Epstein-Barr virus infection with non-tumor-associated Anti-N-Methyl-D-Aspartate receptor encephalitis: a case report and review of literature.

To study a case of a middle-aged male with a non-tumor-associated Epstein-Barr virus (EBV) infection associated with Anti-N-methyl-D-aspartate receptor encephalitis (NMDARE), to explore the role of EBV in the pathogenesis of anti-NMDARE. The patient was diagnosed with "Anti-NMDARE, EBV infection" by using Cerebrospinal fluid (CSF) autoimmune encephalitis profile, and Metagenomics Next-Generation Sequencing (mNGS) pathogenic microbial assays, we discuss the relationship between EBV and NMDARE by reviewed literature. EBV infection may trigger and enhance anti-NMDARE, and the higher the titer of NMDAR antibody, the more severe the clinical presentation.

Water effect on the band edges of anatase TiO2 surfaces: A theoretical study on charge migration across surface heterojunctions and facet-dependent photoactivity.

The charge migration mechanism across the surface heterojunction constructed on an anatase TiO2 nanocrystal is still under debate. To solve this longstanding question, we present a systematic study of the band edges (vs. standard hydrogen electrode, SHE) of aqueous TiO2 interfaces with anatase (101), (100) and (001) surfaces, using a combination of density functional theory-based molecular dynamics (DFTMD) and efficient computational SHE (cSHE) methods. Our calculations show that the conduction band minimum (CBM) of the (101) surface is lower than that of (001) and (100) surfaces, which is thermodynamically favorable for electrons migrating to the (101) surface through the surface heterojunction, while the hole preferentially accumulates on the (100) surface due to its highest valence band minimum (VBM). In addition, we qualitatively explore the facet-dependent photocatalytic activity of anatase TiO2. Due to the possession of both the beneficial atomic structure (with 100% undercoordinated Ti5c atoms at the surface) and electronic structure (more strongly oxidizing holes in the VBM and efficient electron-hole spatial separation separation), the (001) surface exhibits the most efficient photocatalytic performance for water oxidation. Furthermore, it is confirmed that the use of simplified theoretical models neglecting the detailed atomic structures of water at the aqueous interface is inadequate to predict the band alignment of semiconductors relative to water redox potentials, so that it may result in substantial errors in evaluating the photocatalytic performance of materials to be used for water splitting.

Visualizing an Electrochemically Induced Radical Cation of Bipyridine at Au(111)/Ionic Liquid Interfaces toward a Single-Molecule Switch.

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.

Evidence-based prevention of Alzheimer's disease: systematic review and meta-analysis of 243 observational prospective studies and 153 randomised controlled trials.

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 evidence-based suggestions on AD prevention. METHODS: Electronic databases and relevant websites were searched from inception to 1 March 2019. Both observational prospective studies (OPSs) and randomised 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 suggestions were summarised. RESULTS: 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, from which 104 modifiable factors and 11 interventions were included in the meta-analyses. Twenty-one suggestions are proposed based on the consolidated evidence, with Class I suggestions targeting 19 factors: 10 with Level A strong evidence (education, cognitive activity, high body mass index in latelife, hyperhomocysteinaemia, depression, stress, diabetes, head trauma, hypertension in midlife and orthostatic hypotension) and 9 with Level B weaker evidence (obesity in midlife, weight loss in late life, physical exercise, smoking, sleep, cerebrovascular disease, frailty, atrial fibrillation and vitamin C). In contrast, two interventions are not recommended: oestrogen replacement therapy (Level A2) and acetylcholinesterase inhibitors (Level B). INTERPRETATION: Evidence-based suggestions are proposed, offering clinicians and stakeholders current guidance for the prevention of AD.

[Effect of blood glucose on quantitative electroencephalography parameters in preterm infants].

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+ß) 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.

[Clinical features of children with SARS-CoV-2 infection: an analysis of 13 cases from Changsha, China].

OBJECTIVE: To study the clinical features of children with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: A retrospective analysis was performed for the clinical data of 13 children with SARS-CoV-2 infection who hospitalized in a Changsha hospital. RESULTS: All 13 children had the disease onset due to family aggregation. Of the 13 children, 2 had no symptoms, and the other 11 children had the clinical manifestations of fever, cough, pharyngeal discomfort, abdominal pain, diarrhea, convulsions, or vomiting. As for clinical typing, 7 had mild type, 5 had common type, and 1 had severe type. The median duration of fever was 2 days in 6 children. All 13 children had normal levels of peripheral blood lymphocyte counts, immunoglobulins, CD4, CD8, and interleukin-6. The median time to clearance of SARS-CoV-2 was 13 days in the nasopharyngeal swabs of the 13 children. Three children presented false negatives for RT-PCR of SARS-CoV-2. SARS-CoV-2 RNA remained detectable in stools for 12 days after the nasopharyngeal swab test yielded a negative result. Abnormal CT findings were observed in 6 children. All 13 children were cured and discharged and they were normal at 2 weeks after discharge. CONCLUSIONS: Intra-family contact is the main transmission route of SARS-CoV-2 infection in children, and there is also a possibility of fecal-oral transmission. Mild and common types are the major clinical types in children with SARS-CoV-2 infection, and cytokine storm is not observed. Children with SARS-CoV-2 infection tend to have a good short-term prognosis, and follow-up is needed to observe their long-term prognosis. Multiple nucleic acid tests should be performed for patients with SARS-CoV-2 infection and their close contacts by multiple site sampling.

Discovery of susceptibility loci associated with tuberculosis in Han Chinese.

Genome-wide association studies (GWASs) have revealed the worldwide heterogeneity of genetic factors in tuberculosis (TB) susceptibility. Despite having the third highest global TB burden, no TB-related GWAS has been performed in China. Here, we performed the first three-stage GWAS on TB in the Han Chinese population. In the stage 1 (discovery stage), after quality control, 691 388 SNPs present in 972 TB patients and 1537 controls were retained. After replication on an additional 3460 TB patients and 4862 controls (stages 2 and 3), we identified three significant loci associated with TB, the most significant of which was rs4240897 (logistic regression P = 1.41 × 10-11, odds ratio = 0.79). The aforementioned three SNPs were harbored by MFN2, RGS12 and human leukocyte antigen class II beta chain paralogue encoding genes, all of which are candidate immune genes associated with TB. Our findings provide new insight into the genetic background of TB in the Han Chinese population.

Modifiable risk factors for cognitive impairment in Parkinson's disease: A systematic review and meta-analysis of prospective cohort studies.

BACKGROUND: Cognitive impairment is a common and devastating manifestation in Parkinson's disease (PD). We aimed to identify modifiable risk factors for PD with cognitive impairment. METHODS: We systematically searched PubMed and the Cochrane Library from June 1937 to September 2018 and included prospective cohort studies with random-effects model used to combine estimates. Primary analyses for all types of cognitive impairments and subgroup analyses for separate outcomes were conducted. RESULTS: A total of 31,298 articles were identified, of which 32 articles with 18 factors met the inclusion criteria for meta-analysis. In the primary analysis, 9 modifiable risk factors were found to increase the risk of PD with cognitive impairment, including postural-instability-gait disorder (relative risk = 3.76, 95% confidence interval = 1.36-10.40), hallucinations (relative risk = 3.09, 95% confidence interval = 1.61-5.93), orthostatic hypotension (relative risk = 2.98, 95% confidence interval = 1.41-6.28), cerebrovascular disease (relative risk = 1.52, 95% confidence interval = 1.01-2.28), diabetes mellitus (relative risk = 1.47, 95% confidence interval = 1.13-1.92), obesity (relative risk = 1.38, 95% confidence interval = 1.15-1.65), cardiac disease (relative risk = 1.35, 95% confidence interval = 1.17-1.56), alcohol consumption (relative risk = 1.32, 95% confidence interval = 1.15-1.52), and smoking (relative risk = 1.31, 95% confidence interval = 1.14-1.50). In the subgroup analysis, postural-instability-gait disorder subtype, orthostatic hypotension and hallucinations may increase the risk of dementia in PD. A total of 37 articles were included in the systematic review, in which 9 risk factors and 1 protective factor were additionally associated in single studies with the risk of PD with cognitive impairment, and 5 factors were associated with specific cognition domains. CONCLUSIONS: Effective interventions in the management of PD symptoms, comorbidities, and lifestyles may be promising to reduce PD with cognitive impairment risk. © 2019 International Parkinson and Movement Disorder Society.

One-Step Hydrothermal Synthesis of SnO2@Carbon Composites with Super Lithium Ions Storage Performances.

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.

Frequency and longitudinal clinical outcomes of Alzheimer's AT(N) biomarker profiles: A longitudinal study.

INTRODUCTION: We aimed to estimate the frequency of each AT(N) (ß-amyloid deposition [A], pathologic tau [T], and neurodegeneration [N]) profile in different clinical diagnosis groups and to describe the longitudinal change in clinical outcomes of individuals in each group. METHODS: Longitudinal change in clinical outcomes and conversion risk of AT(N) profiles are assessed using linear mixed-effects models and multivariate Cox proportional-hazard models, respectively. RESULTS: Participants with A+T+N+ showed faster clinical progression than those with A-T-N- and A+T±N-. Compared with A-T-N-, participants with A+T+N± had an increased risk of conversion from cognitively normal (CN) to incident prodromal stage of Alzheimer's disease (AD), and from MCI to AD dementia. A+T+N+ showed an increased conversion risk when compared with A+T±N-. DISCUSSION: The 2018 research framework may provide prognostic information of clinical change and progression. It may also be useful for targeted recruitment of participants with AD into clinical trials.

Utility of Novel Plasma Metabolic Markers in the Diagnosis of Pediatric Tuberculosis: A Classification and Regression Tree Analysis Approach.

Although tuberculosis (TB) has been the greatest killer due to a single infectious disease, pediatric TB is still hard to diagnose because of the lack of sensitive biomarkers. Metabolomics is increasingly being applied in infectious diseases. But little is known regarding metabolic biomarkers in children with TB. A combination of a NMR-based plasma metabolic method and classification and regression tree (CART) analysis was used to provide a broader range of applications in TB diagnosis in our study. Plasma samples obtained from 28 active TB children and 37 non-TB controls (including 21 RTIs and 16 healthy children) were analyzed by an orthogonal partial least-squares discriminant analysis (OPLS-DA) model, and 17 metabolites were identified that can separate children with TB from non-TB controls. CART analysis was then used to choose 3 of the markers, l-valine, pyruvic acid, and betaine, with the least error. The sensitivity, specificity, and area under the curve (AUC) of the 3 metabolites is 85.7% (24/28, 95% CI, 66.4%, 95.3%), 94.6% (35/37, 95% CI, 80.5%, 99.1%), and 0.984(95% CI, 0.917, 1.000), respectively. The 3 metabolites demonstrated sensitivity of 82.4% (14/17, 95% CI, 55.8%, 95.3%) and specificity of 83.9% (26/31, 95% CI, 65.5%, 93.9%), respectively, in 48 blinded subjects in an independent cohort. Taken together, the novel plasma metabolites are potentially useful for diagnosis of pediatric TB and would provide insights into the disease mechanism.

Compensatory Mutations of Rifampin Resistance Are Associated with Transmission of Multidrug-Resistant Mycobacterium tuberculosis Beijing Genotype Strains in China.

Mycobacterium tuberculosis can acquire resistance to rifampin (RIF) through mutations in the rpoB gene. This is usually accompanied by a fitness cost, which, however, can be mitigated by secondary mutations in the rpoA or rpoC gene. This study aimed to identify rpoA and rpoC mutations in clinical M. tuberculosis isolates in northern China in order to clarify their role in the transmission of drug-resistant tuberculosis (TB). The study collection included 332 RIF-resistant and 178 RIF-susceptible isolates. The majority of isolates belonged to the Beijing genotype (95.3%, 486/510 isolates), and no mutation was found in rpoA or rpoC of the non-Beijing genotype strains. Among the Beijing genotype strains, 27.8% (89/320) of RIF-resistant isolates harbored nonsynonymous mutations in the rpoA (n = 6) or rpoC (n = 83) gene. The proportion of rpoC mutations was significantly higher in new cases (P = 0.023) and in strains with the rpoB S531L mutation (P < 0.001). In addition, multidrug-resistant (MDR) strains with rpoC mutations were significantly associated with 24-locus mycobacterial interspersed repetitive-unit-variable-number tandem-repeat clustering (P = 0.016). In summary, we believe that these findings indirectly suggest an epistatic interaction of particular mutations related to RIF resistance and strain fitness and, consequently, the role of such mutations in the spread of MDR M. tuberculosis strains.

Prevalence and molecular characteristics of drug-resistant Mycobacterium tuberculosis in Beijing, China: 2006 versus 2012.

BACKGROUND: As the epidemic of MDR-TB and XDR-TB becomes increasingly severe, it is important to determine the clinical characteristics and molecular epidemiology of MDR-TB and XDR-TB. Recently, many studies have shown that clinical features and molecular characteristics of drug-resistant strains vary in different geographical areas, however, further information is needed to assess the dynamic evolution of drug-resistant TB. Comparative studies between different time periods are necessary to elucidate the development of drug-resistant TB. RESULTS: A total of 255 and 537 strains were collected from Beijing Chest Hospital in 2006 and in 2012, respectively. Drug-resistance rates and mutations associated with resistance to first-line anti-tuberculosis (TB) drugs were compared. The overall rate of drug resistance among strains of TB in 2012 was 54.4 %, significantly higher than that in 2006 (34.9 %, P < 0.001). Rates of resistance to each first-line drug (isoniazid, rifampicin, streptomycin and ethambutol) and to second-line drug ofloxacin increased significantly from 2006 to 2012. The overall MDR rate also increased significantly from 2006 (14.9 %) to 2012 (27.0 %). The rate of MDR increased significantly between these two time periods in previously treated cases (P = 0.023) but not in new cases (P = 0.073), and the rate of XDR was similar in new cases at the two time periods, but was marginally higher in 2012 in previously treated cases (P = 0.056). Previous treatment was found to be a risk factor for drug-resistant TB, especially for MDR-TB. In addition, the proportion of drug resistant isolates in which katG, the mabA-inhA promoter, oxyR-ahpC intergenic region, rpoB, rpsL, and embB were mutated was similar in 2006 and 2012, however patterns of mutation in these loci were more diverse in 2012 compared to 2006. CONCLUSIONS: Our data suggests that the prevalence of drug resistant TB remains high in Beijing, China, and that increasing rates of resistance in M. tuberculosis to all anti-TB drugs should be considered when choosing an optimal anti-TB regimen. Moreover, acquired multi-drug resistance may play a primary role in the MDR-TB epidemic in Beijing, China. Consequently, this highlights the importance of an earlier start to effective and supervised treatment in order to reduce the burden of retreatment.

Risk factors for predicting progression from mild cognitive impairment to Alzheimer's disease: a systematic review and meta-analysis of cohort studies.

OBJECTIVE: We sought to identify the risk factors for predicting the progression from mild cognitive impairment (MCI) to Alzheimer's disease (AD). METHODS: We searched 6 electronic databases for cohort studies published from January 1966 to March 2015. Eligible studies were required to be relevant to the subject and provide sufficient data for our needs. RESULTS: 60 cohort studies with 14,821 participants from 16 countries were included in the meta-analysis. The strongest positive associations between risk factors and the progression from MCI to AD were found for abnormal cerebrospinal fluid (CSF), phosphorylated τ (p-τ) (relative risk (RR)=2.43, 95% CI=1.70 to 3.48), abnormal CSF τ/Aß1-42 (RR=3.77, 95% CI=2.34 to 6.09), hippocampal atrophy (RR=2.59, 95% CI=1.95 to 3.44), medial temporal lobe atrophy (RR=2.11, 95% CI=1.70 to 2.63) and entorhinal atrophy (RR=2.03, 95% CI=1.57 to 2.62). Further positive associations were found for the presence of apolipoprotein E (APOE)ε4ε4 and at least 1 APOEε4 allele, CSF total-τ (t-τ), white matter hyperintensity volume, depression, diabetes, hypertension, older age, female gender, lower mini-mental state examination (MMSE) score and higher AD assessment scale cognitive subscale (ADAS-cog) score. Negative associations were found for high body mass index (RR=0.85, 95% CI=0.76 to 0.96) and higher auditory verbal learning test delay score (RR=0.86, 95% CI=0.77 to 0.96). CONCLUSIONS: Patients with MCI with APOEε4, abnormal CSF τ level, hippocampal and medial temporal lobe atrophy, entorhinal atrophy, depression, diabetes, hypertension, older age, female gender, lower MMSE score and higher ADAS-cog score, had a high risk for the progression to AD.

Meta-analysis of modifiable risk factors for Alzheimer's disease.

BACKGROUND: The aetiology of Alzheimer's disease (AD) is believed to involve environmental exposure and genetic susceptibility. The aim of our present systematic review and meta-analysis was to roundly evaluate the association between AD and its modifiable risk factors. METHODS: We systematically searched PubMed and the Cochrane Database of Systematic Reviews from inception to July 2014, and the references of retrieved relevant articles. We included prospective cohort studies and retrospective case-control studies. RESULTS: 16,906 articles were identified of which 323 with 93 factors met the inclusion criteria for meta-analysis. Among factors with relatively strong evidence (pooled population >5000) in our meta-analysis, we found grade I evidence for 4 medical exposures (oestrogen, statin, antihypertensive medications and non-steroidal anti-inflammatory drugs therapy) as well as 4 dietary exposures (folate, vitamin E/C and coffee) as protective factors of AD. We found grade I evidence showing that one biochemical exposure (hyperhomocysteine) and one psychological condition (depression) significantly increase risk of developing AD. We also found grade I evidence indicative of complex roles of pre-existing disease (frailty, carotid atherosclerosis, hypertension, low diastolic blood pressure, type 2 diabetes mellitus (Asian population) increasing risk whereas history of arthritis, heart disease, metabolic syndrome and cancer decreasing risk) and lifestyle (low education, high body mass index (BMI) in mid-life and low BMI increasing the risk whereas cognitive activity, current smoking (Western population), light-to-moderate drinking, stress, high BMI in late-life decreasing the risk) in influencing AD risk. We identified no evidence suggestive of significant association with occupational exposures. CONCLUSIONS: Effective interventions in diet, medications, biochemical exposures, psychological condition, pre-existing disease and lifestyle may decrease new incidence of AD.

Disease trajectories in older adults with non-AD pathologic change and comparison with Alzheimer's disease pathophysiology: A longitudinal study.

Based on the 'AT(N)' system, individuals with normal amyloid biomarkers but abnormal tauopathy or neurodegeneration biomarkers are classified as non-Alzheimer's disease (AD) pathologic change. This study aimed to assess the long-term clinical and cognitive trajectories of individuals with non-AD pathologic change among older adults without dementia, comparing them to those with normal AD biomarkers and AD pathophysiology. Analyzing Alzheimer's Disease Neuroimaging Initiative data, we evaluated clinical outcomes and conversion risk longitudinally using mixed effects models and multivariate Cox proportional hazard models. We found that compared to individuals with A-T-N-, those with abnormal tauopathy or neurodegeneration biomarkers (A-T + N-, A-T-N + , and A-T + N + ) had a faster rate of cognitive decline and disease progression. Individuals with A-T + N + had a faster rate of decline than those with A-T + N-. Additionally, in individuals with the same baseline tauopathy and neurodegeneration biomarker status, the presence of baseline amyloid could accelerate cognitive decline and clinical progression. These findings provide a foundation for future studies on non-AD pathologic change and its comparison with AD pathophysiology.

Associations Between TREML2 Gene Variants and Alzheimer's Disease: Biomarkers, Neuroimage, and Cognition.

BACKGROUND: Recent genetic research identified a protective factor against late-onset Alzheimer's disease (AD) in Caucasians, a variant called rs3747742-C in the TREML2 gene. However, the roles of other TREML2 variants in AD have not been fully explored. OBJECTIVE: We conducted a focused analysis of 16 TREML2 variants, examining their connection to AD by studying their correlation with cerebrospinal fluid (CSF) proteins, neuroimage, and cognition in the Alzheimer's Disease Neuroimaging Initiative database (ADNI). METHODS: A multiple linear regression model was utilized to estimate potential associations between TREML2 genotypes and various endophenotypes in the entire ADNI sample at baseline, with age, gender, years of education, and APOE ɛ4 status included as covariates. To examine changes in clinical outcomes over time, linear mixed-effects models were employed. RESULTS: We found that the SNP rs17328707-A was associated with higher ADNI-VS scores, smaller ventricles, and larger middle temporal volume at baseline. The SNP rs6915083-G was linked to lower CSF t-tau and p-tau levels, and higher CSF Aß levels. The SNP rs9394766-G was associated with a smaller hippocampus and larger ventricles at baseline. In longitudinal cohorts, the rs6915083-G SNP was associated with changes in ADNI-MEM and ADNI-EF scores, as well as the rate of hippocampal and middle temporal atrophy. CONCLUSION: Our findings reveal that TREML2 gene variants have different effects on AD. Two variants are protective, while one may be a risk factor. This enhances our understanding of AD genetics and could guide future research and personalized treatments.

Disease trajectories in elders with suspected non-Alzheimer's pathophysiology and its comparison with Alzheimer's disease pathophysiology: a longitudinal study.

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) Aß (A), CSF phosphorylated tau examination (T) and 18F-uorodeoxyglucose 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.

Exploring the links among peripheral immunity, biomarkers, cognition, and neuroimaging in Alzheimer's disease.

INTRODUCTION: We analyzed relationships among peripheral immunity markers, cognition, Alzheimer's disease (AD)-related biomarkers, and neuroimaging to understand peripheral immunity involvement in AD. METHODS: Peripheral immunity markers were assessed in AD, non-AD neurodegenerative disorders, and controls, examining their connections with cognition, AD-related biomarkers, and neuroimaging using multiple regression models. RESULTS: The study included 1579 participants. Higher levels of white blood cell, neutrophil, monocyte, neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic immune-inflammation index (SII), and lower lymphocyte-to-monocyte ratio (LMR) were associated with cognitive decline and more severe anxiety and depression. The impact of lower LMR, lymphocyte count, and higher NLR on cognitive decline is mediated through cerebrospinal fluid amyloid beta (Aß) levels. Additionally, increased PLR, NLR, and SII were associated with brain atrophy and hippocampal Aß deposition (amyloid positron emission tomography). DISCUSSION: Peripheral immunity markers offer a non-invasive and cost-effective means of studying AD-related pathophysiological changes, providing valuable insights into its pathogenesis and treatment. Highlights: Peripheral immunity markers linked to cognitive decline and anxiety/depression.Low LMR, LYM, and high NLR linked to reduced CSF Aß, impacting cognition.High PLR, NLR, SII associated with brain atrophy and hippocampal Aß deposition.

Enhancement of the fluorescence properties via introducing the tetraphenylethylene chromophores into a novel Mn-organic framework with a rare [Mn4(µ3-OH)2] cluster.

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.