Methods A total of 1,081 adults without dementia (375 healthy subjects and 706 individuals with mild cognitive impairment) were recruited from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to test the influence of BDNF Val66Met polymorphism on cognitive impairment, brain structure atrophy, and change in the levels of CSF biomarkers. Moreover, we also conducted our study in abnormal amyloid-β (A+) subgroup and normal amyloid-β (A-) subgroup, as well as in APOEɛ4 carriers and non-carriers. Results The BDNF Val66Met polymorphism had significant association with atrophy of the entorhinal cortex and Mini-Mental State Examination (MMSE) scores in the non-demented elderly and A + subgroup, while no association was found in A-subgroup. What is more, there was a significant effect of interaction between BDNF Val66Met and amyloid-β load in MMSE. In addition, significant associations of BDNF Val66Met with the entorhinal cortex and ventricular volumes were found among APOEɛ4 non-carriers, but not APOEɛ4 carriers. Conclusions The BDNF Val66Met polymorphism is associated with cognitive impairment and brain atrophy among the non-demented elderly, APOEɛ4 non-carriers and A + subgroup, implying the potential of the Val66Met polymorphism as an important genetic factor for AD-related neurodegeneration.

Poly(vinylidenefluoride-co-hexafluoropropylene) (P(VDF-HFP))/Li1.3Al0.3Ti1.7(PO4)3 (LATP)/P(VDF-HFP) sandwiched hybrid solid electrolytes were precisely tailored and successfully fabricated to assemble into all-solid-state lithium-ion batteries, which were systematically evaluated on microstructure, morphology, thermal stability and electrochemical performance. The sandwiched hybrid solid electrolytes can achieve intimate contact with cathode and anode electrodes to present an excellent interfacial stability. Furthermore, the sandwiched hybrid solid electrolytes possess flexible surface, wide electrochemical working window of 4.7 V, high ionic conductivity of 0.763 mS·cm−1 and high thermal stability of 460 °C, which may contribute to realizing the practical application in all-solid-state lithium-ion batteries. The assembled cells with the hybrid solid electrolytes can quickly stabilize at a specific discharge capacity of 145.4 mAh·g−1 at 0.1C after only 5 cycles and present admirable rate performance. In addition, morphology characterizations of the sandwiched hybrid solid electrolytes after long-term cycles show a relatively integrated structure coating with a compact LATP layer. The investigations afford a promising strategy that the sandwiched hybrid solid electrolytes can overcome the mechanical limitations of the interface between electrodes and inorganic solid electrolytes to provide favorable properties for all-solid-state lithium-ion batteries.

BackgroundSex-related difference in Alzheimer’s disease (AD) has been proposed, and apolipoprotein E (ApoE) isoforms have been suggested to be involved in the pathogenesis of AD.ObjectiveWe aimed to explore whether cerebrospinal fluid (CSF) ApoE is associated with AD biomarkers and whether the associations are different (between sexes).MethodsData of 309 participants [92 with normal cognition, 148 with mild cognitive impairment (MCI), and 69 with AD dementia] from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) were cross-sectionally evaluated with the multiple linear regression model and longitudinally with the multivariate linear mixed-effects model for the associations of CSF ApoE with AD biomarkers. Sex–ApoE interaction was used to estimate whether sex moderates the associations of CSF ApoE and AD biomarkers.ResultsSignificant interactions between CSF ApoE and sex on AD biomarkers were observed [amyloid-β (Aβ):p= 0.0169 and phosphorylated-tau (p-tau):p= 0.0453]. In women, baseline CSF ApoE levels were significantly associated with baseline Aβ (p= 0.0135) and total-tau (t-tau) (p< 0.0001) as well as longitudinal changes of the biomarkers (Aβ:p= 0.0104; t-tau:p= 0.0110). In men, baseline CSF ApoE levels were only correlated with baseline p-tau (p< 0.0001) and t-tau (p< 0.0001) and did not aggravate AD biomarkers longitudinally.ConclusionThe associations between CSF ApoE and AD biomarkers were sex-specific. Elevated CSF ApoE was associated with longitudinal changes of AD biomarkers in women, which indicates that CSF ApoE might be involved in the pathogenesis of AD pathology in a sex-specific way.

The microtubule-associated protein tau gene (MAPT) rs242557 variant is associated with multiple tauopathies and dementia. This study investigated whether it was correlated with brain tau-PET uptake in non-demented elders. Ninety non-demented elders were identified from the Alzheimer's Disease Neuroimaging Initiative cohort. We compared standardized uptake value ratios (SUVRs) of tau-PET tracer 18F-AV-1451 between rs242557 variant carriers and non-carriers in 25 regions of interest (ROIs). The minor allele A was associated with increased hippocampus 18F-AV-1451 uptake in non-demented elders (left: β = 0.111, Bonferroni corrected p = 0.035; right: β = 0.103, Bonferroni corrected p = 0.031). Aβ-positive participants (left: β = 0.206, Bonferroni corrected p = 0.029; right: β = 0.198, Bonferroni corrected p = 0.035) and APOE e4 non-carriers (left: β = 0.140, Bonferroni corrected p = 0.006; right: β = 0.134, Bonferroni corrected p = 0.004) exhibited approximately the same findings in hippocampus. Considering no obvious associations in other regions, we confirmed the significant correlation of MAPT rs242557 risk variant with increased hippocampus tau deposition in non-demented elders. With higher magnitude signals in the hippocampus that is more likely to be uniquely affected in AD, the tau PET ligand 18F-AV-1451 seemed to possess a specific binding property for AD-like tau pathology.

Summary Photocatalysis has offered a promising opportunity for selective transformation of biomass to high-value chemicals or fuels under mild conditions. Whereas titanium oxide has been widely used for photocatalytic pollutant degradation, H2 evolution, and CO2 reduction, few studies have been devoted to TiO2-based photocatalytic valorization of biomass or biomass-derived platform compounds. Here, we report on surface-controlled photocatalysis of TiO2 for selective valorization of furfurals and vanillin that are lignocellulose-derived key platform compounds. The reaction can be switched from hydrogenation of aldehyde group to C–C coupling by manipulating exposed facets; furanic and aromatic alcohols or coupling products, which are fine chemicals or jet-fuel precursors, could be produced with high selectivity. Our studies elucidate that the facet-dependent density of oxygen vacancies governs the charge distribution and adsorption strength of surface species and thus controls product selectivity. The present work offers an example of selectivity control by engineering TiO2 surfaces for valorization of biomass-derived feedstocks.

Background: Evidence on preventing Alzheimer's disease (AD) is challenging to interpret due to varying study designs with heterogeneous endpoints and credibility. We completed a systematic review and meta-analysis of current evidence with prospective designs to propose clinical recommendations on AD prevention. Methods: Electronic databases and relevant websites were searched from inception to March 1, 2019. Both observational prospective studies (OPSs) and randomized controlled trials (RCTs) were included. The multivariable-adjusted effect estimates were pooled by random-effects models, with credibility assessment according to its risk of bias, inconsistency, and imprecision. Levels of evidence and classes of recommendations were summarized. Findings: A total of 44,676 reports were identified, and 243 OPSs and 153 RCTs were eligible for analysis after exclusion based on pre-decided criteria, among which 104 modifiable factors and 11 interventions were included for the meta-analyses. In the OPSs, 26 risk factors and 8 protective factors were found to significantly modify AD risk by an effect size of over 25%, amongst which eight factors were rated at a moderate-to-high level of evidence. Among the interventions tested in RCTs, physical exercise and the homocysteine lowering treatment were the most promising interventions to reduce AD risk. Finally, 21 recommendations are proposed based on the consolidated evidence, with 'Class I' recommendations targeting 19 factors: ten are with 'Level A' strong evidence (cognitive activity, hyperhomocysteinemia, high BMI in late-life, depression, stress, diabetes, head trauma, hypertension in midlife, orthostatic hypotension, and education) and nine with 'Level B' weaker evidence (obesity in midlife, weight loss in late-life, physical exercise, smoking, sleep, CVD, frailty, atrial fibrillation, and Vitamin C). In contrast, two interventions are not recommended: estrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B). Interpretation: Our study mapped the current evidence profile and assessed the findings in order to guide future research directions for AD prevention. Evidence-based recommendations are proposed, offering clinicians and stakeholders current guidance for the prevention of AD. Funding Statement: The authors stated: "There was no direct funding source for this study." Declaration of Interest: JTY serves as an associate editor-in-chief for Annals of Translational Medicine, is senior editor for Journal of Alzheimer's Disease. SA has received grants from Europe, Ipsen, and France Alzheimer, served as a consultant for Ipsen, Pierre Fabre, Lilly, Nestle, Sanof, and Servier, and received non-financial support from Biogen, Nutrition Sante, Pfzer, and Icon, and other support from the AMPA Association. SG has received clinical trial support from Lilly and Roche in DIAN-TU, TauRx Therapeutics (TauRx), and Lundbeck; has been a data safety monitoring board (DSMB) member of ADCS, ATRI, API, and Eisai; and has been a scientific adviser to Affiris, BoehringerIngelheim, Lilly, Roche, Servier, Sanofi, Schwabe, Takeda, and TauRx. PSA has received grants from the US Alzheimer’s Association, Janssen, Lilly, the US National Institute on Aging, and Toyama; and consulting fees from Abbott, Abbvie, Amgen, Anavex, AstraZeneca, Biogen Idec, Biotie, Bristol-Myers Squibb, Cardeus, Cohbar, Eisai, Elan, Eli Lilly, Genentech, Ichor, iPerian, Janssen, Lundbeck, Medivation, Merck, NeuroPhage, Novartis, Pfizer, Probiodrug, Roche, Somaxon, and Toyama, outside the submitted work. BV reports grants from Pierre Fabre, Avid, Exonhit, AbbVie, Lilly, Lundbeck, MSD, Otsuka, Regenron, Sanof, Roche, AstraZeneca, LPG Systems, Nestle, and Alzheon, and personal fees from Lilly, Lundbeck, MSD, Otsuka, Roche, Sanof, Biogen, Nestle, Transition Therapeutics, and Takeda. All other authors declare no competing interests. Ethics Approval Statement: The authors followed the recommendations by the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2009 guidelines.

Progranulin (PGRN) is a secreted pleiotropic glycoprotein associated with the development of common neurodegenerative diseases. Understanding the pathophysiological role of PGRN may help uncover biological underpinnings. We performed a genome-wide association study to determine the genetic regulators of cerebrospinal fluid (CSF) PGRN levels. Common variants in region of FAM171A2 were associated with lower CSF PGRN levels (rs708384, P = 3.95 × 10−12). This was replicated in another independent cohort. The rs708384 was associated with increased risk of Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia and could modify the expression of the FAM171A2 gene. FAM171A2 was considerably expressed in the vascular endothelium and microglia, which are rich in PGRN. The in vitro study further confirmed that the rs708384 mutation up-regulated the expression of FAM171A2, which caused a decrease in the PGRN level. Collectively, genetic, molecular, and bioinformatic findings suggested that FAM171A2 is a key player in regulating PGRN production.

OBJECTIVE: To study the value of quantitative electroencephalography (qEEG) in evaluating the effect of blood glucose on the brain function of preterm infants. METHODS: The preterm infants who were admitted to the Department of Neonatology, The Third Xiangya Hospital of Central South University, from January to December 2019 were enrolled. According to the level of blood glucose, they were divided into group 1 (blood glucose < 4.95 mmol/L), group 2 (blood glucose 4.95 to < 6.60 mmol/L), group 3 (blood glucose 6.60 to < 8.55 mmol/L), and group 4 (blood glucose ≥ 8.55 mmol/L). The changes in qEEG parameters were compared between groups, and a correlation analysis was performed for blood glucose and qEEG parameters. RESULTS: A total of 39 preterm infants were enrolled (84 blood glucose measurements). Compared with group 4, the other three groups had significant increases in the total spectral power of each brain region and the absolute power of each frequency band in the frontal and occipital regions (P < 0.05). The total spectral power, δ/θ ratio, and (δ + θ)/(α + β) ratio of each brain region were negatively correlated with blood glucose level, while the relative power of θ frequency band was positively correlated with blood glucose level (P < 0.05). CONCLUSIONS: With the change in blood glucose, there are significant changes in the total spectral power of each brain region, the power of each frequency band, and the frequency spectrum composition on qEEG in preterm infants. qEEG may therefore become an important tool to monitor the effect of abnormal blood glucose on brain function in preterm infants.

Introduction Amyloid beta (Aβ) deposition was identified to precede tau pathology and neurodegeneration in familial Alzheimer's disease (AD). But the divergence between sporadic and familial AD limits the extension of these findings to sporadic AD. Methods Longitudinal changes of biomarkers among different stages were assessed using linear mixed‐effects models. The slopes of the models were used to estimate rates of change to calculate the biomarker trajectories in sporadic AD. Results Cerebrospinal fluid (CSF) Aβ was estimated to decline 45.2 years (abnormal: 27.8 years) before dementia, and Aβ deposition seemed to increase 31.7 years (abnormal: 26.7 years) before dementia. It was estimated to take 29.0 years (CSF t‐tau), 12.2 years (memory), 11.6 years (hippocampus), 9.3 years (hypometabolism), and 6.1 years (cognition) to move from normal to dementia. Discussion The trajectory in sporadic AD is led by Aβ accumulation, followed by CSF t‐tau increase, memory deficits, brain atrophy, hypometabolism, and cognitive decline.