Search

Abstract Numerous observational studies suggest associations between proton pump inhibitors (PPIs) and dementia, but causal relationships remain uncertain. Using large-scale genome-wide association study (GWAS) data, we performed univariable Mendelian randomization (UVMR) analysis to assess the causality between five PPI types, and all-cause dementia and its five subtypes. Confounders were controlled through multivariable MR (MVMR) analysis to isolate PPIs’ direct effects on dementia. Heterogeneity and pleiotropy assessments, and leave-one-out analysis, were conducted to validate the robustness of our results. Initial UVMR estimates suggested that lansoprazole (odds ratio [OR] 1.291; 95%confidence interval [CI] 1.001–1.665; p = 0.049) and pantoprazole (OR 1.118; 95% CI 1.014–1.233; p = 0.025) potentially increased VD risk, with their respective direct associations also discovered in MVMR. Additionally, FTD was found to reversely increase rabeprazole use (OR 1.086; 95% CI 1.011–1.167; p = 0.023). However, after adjustment for the false discovery rate (FDR), none of these associations remained statistically significant (pFDR> 0.05). The robustness of our results is supported by consistent estimates across complementary MR methods and the absence of pleiotropy. Our study indicates no robust causality between PPI use and increased dementia risk. Thus, it is inappropriate to restrict clinically justified PPI prescriptions merely due to potential cognitive risks.

Background: Increasing evidence suggests that immunophenotypes play a crucial role in Metabolic dysfunction-associated fatty liver disease (MAFLD), but the specific immunophenotypes contributing to its pathogenesis remain unclear. Objectives: This study aimed to elucidate the causal associations between immunophenotypes and MAFLD and identify the underlying mediation pathways involved. Design: Mendelian randomization (MR) study. Methods: This study is a quasi-causal inference analysis using univariable and multivariable MR (UVMR and MVMR). Five MAFLD genome-wide association studies (GWASs) and the largest immunophenotype GWAS were analyzed to assess their causal associations. Two-step MR identified potential mediators and quantified their mediation proportions. Comprehensive MR methods, multiple sensitivity analyses, meta-analyses, and false discovery rate (FDR) further enhanced the robustness of our findings. Results: Pooled inverse-variance weighted (IVW) estimates in UVMR identified 47 immunophenotypes having a suggestive causal association with MAFLD. After adjusting for FDR, three lymphocyte phenotypes remained significant: CD20 on IgD − CD24 − B cells (OR: 1.035, p fdr : 0.006), terminally differentiated CD8 + T cells %T cells (OR: 1.052, p fdr : 0.006), and CD4 on CD39 + secreting CD4 + regulatory T cells (OR: 1.036, p fdr : 0.046). Meta-analysis of IVW MVMR estimates with confounders adjustment confirmed that CD20 on IgD − CD24 − B cells and terminally differentiated CD8 + T cells %T cells had significant direct causal associations on MAFLD ( p fdr

BackgroundGlucagon-like peptide-1 receptor agonists (GLP-1RAs) have been widely used for type 2 diabetes (T2D) and weight management. However, the causal relationship of GLP-1RAs with erectile dysfunction (ED) was still unclear.MethodsMendelian randomization (MR) analysis was conducted to reveal the association of genetically proxied GLP-1RAs with ED. The proportion of potential mediators mediating GLP-1RAs to ED was also assessed by two-step MR. Finally, a series of sensitivity analyses and Two-Sep cis-MR (TSCMR) were performed to evaluate the robustness of the results.ResultsMR evidence suggested that genetically proxied GLP-1RAs reduced the risk of ED [odds ratio (OR): 0.493; 95% confidence interval (95% CI): 0.430 to 0.565; P

In aquaculture, co-culturing rice with fish may mitigate greenhouse-gas emissions. In this study, co-culture of four rice cultivars in a laboratory-scale rice–fish system reduced CH4 and N2O emissions relative to fish monoculture. Differences in CH4 and N2O emissions among rice cultivars primarily stem from the differential effects of rice plants on plant-mediated CH4 transport, CH4 oxidation and nitrogen absorption.

Echinochloa glabrescens Munro ex Hook. f. is a weed of the genus Echinocloa (Echinocloa spp.) that occurs frequently in paddy fields, causing serious harm to rice production. Florpyrauxifen-benzyl (FPB) is a foliar-applied herbicide used to control Echinocloa spp. in paddy fields. However, in recent years, with the widespread use of FPB in rice production, FPB-resistant barnyard grasses have been reported. Here, we identified an FPB-resistant E. glabrescens population with a resistance index (RI) of 10.65 and conducted a comparative analysis using untargeted metabolomics and transcriptomics to investigate the differences between an FPB-resistant E. glabrescens population and a susceptible E. glabrescens population after treatment with the recommended field dose of FPB. Our results showed that the FPB-resistant E. glabrescens had 115 differentially accumulated metabolites (DAMs; 65 up-regulated and 50 down-regulated) and 6397 differentially expressed genes (DEGs; 65 up-regulated and 50 down-regulated) compared to the susceptible E. glabrescens. The analysis of DAMs and DEGs revealed that DAMs were significantly enriched in Glutathione metabolism, Arginine and proline metabolism, and Zeatin biosynthesis pathways, while DEGs were mainly enriched in carbon fixation in photosynthetic organisms, photosynthesis, cyanoamino acid metabolism and glutathione metabolism, etc. The glutathione metabolism pathway was found to be significantly enriched for both DEGs and DAMs. Within this pathway, the metabolites (spermine) and genes (GSTU8, GSTU18, GSTF1) may play a pivotal role in the resistance mechanism of FPB-resistant E. glabrescens. Furthermore, we demonstrated the presence of GST-mediated metabolic resistance in an FPB-resistant E. glabrescens population by using NBD-Cl. Overall, our study provides new insights into the underlying mechanisms of E. glabrescens resistance to FPB through a comparative analysis of untargeted metabolomics and transcriptomics. Additionally, we identified the GST-mediated metabolic resistance in an FPB-resistant E. glabrescens population, and screened for three candidate genes (GSTU8, GSTU18, GSTF1), which has significant implications for improving the weed management efficacy of FPB in rice production and guiding judicious herbicide usage.

ABSTRACT Objective To assess the proportion of clinically diagnosed MM2‐type sporadic Creutzfeldt–Jakob disease (sCJD) in a Chinese cohort, describe the clinical features of MM2‐cortical (MM2C) and MM2‐thalamic (MM2T) type sCJD to improve the early detection of MM2‐type sCJD. Methods A total of 209 patients with sCJD admitted to the Xuanwu Hospital between February 2012 and August 2022 were reviewed. The patients were classified into probable MM2C, MM2T‐type sCJD, and other types of sCJD according to current clinical diagnostic criteria. Clinical and ancillary data were compared between the groups. Results Fifty‐one (24.4%) patients were clinically diagnosed with MM2‐type sCJD, of which 44 were diagnosed with MM2C‐type sCJD and 7 with MM2T‐type sCJD. In the absence of RT‐QuIC, 27 (61.3%) patients of MM2C‐type sCJD did not meet the US CDC sCJD criteria for possible sCJD on admission, even though the mean period from onset to admission was 6.0 months. However, all of these patients had cortical hyperintensity on DWI. Compared to the other types of sCJD, MM2C‐type sCJD was associated with slower disease progression and the absence of the typical clinical features of sCJD; the MM2T‐type sCJD group had a higher proportion of males, earlier age of onset, longer duration of disease, and a higher incidence of bilateral thalamic hypometabolism/hypoperfusion. Interpretation In the absence of multiple typical sCJD symptoms within 6 months, the presence of cortical hyperintensity on DWI should raise concerns for MM2C‐type sCJD after excluding other etiologies. Bilateral thalamic hypometabolism/hypoperfusion may be more helpful in the clinical diagnosis of MM2T‐type sCJD.

Abstract Background Many geographical areas of sub-Saharan Africa, especially in rural settings, lack complete and up-to-date demographic data, posing a challenge for implementation and evaluation of public health interventions and carrying out large-scale health research. A demographic survey was completed in Mopeia district, located in the Zambezia province in Mozambique, to inform the Broad One Health Endectocide-based Malaria Intervention in Africa (BOHEMIA) cluster randomized clinical trial, which tested ivermectin mass drug administration to humans and/or livestock as a potential novel strategy to decrease malaria transmission. Methods The demographic survey was a prospective descriptive study, which collected data of all the households in the district that accepted to participate. Households were mapped through geolocation and identified with a unique identification number. Basic demographic data of the household members was collected and each person received a permanent identification number for the study. Results 25,550 households were mapped and underwent the demographic survey, and 131,818 individuals were registered in the district. The average household size was 5 members and 76.9% of households identified a male household head. Housing conditions are often substandard with low access to improved water systems and electricity. The reported coverage of malaria interventions was 71.1% for indoor residual spraying and 54.1% for universal coverage of long-lasting insecticidal nets. The median age of the population was 15 years old. There were 910 deaths in the previous 12 months reported, and 43.9% were of children less than 5 years of age. Conclusions The study showed that the district had good coverage of vector control tools against malaria but sub-optimal living conditions and poor access to basic services. The majority of households are led by males and Mopeia Sede/Cuacua is the most populated locality in the district. The population of Mopeia is young (

Abstract Background Behavioral variant frontotemporal dementia (bvFTD) is predominantly considered a dysfunction in cortico-cortical transmission, with limited direct investigation of cortical-subcortical transmission. Thus, we aimed to characterize the metabolic connectivity between areas of the limbic cortico-striato-thalamic-cortical (CSTC) circuit in presymptomatic and symptomatic bvFTD patients. Methods Thirty-three bvFTD patients and 33 unrelated healthy controls were recruited for this study. Additionally, six asymptomatic carriers of the MAPT P301L mutation were compared with 12 non-carriers who were all from the same family of bvFTD. Each participant underwent neuropsychological assessment, genetic testing, and a hybrid PET/MRI scan. Seed-based metabolic connectivity based on [18F]-fluorodeoxyglucose PET between the main components within the limbic CSTC circuit was explored according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Results BvFTD patients exhibited reduced metabolic connectivity between the relays in the limbic CSTC circuit, which included the frontal region (ventromedial prefrontal cortex, orbitofrontal cortex, rectus gyrus, and anterior cingulate cortex), the limbic striatum, and thalamus compared to controls. In the bvFTD patients, the involvement of the limbic CSTC circuit was associated with the severity of behavior disruption, as measured by the frontal behavior inventory, the disinhibition subscale, and the apathy subscale. Notably, asymptomatic MAPT carriers had weakened frontostriatal connectivity but enhanced striatothalamus and thalamofrontal connectivity within the limbic CSTC circuit compared with noncarriers. Conclusion These findings suggested that aberrant metabolic connectivity within the limbic CSTC circuit is present in symptomatic and even asymptomatic stages of bvFTD. Thus, metabolic connectivity patterns could be used as a potential biomarker to detect the presymptomatic stage and track disease progression.

Introduction The wealth index is widely used as a proxy for a household’s socioeconomic position (SEP) and living standard. This work constructs a wealth index for the Mopeia district in Mozambique using data collected in year 2021 under the BOHEMIA (Broad One Health Endectocide-based Malaria Intervention in Africa) project.Methods We evaluate the performance of three alternative approaches against the Demographic and Health Survey (DHS) method based wealth index: feature selection principal components analysis (PCA), sparse PCA and robust PCA. The internal coherence between four wealth indices is investigated through statistical testing. Validation and an evaluation of the stability of the wealth index are performed with additional household income data from the BOHEMIA Health Economics Survey and the 2018 Malaria Indicator Survey data in Mozambique.Results The Spearman’s rank correlation between wealth index ventiles from four methods is over 0.98, indicating a high consistency in results across methods. Wealth rankings and households’ income show a strong concordance with the area under the curve value of ~0.7 in the receiver operating characteristic analysis. The agreement between the alternative wealth indices and the DHS wealth index demonstrates the stability in rankings from the alternative methods.Conclusions This study creates a wealth index for Mopeia, Mozambique, and shows that DHS method based wealth index is an appropriate proxy for the SEP in low-income regions. However, this research recommends feature selection PCA over the DHS method since it uses fewer asset indicators and constructs a high-quality wealth index.

Abstract The chromosome 9 open reading frame 72 (C9ORF72) has been proposed as the causative gene of frontotemporal dementia with parkinsonism (FTDP), but its pathophysiological mechanism of parkinsonism is poorly understood. To explore the roles of striatal motor subdivisions in the pathogenesis of parkinsonism resulting from C9ORF72 repeat expansions in the FTDP, two patients with FTDP from one pedigree and seventeen healthy controls were enrolled. The participants received clinical interviews, physical examinations, genetic testing, [18F]-fluorodeoxyglucose PET/MRI, and [18F]-dihydrotetrabenazine PET/CT. Voxel-wise and region of interest analysis were conducted with respect to gray matter volume, metabolism, and dopamine transport function between patients and controls, focusing on the motor part of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. Patient 1 presented with parkinsonism as the initial symptom, while patient 2 exhibited behavior disturbance as the first symptom, followed by parkinsonism within one year. Both patients had the hexanucleotide expansion detected in C9ORF72(>52 repeats). Gray matter volume atrophy, hypometabolism and dopamine dysfunction were observed in the motor areas of the striatum. Of the two patients, marked glucose hypometabolism within the striatal motor subregion was observed in patient 1, with corresponding gray matter atrophy. In addition, presynaptic dopaminergic integrity of patient 2 was deteriorated in the motor subregions which was consistent with gray matter atrophy. These findings imply that parkinsonism in FTDP may be associated with the degeneration and dopaminergic dysfunction of the striatal motor subregion, which might be attributed to C9orf72 repeat expansions.

Abstract We present the first complete next-to-leading-order (NLO) prediction with full jet algorithm implementation for the single inclusive jet production in pA collisions at forward rapidities within the color glass condensate (CGC) effective theory. Our prediction is fully differential over the final state physical kinematics, which allows the implementation of any infra-red safe observable including the jet clustering procedure. The NLO calculation is organized with the aid of the observable originated power counting proposed in [1] which gives rise to the novel soft contributions in the CGC factorization. We achieve the fully-differential calculation by constructing suitable subtraction terms to handle the singularities in the real corrections. The subtraction contributions can be exactly integrated analytically. We present the NLO cross section with the jets constructed using the anti-k T algorithm. The NLO calculation demonstrates explicitly the validity of the CGC factorization in jet production. Furthermore, as a byproduct of the subtraction method, we also derive the fully analytic cross section for the forward jet production in the small-R limit. We show that in the small-R approximation, the forward jet cross section can be factorized into a semi-hard cross section that produces a parton and the semi-inclusive jet functions (siJFs). We argue that this feature holds for generic jet production and jet substructure observables in the CGC framework. Last, we show numerical analyses of the derived formula to validate our calculations. We justify when the small-R approximation is appropriate. Like forward hadron production, the obtained NLO result also exhibits the negativity of the cross section in the large jet transverse regime, which signals the need for the threshold resummation. A sketch of the threshold resummation in the CGC framework is presented based on the multiple emission picture and it is found to agree with the approach using the rapidity renormalization group equation developed in [2].

Abstract Background To elucidate the clinical and ancillary features of genetic prion diseases (gPrDs) presenting with frontotemporal dementia (FTD) to aid early identification. Methods Global data of gPrDs presenting with FTD caused by prion protein gene mutations were collected from literature review and our records. Fifty-one cases of typical FTD and 136 cases of prion diseases admitted to our institution were included as controls. Clinical and ancillary data of the different groups were compared. Results Forty-nine cases of gPrDs presenting with FTD were identified. Compared to FTD or prion diseases, gPrDs presenting with FTD were characterized by earlier onset age (median 45 vs. 61/60 years, P < 0.001, P < 0.001) and higher incidence of positive family history (81.6% vs. 27.5/13.2%, P < 0.001, P < 0.001). Furthermore, GPrDs presenting with FTD exhibited shorter duration (median 5 vs. 8 years) and a higher rate of parkinsonism (63.7% vs. 9.8%, P < 0.001), pyramidal signs (39.1% vs. 7.8%, P = 0.001), mutism (35.9% vs. 0%, P < 0.001), seizures (25.8% vs. 0%, P < 0.001), myoclonus (22.5% vs. 0%, P < 0.001), and hyperintensity on MRI (25.0% vs. 0, P < 0.001) compared to FTD. Compared to prion diseases, gPrDs presenting with FTD had a longer duration of symptoms (median 5 vs. 1.1 years, P < 0.001), higher rates of frontotemporal atrophy (89.7% vs. 3.3%, P < 0.001), lower rates of periodic short-wave complexes on EEG (0% vs. 30.3%, P = 0.001), and hyperintensity on MRI (25.0% vs. 83.0%, P < 0.001). The frequency of codon 129 Val allele in gPrDs presenting with FTD was significantly higher than that reported in the literature for gPrDs in the Caucasian and East Asian populations (33.3% vs. 19.2%/8.0%, P = 0.005, P < 0.001). Conclusions GPrDs presenting with FTD are characterized by early-onset, high incidence of positive family history, high frequency of the Val allele at codon 129, overlapping symptoms with prion disease and FTD, and ancillary features closer to FTD. PRNP mutations may be a rare cause in the FTD spectrum, and PRNP genotyping should be considered in patients with these features.

Abstract Background Studies exploring topological properties of the metabolic network during the presymptomatic stage of genetic frontotemporal dementia (FTD) are scarce. However, such knowledge is important for understanding brain function and disease pathogenesis. Therefore, we aimed to explore FTD-specific patterns of metabolism topology reconfiguration in microtubule-associated protein tau (MAPT) mutation carriers before the onset of symptoms. Methods Six asymptomatic carriers of the MAPT P301L mutation were compared with 12 non-carriers who all belonged to the same family of FTD. For comparison, we included 32 behavioral variant FTD (bvFTD) patients and 33 unrelated healthy controls. Each participant underwent neuropsychological assessments, genetic testing, and a hybrid positron emission tomography (PET)/magnetic resonance imaging (MRI) scan. Voxel-wise gray matter volumes and standardized uptake value ratios were calculated and compared for structural MRI and fluorodeoxyglucose (FDG)-PET, separately. The sparse inverse covariance estimation method (SICE) was applied to topological properties and metabolic connectomes of brain functional networks derived from 18F-FDG PET/MRI data. Independent component analysis was used to explore the metabolic connectivity of the salience (SN) and default mode networks (DMN). Results The asymptomatic MAPT carriers performed normal global parameters of the metabolism network, whereas bvFTD patients did not. However, we revealed lost hubs in the ventromedial prefrontal, orbitofrontal, and anterior cingulate cortices and reconfigured hubs in the anterior insula, precuneus, and posterior cingulate cortex in asymptomatic carriers compared with non-carriers, which overlapped with the comparisons between bvFTD patients and controls. Similarly, significant differences in local parameters of these nodes were present between asymptomatic carriers and non-carriers. The reduction in the connectivity of lost hub regions and the enhancement of connectivity between reconfigured hubs and components of the frontal cortex were marked during the asymptomatic stage. Metabolic connectivity within the SN and DMN was enhanced in asymptomatic carriers compared with non-mutation carriers but reduced in bvFTD patients relative to controls. Conclusions Our findings showed that metabolism topology reconfiguration, characterized by the earliest involvement of medial prefrontal areas and active compensation in task-related regions, was present in the presymptomatic phase of genetic FTD with MAPT mutation, which may be used as an imaging biomarker of increased risk of FTD.

IntroductionHereditary spastic paraplegias (HSPs) are genetic neurodegenerative diseases. The most common form of pure HSP that is inherited in an autosomal dominant manner is spastic paraplegia type 4 (SPG4), which is caused by mutations in the SPAST gene. Different theories have been proposed as the mechanism underlying SPAST-HSP for different types of genetic mutations, including gain- and loss-of-function mechanisms. To better understand the mutation mechanisms, we performed genetic analysis and investigated a truncating SPAST variant that segregated with disease in one family.Objectives and methodsWe described a pure HSP pedigree with family members across four generations. We performed genetic analysis and investigated a novel frameshift pathogenic variant (c.862_863dupAC, p. H289Lfs*27) in this family. We performed reverse transcription-polymerase chain reaction (RT-PCR), Sanger sequencing, and quantitative RT-PCR using total RNA from an Epstein-Barr virus-induced lymphoblastoid cell line produced from the proband. We also performed Western blotting on cell lysates to investigate if the protein expression of spastin is affected by this variant.ResultsThis variant (c.862_863dupAC, p. H289Lfs*27) co-segregated with pure HSP in this family and is not registered in any public database. Measurement of SPAST transcripts in lymphoblasts from the proband demonstrated a reduction of SPAST transcript levels through likely nonsense-mediated mRNA decay. Immunoblot analyses demonstrated a reduction of spastin protein expression levels in lymphoblasts.ConclusionWe report an SPG4 family with a novel heterozygous frameshift variant p.H289Lfs*27 in SPAST. Our study implies haploinsufficiency as the pathogenic mechanism for this variant and expands the known mutation spectrum of SPAST.

The normal operation of aircraft and flights can be affected by various unpredictable factors, such as severe weather, airport closure, and corrective maintenance, leading to disruption of the planned schedule. When a disruption occurs, the airline operation control center performs various operations to reassign resources (e.g., flights, aircraft, and crews) and redistribute passengers to restore the schedule while minimizing costs. We introduce different sources of disruption and corresponding operations. Then, basic models and recently proposed extensions for aircraft recovery, crew recovery, and integrated recovery are reviewed, with the aim of providing models and methods for different disruption scenarios in the practical implementation of airlines. In addition, we provide suggestions for future research directions in these topics.

Background: Insomnia and thalamic involvement were frequently reported in patients with genetic Creutzfeldt-Jakob disease (gCJD) with E200K mutations, suggesting E200K might have discrepancy with typical sporadic CJD (sCJD). The study aimed to explore the clinical and neuroimage characteristics of genetic E200K CJD patients by comprehensive neuroimage analysis. Methods: Six patients with gCJD carried E200K mutation on Prion Protein (PRNP) gene, 13 patients with sporadic CJD, and 22 age- and sex-matched normal controls were enrolled in the study. All participants completed a hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) examination. Signal intensity on diffusion-weighted imaging (DWI) and metabolism on PET were visually rating analyzed, statistical parameter mapping analysis was performed on PET and 3D-T1 images. Clinical and imaging characteristics were compared between the E200K, sCJD, and control groups. Results: There was no group difference in age or gender among the E200K, sCJD, and control groups. Insomnia was a primary complaint in patients with E200K gCJD (4/2 versus 1/12, p = 0.007). Hyperintensity on DWI and hypometabolism on PET of the thalamus were observed during visual rating analysis of images in patients with E200K gCJD. Gray matter atrophy (uncorrected p

Background: Dysfunction of the thalamus has been proposed as a core mechanism of fatal familial insomnia. However, detailed metabolic and structural alterations in thalamic subnuclei are not well documented. We aimed to address the multimodal structuro-metabolic pattern at the level of the thalamic nuclei in fatal familial insomnia patients, and investigated the clinical presentation of primary thalamic alterations. Materials and Methods: Five fatal familial insomnia patients and 10 healthy controls were enrolled in this study. All participants underwent neuropsychological assessments, polysomnography, electroencephalogram, and cerebrospinal fluid tests. MRI and fluorodeoxyglucose PET were acquired on a hybrid PET/MRI system. Structural and metabolic changes were compared using voxel-based morphometry analyses and standardized uptake value ratio analyses, focusing on thalamic subnuclei region of interest analyses. Correlation analysis was conducted between gray matter volume and metabolic decrease ratios, and clinical features. Results: The whole-brain analysis showed that gray matter volume decline was confined to the bilateral thalamus and right middle temporal pole in fatal familial insomnia patients, whereas hypometabolism was observed in the bilateral thalamus, basal ganglia, and widespread cortices, mainly in the forebrain. In the regions of interest analysis, gray matter volume and metabolism decreases were prominent in bilateral medial dorsal nuclei, anterior nuclei, and the pulvinar, which is consistent with neuropathological and clinical findings. A positive correlation was found between gray matter volume and metabolic decrease ratios. Conclusions: Our study revealed specific structuro-metabolic pattern of fatal familial insomnia that demonstrated the essential roles of medial dorsal nuclei, anterior nuclei, and pulvinar, which may be a potential biomarker in diagnosis. Also, primary thalamic subnuclei alterations may be correlated with insomnia, neuropsychiatric, and autonomic symptoms sparing primary cortical involvement.

BackgroundBehavioral variant frontotemporal dementia (bvFTD) is a clinically heterogeneous syndrome with high heredity. However, the frequencies of mutations associated with bvFTD have yet to be determined. The aim of the current study was to investigate the frequency of Chinese Han patients harboring genetic bvFTD variants.MethodsA total of 49 bvFTD patients selected from our frontotemporal lobar degeneration database, including 14 familial cases belonging to eight families and 35 sporadic cases were consecutively recruited from July 2014 to December 2019 at Xuanwu Hospital (Beijing, China). Whole-exome sequencing (WES) was performed and repeat-primed PCR was used to test samples for the C9orf72 hexanucleotide repeat expansion mutation. The frequency of genetic variants and the pathogenicity of the novel variants were analyzed.ResultsTen pathogenic or likely pathogenic variants were identified in 17 bvFTD patients, including C9orf72 repeat expansions, six previously reported mutations and three novel mutations (MAPT p. R5C, p. D54N, GRN p. P451L). Genetic mutations accounted for 27.9% (12/43) of total cases, 87.5% (7/8) of patients with familial bvFTD, and 14.3% (5/35) with sporadic bvFTD. Pathogenic variants mostly occurred in MAPT gene (20.9%, 9/43), followed by C9orf72 repeat expansions (2.3%, 1/43), GRN gene (2.3%, 1/43) and FUS gene (2.3%, 1/43).ConclusionThere was a high prevalence of genetic variants in Chinese bvFTD patients, highlighting the necessity of genetic testing for bvFTD.

ObjectiveThe objective of the study was to explore patterns of white matter (WM) alteration in preclinical stage familial Creutzfeldt–Jakob disease (fCJD) using diffusion tensor imaging (DTI).MethodsSeven asymptomatic carriers of the PRNP G114V mutation and six non-carriers were recruited from the same fCJD kindred and follow-up obtained from all asymptomatic carriers and two non-carriers 2 years later. Overlapping WM patterns were also explored in asymptomatic carriers and symptomatic CJD patients. All participants underwent clinical and neuropsychological assessments and DTI at baseline and follow-up. DTI data were subjected to whole-brain voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) in WM using tract-based spatial statistics. Three comparisons were conducted: baseline carriers against non-carriers (baseline analysis), changes after 2 years in carriers (follow-up analysis), and differences between patients with symptomatic CJD and healthy controls (CJD patient analysis).ResultsNeither carriers nor non-carriers developed any neurological symptoms during 2 years of follow-up. Baseline analysis showed no differences between the carrier and non-carrier groups in MD and FA. Follow-up analysis showed significantly increased MD in multiple WM tracts, among which increased MD in the bilateral superior longitudinal fasciculus, bilateral anterior thalamic radiation, bilateral cingulate gyrus, and left uncinate fasciculus overlapped the patterns observed in patients with symptomatic CJD.ConclusionChanges in integrity within multiple WM tracts can be detected during the preclinical stage of fCJD.

Posterior cortical atrophy (PCA) is widely considered as an atypical variant of Alzheimer disease and is characterized by a progressive decline in visual function. PCA has been investigated from the standpoints of brain structure and metabolism, but tau deposition and its relationship to disease severity still remain unclear. Here, we used a novel tau ligand, [18F]PI2620, to visualize tau deposition in a PCA patient. The results showed that high [18F]PI2620 uptake in posterior cortical regions was associated with clinical manifestations, morphologic changes in the brain observed by magnetic resonance imaging (MRI), and hypometabolism detected by [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET). This is the first report demonstrating a clinical anatomical correspondence between [18F]PI2620 PET results, clinical manifestations, MRI, and [18F]FDG PET findings in a Chinese patient with PCA. The results also support the utility of [18F]PI2620 for visualizing tau aggregation in PCA.

Proteins are the primary functional agents in all cellular processes, facilitating various functions such as enzymes and structure-forming or signal-transducing molecules. In this work, we report a fluorescent dye, PyMDI-Zn, which could specifically bind with proteins and provide a red-shifted fluorescent emission. The visual analysis of protein in sodium dodecyl sulfate-polyacrylamide gel electrophoresis could be realized in 5 min by using PyMDI-Zn as a light-up dye. Based on its cell penetration and low toxicity, PyMDI-Zn could also be applied to locate protein-rich regions and organelles in live cell imaging. Moreover, the direct protein quantitation can be realized based on PyMDI-Zn, providing a method of screening for food adulteration by nitrogen-rich compounds.

Background Understanding hub genes involved in gastric cancer (GC) metastasis could lead to effective approaches to diagnose and treat cancer. In this study, we aim to identify the hub genes and investigate the underlying molecular mechanisms of GC. Methods To explore potential therapeutic targets for GC,three expression profiles (GSE54129, GSE33651, GSE81948) of the genes were extracted from the Gene Expression Omnibus (GEO) database. The GEO2R online tool was applied to screen out differentially expressed genes (DEGs) between GC and normal gastric samples. Database for Annotation, Visualization and Integrated Discovery was applied to perform Gene Ontology (GO) and KEGG pathway enrichment analysis. The protein-protein interaction (PPI) network of these DEGs was constructed using a STRING online software. The hub genes were identified by the CytoHubba plugin of Cytoscape software. Then, the prognostic value of these identified genes was verified by gastric cancer database derived from Kaplan-Meier plotter platform. Results A total of 85 overlapped upregulated genes and 44 downregulated genes were identified. The majority of the DEGs were enriched in extracellular matrix organization, endodermal cell differentiation, and endoderm formation. Moreover, five KEGG pathways were significantly enriched, including ECM-receptor interaction, amoebiasis, AGE-RAGE signaling pathway in diabetic complications, focal adhesion, protein digestion and absorption. By combining the results of PPI network and CytoHubba, a total of nine hub genes including COL1A1, THBS1, MMP2, CXCL8, FN1, TIMP1, SPARC, COL4A1, and ITGA5 were selected. The Kaplan-Meier plotter database confirmed that overexpression levels of these genes were associated with reduced overall survival, except for THBS1 and CXCL8. Conclusions Our study suggests that COL1A1, MMP2, FN1, TIMP1, SPARC, COL4A1, and ITGA5 may be potential biomarkers and therapeutic targets for GC. Further study is needed to assess the effect of THBS1 and CXCL8 on GC.

This study aims to investigate the protective effects of BlingLife®-berry extract on the eyes. BlingLife®-berry extract is a mixture of high-quality natural berries, including blackcurrant, aromia, bilberry and maquiberry. The main active ingredient responsible for theeye-protective effects is anthocyanins. Anthocyanins are natural water-soluble pigments belonging to the flavonoid class, and theyhave multiple benefits, including improving vision, anti-inflammatory and antibacterial properties, and antioxidant effects. Dueto the dual benefits of anthocyanins in protecting vision and eliminating free radicals, this study explores the comprehensive eye protective effects of BlingLife®-berry extract in terms of combating blue light-induced eye damage and oxidative stress-inducedvisual fatigue. The results provide robust evidence for the in vivo effects and further technological applications of BlingLife®-berry extract. [ABSTRACT FROM AUTHOR]