Atrophy network mapping of clinical subtypes and main symptoms in frontotemporal dementia.

Frontotemporal Dementia (FTD) is a disease of high heterogeneity, apathy and disinhibition present in all subtypes of FTD and imposes a significant burden on families/society. Traditional neuroimaging analysis has limitations in elucidating the network localization due to individual clinical and neuroanatomical variability. The study aims to identify the atrophy network map associated with different FTD clinical subtypes and determine the specific localization of the network for apathy and disinhibition. Eighty FTD patients [45 behavioral variant FTD (bvFTD) and 35 semantic variant progressive primary aphasia (svPPA)] and 58 healthy controls (HCs) at Xuanwu Hospital were enrolled as Dataset 1; 112 FTD patients including 50 bvFTD, 32 svPPA, and 30 non-fluent variant PPA (nfvPPA) cases, and 110 HCs from Frontotemporal Lobar Degeneration Neuroimaging Initiative (FTLDNI) dataset were included as Dataset 2. Initially, single-subject atrophy maps were defined by comparing cortical thickness in each FTD patient versus HCs. Next, the network of brain regions functionally connected to each FTD patient's location of atrophy was determined using seed-based functional connectivity in a large (n = 1000) normative connectome. Finally, we used atrophy network mapping to define clinical subtype-specific network (45 bvFTD, 35 svPPA and 58 HCs in Dataset 1; 50 bvFTD, 32 svPPA, 30 nfvPPA and 110 HCs in Dataset 2) and symptom-specific networks [combined dataset 1 and 2, apathy without depression Vs non-apathy without depression (80:26), disinhibition Vs non-disinhibition (88:68)]. We compare the result with matched symptom networks derived from patients with focal brain lesions or conjunction analysis. Through the analysis of two datasets, we identified heterogeneity in atrophy patterns among FTD patients. However, these atrophy patterns are connected to a common brain network. The primary regions affected by atrophy in FTD included the frontal and temporal lobes, particularly the anterior temporal lobe. bvFTD connects to frontal and temporal cortical areas, svPPA mainly impacts the anterior temporal region, and nfvPPA targets the inferior frontal gyrus and precentral cortex regions. The apathy-specific network was localized in the orbital frontal cortex and ventral striatum, while the disinhibition-specific network was localized in the bilateral orbital frontal gyrus and right temporal lobe. Apathy and disinhibition atrophy networks resemble known motivational and criminal lesion networks respectively. A significant correlation was found between the apathy/disinhibition scores and functional connectivity between atrophy maps and the peak of the networks. This study localizes the common network of clinical subtypes and main symptoms in FTD, guiding future FTD neuromodulation interventions.

Genetic insights into drug targets for sporadic Creutzfeldt-Jakob disease: Integrative multi-omics analysis.

OBJECTIVE: Sporadic Creutzfeldt-Jakob disease (sCJD) is a fatal rapidly progressive neurodegenerative disorder with no effective therapeutic interventions. We aimed to identify potential genetically-supported drug targets for sCJD by integrating multi-omics data. METHODS: Multi-omics-wide association studies, Mendelian randomization, and colocalization analyses were employed to explore potential therapeutic targets using expression, single-cell expression, DNA methylation, and protein quantitative trait locus data from blood and brain tissues. Outcome data was from a case-control genome-wide association study, which included 4110 sCJD patients and 13,569 controls. Further investigations encompassed druggability, potential side effects, and associated biological pathways of the identified targets. RESULTS: Integrative multi-omics analysis identified 23 potential therapeutic targets for sCJD, with five targets (STX6, XYLT2, PDIA4, FUCA2, KIAA1614) having higher levels of evidence. One target (XYLT2) shows promise for repurposing, two targets (XYLT2, PDIA4) are druggable, and three (STX6, KIAA1614, and FUCA2) targets represent potential future breakthrough points. The expression level of STX6 and XYLT2 in neurons and oligodendrocytes was closely associated with an increased risk of sCJD. Brain regions with high expression of STX6 or causal links to sCJD were often those areas commonly affected by sCJD. CONCLUSIONS: Our study identified five potential therapeutic targets for sCJD. Further investigations are warranted to elucidate the mechanisms underlying the new targets for developing disease therapies or initiate clinical trials.

Regional Glymphatic Abnormality in Behavioral Variant Frontotemporal Dementia.

OBJECTIVES: Glymphatic function has not yet been explored in behavioral variant frontotemporal dementia (bvFTD). The spatial correlation between regional glymphatic function and bvFTD remains unknown. METHOD: A total of 74 patients with bvFTD and 67 age- and sex-matched healthy controls (HCs) were selected from discovery dataset and replication dataset. All participants underwent neuropsychological assessment. Glymphatic measures including choroid plexus (CP) volume, diffusion tensor imaging along the perivascular (DTI-ALPS) index, and coupling between blood-oxygen-level-dependent signals and cerebrospinal fluid signals (BOLD-CSF coupling), were compared between the two groups. Regional glymphatic function was evaluated by dividing DTI-ALPS and BOLD-CSF coupling into anterior, middle, and posterior regions. The bvFTD-related metabolic pattern was identified using spatial covariance analysis based on l8 F-FDG-PET. RESULTS: Patients with bvFTD showed higher CP volume (p < 0.001); anterior and middle DTI-ALPS (p < 0.001); and weaker anterior BOLD-CSF coupling (p < 0.05) than HCs after controlling for cortical gray matter volume in both datasets. In bvFTD from the discovery dataset, the anterior DTI-ALPS was negatively associated with the expression of the bvFTD-related metabolic pattern (r = -0.52, p = 0.034) and positively related with regional standardized uptake value ratios of l8 F-FDG-PET in bvFTD-related brain regions (r range: 0.49 to 0.62, p range: 0.017 to 0.047). Anterior and middle glymphatic functions were related to global cognition and disease severity. INTERPRETATION: Our findings reveal abnormal glymphatic function, especially in the anterior and middle regions of brain in bvFTD. Regional glymphatic dysfunction may contribute to the pathogenesis of bvFTD. ANN NEUROL 2023;94:442-456.

Optimizing Skim Milk Yogurt Properties: Combined Impact of Trans-glutaminase and Protein-Glutaminase.

The lack of fat in yogurt can lead to alterations in taste and whey separation, reducing consumer acceptance. In this study, the feasibility of enhancing the quality of skim milk yogurt through a combination of transglutaminase (TG) and protein-glutaminase (PG) was investigated. The combination of TG and PG resulted in simultaneous cross-linking and deamidated of casein micelles, with PG deamidation taking priority over TG cross-linking, leading to higher solubility and lower turbidity of milk proteins compared with TG alone. When 0.06 U/mL TG and 0.03 U/mL PG were added, firmness and viscosity indexes significantly increased by 38.26 and 78.59%, respectively as compared with the control. Microscopic images revealed increased cross-linking with casein and filling of cavities by smaller sub-micelles in the combination of TG and PG treatment. Furthermore, the combination of TG and PG resolved issues of rough taste and whey separation, leading to improved overall liking. This study highlights the benefits of using both enzymes in dairy production and has important implication for future research.

Peripheral inflammation in behavioural variant frontotemporal dementia: associations with central degeneration and clinical measures.

BACKGROUND: Neuroinflammation plays a significant role in the progression of frontotemporal dementia (FTD). However, the association between peripheral inflammatory factors and brain neurodegeneration is poorly understood. We aimed to examine changes in peripheral inflammatory markers in patients with behavioural variant FTD (bvFTD) and explore the potential association between peripheral inflammation and brain structure, metabolism, and clinical parameters. METHODS: Thirty-nine bvFTD patients and 40 healthy controls were enrolled and underwent assessment of plasma inflammatory factors, positron emission tomography/magnetic resonance imaging, and neuropsychological assessments. Group differences were tested using Student's t test, Mann‒Whitney U test, or ANOVA. Partial correlation analysis and multivariable regression analysis were implemented using age and sex as covariates to explore the association between peripheral inflammatory markers, neuroimaging, and clinical measures. The false discovery rate was used to correct for the multiple correlation test. RESULTS: Plasma levels of six factors, including interleukin (IL)-2, IL-12p70, IL-17A, tumour necrosis superfamily member 13B (TNFSF/BAFF), TNFSF12 (TWEAK), and TNFRSF8 (sCD30), were increased in the bvFTD group. Five factors were significantly associated with central degeneration, including IL-2, IL-12p70, IL-17A, sCD30/TNFRSF8, and tumour necrosis factor (TNF)-α; the association between inflammation and brain atrophy was mainly distributed in frontal-limbic-striatal brain regions, whereas the association with brain metabolism was mainly in the frontal-temporal-limbic-striatal regions. BAFF/TNFSF13B, IL-4, IL-6, IL-17A and TNF-α were found to correlate with clinical measures. CONCLUSION: Peripheral inflammation disturbance in patients with bvFTD participates in disease-specific pathophysiological mechanisms, which could be a promising target for diagnosis, treatment, and monitoring therapeutic efficacy.

Long-Term Flexible Neural Interface for Synchronous Recording of Cross-Regional Sensory Processing along the Olfactory Pathway.

Humans perceive the world through five senses, of which olfaction is the oldest evolutionary sense that enables the detection of chemicals in the external environment. Recent progress in bioinspired electronics has boosted the development of artificial sensory systems. Here, a biohybrid olfactory system is proposed by integrating living mammals with implantable flexible neural electrodes, to employ the outstanding properties of mammalian olfactory system. In olfactory perception, the peripheral organ-olfactory epithelium (OE) projects axons into the olfactory relay station-olfactory bulb (OB). The olfactory information encoded in the neural activity is recorded from both OE and OB simultaneously using flexible neural electrodes. Results reveal that spontaneous slow oscillations (<12 Hz) in both OE and OB closely follow respiration. This respiration-locked rhythm modulates the amplitude of fast oscillations (>20 Hz), which are associated with odor perception. Further, by extracting the characteristics of odor-evoked oscillatory signals, responses of different odors are identified and classified with 80% accuracy. This study demonstrates for the first time that the flexible electrode enables chronic stable electrophysiological recordings of the peripheral and central olfactory system in vivo. Overall, the method provides a novel neural interface for olfactory biosensing and cognitive processing.

Involvement of specific striatal subregion contributes to executive deficits in Alzheimer disease.

BACKGROUND: There is growing evidence that the striatum plays a central role in cognitive dysfunction. However, it remains unclear whether and how the striatum contributes specifically to executive deficits in Alzheimer disease (AD). We sought to elucidate aberrations in the striatal subregion associated with executive function and its metabolic connectivity with the cortical regions to investigate its role in the pathogenesis of executive deficits in patients with AD. METHODS: Patients with AD and healthy controls underwent a neuropsychological assessment battery, including assessment of executive function, and a hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) scan. We performed voxel-wise analyses of cerebral metabolism between patients and controls, focusing on the executive subregion of the striatum according to the Oxford-GSK-Imanova Striatal Connectivity Atlas. We assessed the correlation between the [18F]-fluorodeoxyglucose standardized uptake value ratio of the striatal executive subregion and clinical variables, and we analyzed seed-based metabolic connectivity of the striatal executive subregion with the dorsolateral prefrontal cortex (DLPFC) using [18F]-fluorodeoxyglucose PET. RESULTS: We included 50 patients with AD and 33 controls in our analyses. The patterns of striatal hypometabolism in patients with AD were specific to executive and caudal motor subregions. Metabolic activity in the executive subregion of the striatum correlated negatively with the severity of executive dysfunction, as measured with the Trial-Making Test (TMT) part B and the difference score TMT B-A, and correlated positively with Digit Span (backward) and Verbal Fluency Test scales, particularly on the left side. Compared with controls, patients with AD showed reduced metabolic connectivity between striatal executive subregions and the dorsolateral prefrontal cortex (DLPFC). LIMITATIONS: Our study was limited by small sample sizes and cross-sectional findings. CONCLUSION: Our findings show that patients with AD have impairments in the executive subregion of the striatum, and these deficits may be associated with a disconnection between the executive striatum and DLPFC, providing valuable insight into the pathogenesis of this disease.

A robust colorimetric aptasensor for the label-free detection of marine toxins based on tyrosine-capped gold nanoparticles.

PbTx-2 and okadaic acid (OA) are two typical marine toxins that are highly toxic and harmful to human health. The approach based on citrate-capped gold nanoparticles (Cit-AuNPs) and specific aptamers to construct label-free colorimetric sensors is a widely used method for marine toxin detection. However, the potential interactions between Cit-AuNPs and target molecules have always been ignored, which may result in wrong analytical results due to shortcomings in the Cit-AuNPs. To overcome these shortfalls, in this work, AuNPs were synthesized using tyrosine as a reducing and capping agent, and a robust colorimetric aptasensor based on tyrosine-capped AuNPs (Tyr-AuNPs) was constructed for the label-free detection of marine toxins. Tyr-AuNPs presented better stability compared to Cit-AuNPs due to the stronger binding of amine groups on tyrosine to AuNPs through the Au-N bond. Interactions between Tyr-AuNPs and PbTx-2 were analyzed through UV-vis and isothermal titration calorimetry methods and the results validated the robustness of the Tyr-AuNPs. Colorimetric aptasensors were established for PbTx-2 and OA detection with a linear range of 0.05-4 ppm and limits of detection of 2.25 ppb and 5.19 ppb, respectively. These results demonstrate that the developed colorimetric aptasensor can be a robust and promising method for marine toxin detection.

Curdlan production from cassava starch hydrolysates by Agrobacterium sp. DH-2.

Curdlan is an edible microbial polysaccharide and can be used in food, biomedical and biomaterial fields. To reduce the cost of curdlan production, this study investigated the suitability of cassava starch hydrolysates as carbon source for curdlan production. Cassava starch was hydrolyzed into maltose syrup using ß-amylase and pullulanase at various enzyme dosages, temperature, time and addition order of two enzymes. The maltose yield of 53.17% was achieved at starch loading 30% by simultaneous addition ß-amylase 210 U/g starch and pullulanase 3 U/g starch at 60 °C for 9 h. Cassava starch hydrolysates were used as carbon source for curdlan production by Agrobacterium sp. DH-2. The curdlan production reached 28.4 g/L with the yield of 0.79 g/g consumed sugar and molecular weight of 1.26 × 106 Da at 96 h with cassava starch hydrolysate at 90 g/L initial sugar concentration. Curdlan produced from cassava starch hydrolysates was characterized using FT-IR spectra and thermo gravimetric analysis. This work indicated that cassava starch was a potential renewable feedstock for curdlan production.

Surface acoustic wave (SAW) techniques in tissue engineering.

Recently, the introduction of surface acoustic wave (SAW) technique for microfluidics has drawn a lot of attention. The pattern and mutual communication in cell layers, tissues, and organs play a critical role in tissue homeostasis and regeneration and may contribute to disease occurrence and progression. Tissue engineering aims to repair and regenerate damaged organs, depending on biomimetic scaffolds and advanced fabrication technology. However, traditional bioengineering synthesis approaches are time-consuming, heterogeneous, and unmanageable. It is hard to pattern cells in scaffolds effectively with no impact on cell viability and function. Here, we summarize a biocompatible, easily available, label-free, and non-invasive tool, surface acoustic wave (SAW) technique, which is getting a lot of attention in tissue engineering. SAW technique can realize accurate sorting, manipulation, and cells' pattern and rapid formation of spheroids. By integrating several SAW devices onto lab-on-a-chip platforms, tissue engineering lab-on-a-chip system was proposed. To the best of our knowledge, this is the first report to summarize the application of this novel technique in the field of tissue engineering.

Effects of carbon sources on production and properties of curdlan using Agrobaterium sp. DH-2.

Curdlan has wide potential application in the food and biomedical fields due to its unique thermal gel and biological activity. This study investigated the effect of six sugars including glucose, fructose, lactose, maltose, sucrose and xylose as carbon sources on production and properties of curdlan using Agrobacterium sp. DH-2. The maximum production (38.1 g/L and 37.4 g/L, respectively) and yield (0.58 g curdlan/g sucrose and 0.53 g curdlan/g maltose, respectively) of curdlan were achieved by sucrose and maltose, followed by glucose, fructose, lactose and xylose. Scanning electron micrographs showed that the surface of cells was smooth in strain growth phase, while cells were covered by curdlan matrix acted as a net in the curdlan synthesis phase. The highest glucosyltransferase activity (19.9 U/g biomass) corresponded to the maximum curdlan production using the sucrose medium. The molecular weight and gel strength of curdlan were influenced by the carbon sources. The curdlan from xylose medium resulted in a maximum molecular weight of 1.59 × 106 Da and the highest gel strength of 989.2 g/cm2, while the curdlan from sucrose medium resulted in a lowest molecular weight of 1.10 × 106 Da and gel strength of 672.8 g/cm2. The high molecular weight of curdlan had high gel strength.

Emergence of Antimicrobial-Resistant Escherichia coli of Animal Origin Spreading in Humans.

In the context of the great concern about the impact of human activities on the environment, we studied 403 commensal Escherichia coli/Escherichia clade strains isolated from several animal and human populations that have variable contacts to one another. Multilocus sequence typing (MLST) showed a decrease of diversity 1) in strains isolated from animals that had an increasing contact with humans and 2) in all strains that had increased antimicrobial resistance. A specific B1 phylogroup clonal complex (CC87, Institut Pasteur schema nomenclature) of animal origin was identified and characterized as being responsible for the increased antimicrobial resistance prevalence observed in strains from the environments with a high human-mediated antimicrobial pressure. CC87 strains have a high capacity of acquiring and disseminating resistance genes with specific metabolic and genetic determinants as demonstrated by high-throughput sequencing and phenotyping. They are good mouse gut colonizers but are not virulent. Our data confirm the predominant role of human activities in the emergence of antimicrobial resistance in the environmental bacterial strains and unveil a particular E. coli clonal complex of animal origin capable of spreading antimicrobial resistance to other members of microbial communities.

Enhanced in vivo fitness of carbapenem-resistant oprD mutants of Pseudomonas aeruginosa revealed through high-throughput sequencing.

An important question regarding the biologic implications of antibiotic-resistant microbes is how resistance impacts the organism's overall fitness and virulence. Currently it is generally thought that antibiotic resistance carries a fitness cost and reduces virulence. For the human pathogen Pseudomonas aeruginosa, treatment with carbapenem antibiotics is a mainstay of therapy that can lead to the emergence of resistance, often through the loss of the carbapenem entry channel OprD. Transposon insertion-site sequencing was used to analyze the fitness of 300,000 mutants of P. aeruginosa strain PA14 in a mouse model for gut colonization and systemic dissemination after induction of neutropenia. Transposon insertions in the oprD gene led not only to carbapenem resistance but also to a dramatic increase in mucosal colonization and dissemination to the spleen. These findings were confirmed in vivo with different oprD mutants of PA14 as well as with related pairs of carbapenem-susceptible and -resistant clinical isolates. Compared with OprD(+) strains, those lacking OprD were more resistant to killing by acidic pH or normal human serum and had increased cytotoxicity against murine macrophages. RNA-sequencing analysis revealed that an oprD mutant showed dramatic changes in the transcription of genes that may contribute to the various phenotypic changes observed. The association between carbapenem resistance and enhanced survival of P. aeruginosa in infected murine hosts suggests that either drug resistance or host colonization can cause the emergence of more pathogenic, drug-resistant P. aeruginosa clones in a single genetic event.

Oral antibiotic treatment induces skin microbiota dysbiosis and influences wound healing.

Antibiotic treatment eliminates commensal bacteria and impairs mucosal innate immune defenses in the gut. However, whether oral antibiotic treatment could alter the composition of the microbiota on the skin surface and influence innate immune responses remains unclear. To test this, mice were treated with vancomycin for 7 days and then wounds were made on the back skin of the mice. Five days later, scar tissue from each mouse was collected for bacterial enumeration, the bacterial composition on the scar and unwounded skin was determined using 16S RNA gene-based pyrosequencing analysis, and skin around wounds was collected for RNA extraction. Compared with the control group, the overall density and composition of skin bacteria were altered, and the proportion of Staphylococcus-related sequences was reduced in the vancomycin-treated group. Moreover, vancomycin treatment decreased the expression of RegIIIγ and interleukin (IL)-17 in the wounded skin. Taken together, our data demonstrate that antibiotic treatment decreases the bacterial density and alters the bacterial composition in skin wounds, followed by a decrease in RegIIIγ expression, which may contribute to the delayed wound repair. Our findings also indicate that antibiotic therapy should be carefully considered in the treatment of skin injury.

Okur-Chung neurodevelopmental syndrome: Implications for phenotype and genotype expansion.

BACKGROUND: Okur-Chung neurodevelopmental syndrome (OCNDS) is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1. It is characterized by intellectual disability, developmental delay, and multisystemic abnormalities. METHODS: We performed the whole-exome sequencing for a patient in a Chinese family. The co-segregation study using the Sanger sequencing method was performed among family members. Reverse transcription and quantitative real-time polymerase chain reaction were carried out using total RNA from blood samples of the proband and wild-type control subjects. A review of patients with OCNDS harboring CSNK2A1 pathogenic variants was conducted through a comprehensive search of the PubMed database. RESULTS: We identified a novel CSNK2A1 frameshift variant p.Tyr323Leufs*16 in a Chinese family. The proband, a 31-year-old female, presented with abnormal eating habits, recurrent seizures, language impairment, and intellectual disability. Her mother exhibited postnatal hernias, splenomegaly, and a predisposition to infections, but showed no significant developmental impairments or intellectual disability. Genetic studies revealed the presence of this variant in CSNK2A1 in both the proband and her mother. Transcription analysis revealed this variant may lead to nonsense-mediated mRNA decay, suggesting haploinsufficiency as a potential disease mechanism. We reviewed 47 previously reported OCNDS cases and discovered that individuals carrying CSNK2A1 null variants may exhibit a diminished frequency of symptoms linked to language deficits, dysmorphic facial features, or intellectual disability, consequently presenting an overall milder phenotype when compared to those with missense variants. CONCLUSION: We report a novel frameshift variant, p.Tyr323Leufs*16, in an OCNDS family with a generally mild phenotype. This study may broaden the spectrum of clinical presentations associated with OCNDS and contribute novel insights into the genotype-phenotype correlation of this condition.

Causal associations between Helicobacter Pylori infection and the risk and symptoms of Parkinson's disease: a Mendelian randomization study.

Background: Increasing evidence suggests an association between Helicobacter pylori (HP) infection and Parkinson's disease (PD) and its clinical manifestations, but the causal relationship remain largely unknown. Objective: To investigate the causal relationship between HP infection and PD risk, PD symptoms, and secondary parkinsonism, we conducted two-sample Mendelian randomization (MR). Methods: We obtained summary data from genome-wide association studies for seven different antibodies specific to HP proteins and five PD-related phenotypes. The inverse-variance weighted (IVW), weighted median, weighted mode, and MR-Egger methods were used to assess the causal relationships. Sensitivity analyses were performed to examine the stability of the MR results and reverse MR analysis was conducted to evaluate the presence of reverse causality. Results: Genetically predicted HP antibodies were not causally associated with an increased risk of PD. However, HP cytotoxin-associated gene-A (CagA) and outer membrane protein (OMP) antibody level were causally associated with PD motor subtype (tremor to postural instability/gait difficulty score ratio; ß = -0.16 and 0.46, P = 0.002 and 0.048, respectively). HP vacuolating cytotoxin-A (VacA) antibody level was causally associated with an increased risk of PD dementia [odds ratio (OR) = 1.93, P = 0.040]. Additionally, HP OMP antibody level was identified as a risk factor for drug-induced secondary parkinsonism (OR = 2.08, P = 0.033). These results were stable, showed no evidence of heterogeneity or directional pleiotropy, and no evidence of a reverse causal relationship. Conclusions: Our findings indicate that HP infection does not increase the risk of PD, but contributes to PD motor and cognitive symptoms. Different types of HP antibodies affect different symptoms of PD. Eradication of HP infection may help modulate and improve symptoms in PD patients.

Effects of Flammulina velutipes polysaccharide with ice recrystallization inhibition activity on the quality of beef patties during freeze-thaw cycles: An emphasis on water status and distribution.

The antifreeze activity of Flammulina velutipes polysaccharide (FVP) autoclave-extracted with dilute alkaline and effects of FVP on moisture status, size of ice crystals, physical and chemical characteristics of beef patties during repeated freeze-thaw (F-T) cycles were investigated. Results showed that FVP exhibited ice recrystallization inhibition activity and was able to alter the onset freezing/melting temperature of beef patties. 0.01% FVP significantly alleviated (P < 0.05) the decrement in water holding capacity by inhibiting water migration, restraining the mobility of water, and reducing the size of ice crystals of beef patties during the repeated F-T cycles. In addition, FVP could effectively inhibited oxidation reaction and protein aggregation of beef patties with significant decreases in TBARS value, protein turbidity, contents of total sulfhydryl and carbonyl of myofibrillar protein, and an increase in protein solubility during the repeated cycles. These results suggest FVP could be developed to be a promising cryoprotectant in frozen patties.

Vascular dysfunction in sporadic bvFTD: white matter hyperintensity and peripheral vascular biomarkers.

BACKGROUND: Vascular dysfunction was recently reported to be involved in the pathophysiological process of neurodegenerative diseases, but its role in sporadic behavioral variant frontotemporal dementia (bvFTD) remains unclear. The aim of this study was to systematically explore vascular dysfunction, including changes in white matter hyperintensities (WMHs) and peripheral vascular markers in bvFTD. METHODS: Thirty-two patients with bvFTD who with no vascular risk factors were enrolled in this cross-sectional study and assessed using positron emission tomography/magnetic resonance (PET/MRI) imaging, peripheral plasma vascular/inflammation markers, and neuropsychological examinations. Group differences were tested using Student's t-tests and Mann-Whitney U tests. A partial correlation analysis was implemented to explore the association between peripheral vascular markers, neuroimaging, and clinical measures. RESULTS: WMH was mainly distributed in anterior brain regions. All peripheral vascular factors including matrix metalloproteinases-1 (MMP-1), MMP-3, osteopontin, and pentraxin-3 were increased in the bvFTD group. WMH was associated with the peripheral vascular factor pentraxin-3. The plasma level of MMP-1 was negatively correlated with the gray matter metabolism of the frontal, temporal, insula, and basal ganglia brain regions. The WMHs in the frontal and limbic lobes were associated with plasma inflammation markers, disease severity, executive function, and behavior abnormality. Peripheral vascular markers were associated with the plasma inflammation markers. CONCLUSIONS: WMHs and abnormalities in peripheral vascular markers were found in patients with bvFTD. These were found to be associated with the disease-specific pattern of neurodegeneration, indicating that vascular dysfunction may be involved in the pathogenesis of bvFTD. This warrants further confirmation by postmortem autopsy. Targeting the vascular pathway might be a promising approach for potential therapy.

Purified protein glutaminase from Chryseobacterium proteolyticum enhances the properties of wheat gluten.

Protein glutaminase (PG), originating from Chryseobacterium proteolyticum, can catalyze the deamidation of glutamine residues in plant proteins into glutamic acid, thus enhancing its functional properties. However, the low yield of PG limits its industrial production. In this study, the yield of PG in C. proteolyticum TM1040 increased by 121 %, up to 7.30 U/mL in a 15 L fermenter after medium optimization. Subsequently, purified PG was obtained by cation exchange chromatography (CEX) coupled with hydrophobic interaction chromatography (HIC). The degree of deamidation (DD) of wheat gluten after purified PG deamidation was 87.11 %, which is superior to chemical deamidation in safety and DD. The emulsifying and foaming properties of deamidated wheat gluten were 2.67 and 18.86 times higher, and the water- and oil-holding properties were 4.23 and 18.77 times higher, respectively. The deamidated wheat gluten with enhanced functional properties was used to improve the flavor and texture in baking cakes.